EA044746B1 - ANTIBODIES AND ANTIGENS-BINDING FRAGMENTS AGAINST SARS-CoV-2 SPIKE GLYCOPROOTEIN - Google Patents

Description

List of sequences

An official copy of the sequence listing is provided simultaneously with the description of the invention in electronic form via EFS-Web in the form of a sequence listing in ASCII format with the file name 10753WO01-Sequence.txt, creation date June 25, 2020 and size 922462 bytes. The sequence listing contained herein in ASCII format is part of the specification and is incorporated herein by reference in its entirety.

Field of technology

The present invention relates to antibodies and antigen-binding fragments that specifically bind to coronavirus spike proteins, and methods for treating or preventing coronavirus infections using these antibodies and fragments.

State of the art

Newly identified viruses, such as coronaviruses, may be difficult to treat because they have not been sufficiently studied. The emergence of these newly identified viruses highlights the need to develop new antiviral strategies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged coronavirus that causes the severe acute respiratory disease COVID-19. SARS-CoV-2 was first identified in an outbreak in Wuhan, China, and as of March 20, 2020, the World Health Organization has reported 209,839 confirmed cases in 168 countries, regions, or territories, resulting in 8,778 deaths. Clinical signs of COVID-19 include fever, dry cough and fatigue, and the disease can cause respiratory failure, leading to death.

At the time of publication of this application, there was no vaccine or therapeutic agent to prevent or treat SARS-CoV-2 infection. Due to the ongoing threat to public health, there is an urgent need for prophylactic and therapeutic antiviral drugs to control SARS-CoV-2. Because this virus uses its spike glycoprotein to interact with the cellular receptor ACE2 and the serine protease TMPRSS2 to enter the target cell, this spike protein represents an attractive target for antibody therapy. In particular, fully human antibodies that specifically bind to the SARS-CoV-2-Spike protein (SARS-CoV-2-S) with high affinity and suppress the infectivity of the virus may be important for the prevention and treatment of COVID-19.

Brief description of the invention

There is a need for neutralizing therapeutic antibodies against the SARS-CoV-2 Spike protein (SARS-CoV-2-S) and their use for the treatment or prevention of viral infection. The present invention partially satisfies this need by providing human antibodies against SARS-CoV-2-S, for example, the antibodies from table. 1, and combinations thereof, including, for example, combinations with other therapeutic agents (eg, anti-inflammatory agents, antimalarial agents, antiviral agents, or other antibodies or antigen-binding moieties), and methods of using them to treat viral infections.

The present invention provides neutralizing human antigen-binding proteins that specifically bind to SARS-CoV-2-S, for example, antibodies or antigen-binding fragments thereof.

In one aspect of the present invention, there is provided an isolated recombinant antibody or antigen binding fragment thereof that specifically binds to the coronavirus spike protein (CoV-S), wherein said antibody has one or more of the following characteristics: (a) binds to CoV-S with an EC ₅₀ of less than approximately 10 ^-9 M; (b) demonstrates an increase in survival in a coronavirus-infected animal following administration to said coronavirus-infected animal compared to a comparable coronavirus-infected animal not exposed to said administration; and/or (c) contains three heavy chain complementarity determining regions (CDRs) (CDR-H1, CDR-H2 and CDR-H3) contained in a heavy chain variable region (HCVR) containing an amino acid sequence characterized by at least approximately 90% sequence identity with respect to HCVR from table. 1; and three light chain CDRs (CDR-L1, CDR-L2 and CDR-L3) contained in the light chain variable region (LCVR) containing an amino acid sequence having at least about 90% sequence identity to the LCVR of Table. 1.

In some embodiments, the antibody or antigen-binding fragment comprises: (a) an immunoglobulin heavy chain variable region comprising the CDR-H1, CDR-H2, and CDR-H3 antibodies of Table 1. 1; and/or (b) an immunoglobulin light chain variable region containing CDR-L1, CDR-L2 and CDR-L3 antibodies from table. 1.

In some embodiments, the antibody or antigen binding fragment comprises: (a) an immunoglobulin heavy chain variable region comprising an amino acid sequence having at least 90% amino acid sequence identity to the HCVR sequence of Table. 1; and/or (b) an immunoglobulin light chain variable region comprising an amino acid sequence having at least 90% amino acid sequence identity to the sequence

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LCVR from table. 1.

In some embodiments, the antibody or antigen binding fragment comprises CDRH1, CDR-H2, CdR-h3, CDR-L1, CDR-L2, and CDR-L3 of one antibody from Table 1. 1. In some embodiments, the antibody or antigen-binding fragment comprises an immunoglobulin containing

HCVR and LCVR of one antibody from the table. 1.

In one aspect of the present invention, an antigen binding protein is provided that competes with any of the antibodies or antigen binding fragments discussed above or herein for binding to CoV-S.

In one aspect of the present invention, an antigen binding protein is provided that binds to the same or overlapping epitope on CoV-S as any of the antibodies or antigen binding fragments discussed above or herein.

In any of various embodiments, the antibody or antigen binding fragment may be multispecific.

In any of various embodiments, the antibody or antigen binding fragment may have one or more of the following properties: a) inhibits the growth of a coronavirus; b) binds to the surface of the coronavirus; c) limits the spread of coronavirus infection in cells in vitro; and d) protects recombinant mice expressing human ACE2 or TMPRSS2 protein from death and/or weight loss caused by coronavirus infection.

In any of the various embodiments, the CoV-S is SARS-CoV-2-S.

In one aspect of the present invention, there is provided a complex comprising an antibody or antigen binding fragment discussed above or herein associated with a CoV-S polypeptide. In some embodiments, the CoV-S is SARS-CoV-2-S.

In one aspect of the present invention, there is provided a method of producing an antibody or antigen binding fragment described above or herein, comprising: (a) introducing into a host cell one or more polynucleotides encoding said antibody or antigen binding fragment; (b) culturing the host cell under conditions favorable for the expression of one or more polynucleotides; and (c) optionally, isolating the antibody or antigen-binding fragment from the host cell and/or the environment in which the host cell grows. In some embodiments, the host cell is a Chinese hamster ovary cell.

In one aspect of the present invention, an antibody or antigen binding fragment is provided as a product of the method discussed above.

In one aspect of the present invention, there is provided a polypeptide comprising: (a) CDR-H1, CDRH2 and CDR-H3 of the HCVR domain of an antibody or an antigen binding fragment containing the amino acid sequence of HCVR presented in table. 1; or (b) CDR-L1, CDR-L2 and CDR-L3 of the LCVR domain of an immunoglobulin chain containing the LCVR amino acid sequence shown in table. 1.

In one aspect of the present invention there is provided a polynucleotide encoding a polypeptide discussed above.

In one aspect of the present invention, a vector is provided containing the polynucleotide discussed above.

In one aspect of the present invention, there is provided a host cell comprising an antibody or antigen binding fragment or polypeptide or polynucleotide or vector discussed above or herein.

In one aspect, the present invention provides a composition or kit comprising an antibody or antigen binding fragment discussed above or herein in combination with an additional therapeutic agent.

In one aspect, the present invention provides a pharmaceutical composition comprising an antigen binding protein, antibody or antigen binding fragment discussed above or herein, a pharmaceutically acceptable carrier and, optionally, an additional therapeutic agent. In some embodiments, the additional therapeutic agent is an antiviral drug or vaccine. In some embodiments, the additional therapeutic agent is selected from the group consisting of: an anti-inflammatory agent, an anti-malarial agent, an antibody or antigen-binding fragment thereof that specifically binds to TMPRSS2, and an antibody or antigen-binding fragment thereof that specifically binds to CoV-S. In some cases, the antimalarial agent is chloroquine or hydroxychloroquine. In some cases, the anti-inflammatory agent is an antibody, such as sarilumab, tocilizumab, or gimsilumab. In some embodiments, the additional therapeutic agent is a second antibody or antigen binding fragment comprising the sequences HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 from Table. 1.

In one aspect of the present invention, there is provided an injectable vessel or article comprising an antigen binding protein, antibody or antigen binding fragment or composition discussed above or herein.

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In one aspect, the present invention provides a method of treating or preventing coronavirus infection in a subject in need thereof, comprising administering a therapeutically effective amount of an antigen binding protein, antibody, or antigen binding fragment discussed above or herein. In some embodiments, the coronavirus is selected from the group consisting of SARS-CoV-2, SARS-CoV, and MERS-CoV.

In some embodiments of a method of treating or preventing a coronavirus infection, one or more additional therapeutic agents are administered to a subject. In some cases, one or more of the additional therapeutic agents is an antiviral drug or vaccine. In some cases, one or more of the additional therapeutic agents is selected from the group consisting of: an anti-inflammatory agent, an anti-malarial agent, an antibody or antigen binding fragment thereof that specifically binds TMPRSS2, and an antibody or antigen binding fragment thereof that specifically binds CoV-S. In some cases, the antimalarial agent is chloroquine or hydroxychloroquine. In some cases, the anti-inflammatory agent is an antibody, such as sarilumab, tocilizumab, or gimsilumab. In some embodiments, the additional therapeutic agent is a second antibody or antigen binding fragment comprising the sequences HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 from Table. 1. Other antibodies that can be used alone or in combination with each other or with one or more antibodies described herein for use in the context of the methods of the present invention include, for example, LY-CoV555 (Eli Lilly); 47D11 (Wang et al., Nature Communications, article no. 2251); B38, H4, B5 and/or H2 (Wu et al., 10.1126/science.abc2241 (2020); STI-1499 (Sorrento Therapeutics); VIR-7831 and VIR7832 (Vir Biotherapeutics).

In one aspect, the present invention provides a method of administering an antibody or antigen binding fragment discussed above or herein to a subject, comprising injecting the antibody or antigen binding fragment into the subject. In some embodiments, the antibody or antigen binding fragment is administered to a subject subcutaneously, intravenously, or intramuscularly.

In any of the various embodiments discussed above or herein, the antibody or antigen binding fragment comprises a VH3-66 or Vk1-33 variable domain sequence.

In one aspect of the present invention, there is provided an isolated antibody or antigen binding fragment thereof that binds the SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, wherein said isolated antibody or antigen binding fragment comprises three complementarity determining regions (CDRs) heavy chain (HCDR1, HCDR2 and HCDR3) contained in a heavy chain variable region (HCVR) containing the amino acid sequence shown in SEQ ID NO: 202 and three light chain complementarity determining regions (CDRs) (LCDR1, LCDR2 and LCDR3) contained in a light chain variable region (LCVR) containing the amino acid sequence set forth in SEQ ID NO: 210.

In some embodiments, HCDR1 contains the amino acid sequence set forth in SEQ ID NO: 204, HCDR2 contains the amino acid sequence set forth in SEQ ID NO: 206, HCDR3 contains the amino acid sequence set forth in SEQ ID NO: 208, LCDR1 contains the amino acid sequence set forth in SEQ ID NO: 212, LCDR2 contains the amino acid sequence set forth in SEQ ID NO: 55, and LCDR3 contains the amino acid sequence set forth in SEQ ID NO: 214. In some embodiments, the isolated antibody or antigen binding fragment thereof comprises an HCVR comprising the amino acid sequence set forth in SEQ ID NO: 202. In some embodiments, the isolated antibody or antigen binding fragment thereof comprises an LCVR comprising an amino acid sequence set forth in SEQ ID NO: 210. In some embodiments, the isolated antibody or antigen binding fragment thereof comprises an HCVR comprising an amino acid sequence set forth in SEQ ID NO: 210. In some embodiments, the isolated antibody or antigen binding fragment thereof comprises an HCVR comprising an amino acid sequence set forth in presented in SEQ ID NO: 202, and LCVR containing the amino acid sequence presented in SEQ ID NO: 210.

In one aspect of the present invention, there is provided an isolated antibody that binds the SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, wherein the isolated antibody comprises an immunoglobulin constant region, three heavy chain complementarity determining regions (CDRs) ( HCDR1, HCDR2 and HCDR3), contained in the heavy chain variable region (HCVR), containing the amino acid sequence presented in SEQ ID NO: 202, and three light chain complementarity determining regions (CDRs) (LCDR1, LCDR2 and LCDR3), contained in light chain variable region (LCVR) containing the amino acid sequence set forth in SEQ ID NO: 210.

In some embodiments, HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 204, HCDR2 comprises the amino acid sequence set forth in

- 3 044746 in SEQ ID NO: 206, HCDR3 contains the amino acid sequence presented in SEQ ID NO: 208, LCDR1 contains the amino acid sequence presented in SEQ ID NO: 212, LCDR2 contains the amino acid sequence presented in SEQ ID NO: 55, a LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 214. In some embodiments, the isolated antibody comprises an HCVR comprising the amino acid sequence set forth in SEQ ID NO: 202 and an LCVR comprising the amino acid sequence set forth in SEQ ID NO: 210. B In some embodiments, the isolated antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 216 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 218. In some cases, the immunoglobulin constant region is an IgG1 constant region. In some cases, the isolated antibody is a recombinant antibody. In some cases, the isolated antibody is multispecific.

In one aspect of the present invention, there is provided a pharmaceutical composition comprising an isolated antibody discussed above or herein and a pharmaceutically acceptable carrier or diluent.

In some embodiments, the pharmaceutical composition further comprises a second therapeutic agent. In some cases, the second therapeutic agent is selected from the group consisting of: a second antibody or an antigen binding fragment thereof that binds the SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, an anti-inflammatory agent, an antimalarial agent, and an antibody or antigen-binding fragment that binds TMPRSS2.

In some embodiments, the second therapeutic agent is a second antibody or antigen binding fragment thereof that binds the SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832. In some cases, the second antibody or antigen binding fragment thereof comprises three CDRs of severe chains (HCDR1, HCDR2 and HCDR3) contained in HCVR containing the amino acid sequence presented in SEQ ID NO: 640, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained in LCVR containing the amino acid sequence presented in SEQ ID NO: 646. In some cases, the second antibody or antigen binding fragment thereof comprises: HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 642; HCDR2 containing the amino acid sequence presented in SEQ ID NO: 499; HCDR3, containing the amino acid sequence presented in SEQ ID NO: 644; LCDR1 containing the amino acid sequence presented in SEQ ID NO: 648; LCDR2 containing the amino acid sequence presented in SEQ ID NO: 650; and LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 652. In some cases, the second antibody or antigen binding fragment thereof comprises an HCVR comprising the amino acid sequence set forth in SEQ ID NO: 640 and an LCVR containing the amino acid sequence set forth in SEQ ID NO: 646. In some cases, the second antibody or antigen binding fragment thereof comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 654 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 656.

In one aspect of the present invention, there is provided an isolated antibody or antigen binding fragment thereof that binds the SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, wherein said isolated antibody or antigen binding fragment comprises three complementarity determining regions (CDRs) heavy chain (HCDR1, HCDR2 and HCDR3) contained in a heavy chain variable region (HCVR) containing the amino acid sequence shown in SEQ ID NO: 640 and three light chain complementarity determining regions (CDRs) (LCDR1, LCDR2 and LCDR3) contained in a light chain variable region (LCVR) containing the amino acid sequence set forth in SEQ ID NO: 646.

In some embodiments, HCDR1 contains the amino acid sequence set forth in SEQ ID NO: 642, HCDR2 contains the amino acid sequence set forth in SEQ ID NO: 499, HCDR3 contains the amino acid sequence set forth in SEQ ID NO: 644, LCDR1 contains the amino acid sequence set forth in SEQ ID NO: 648, LCDR2 contains the amino acid sequence set forth in SEQ ID NO: 650, and LCDR3 contains the amino acid sequence set forth in SEQ ID NO: 652. In some embodiments, the isolated antibody or antigen binding fragment thereof comprises an HCVR comprising the amino acid sequence set forth in SEQ ID NO: 640. In some embodiments, the isolated antibody or antigen binding fragment thereof comprises an LCVR comprising an amino acid sequence set forth in SEQ ID NO: 646. In some embodiments, the isolated antibody or antigen binding fragment thereof comprises an HCVR comprising an amino acid sequence set forth in SEQ ID NO: 646. In some embodiments, the isolated antibody or antigen binding fragment thereof comprises an HCVR comprising an amino acid sequence set forth in presented in SEQ ID NO: 640, and LCVR containing the amino acid sequence presented in SEQ ID NO: 646.

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In one aspect of the present invention, there is provided an isolated antibody that binds the SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, wherein the isolated antibody comprises an immunoglobulin constant region, three heavy chain complementarity determining regions (CDRs) ( HCDR1, HCDR2 and HCDR3), contained in the heavy chain variable region (HCVR), containing the amino acid sequence presented in SEQ ID NO: 640, and three light chain complementarity determining regions (CDRs) (LCDR1, LCDR2 and LCDR3), contained in light chain variable region (LCVR) containing the amino acid sequence set forth in SEQ ID NO: 646.

In some embodiments, HCDR1 contains the amino acid sequence set forth in SEQ ID NO: 642, HCDR2 contains the amino acid sequence set forth in SEQ ID NO: 499, HCDR3 contains the amino acid sequence set forth in SEQ ID NO: 644, LCDR1 contains the amino acid sequence set forth in SEQ ID NO: 648, LCDR2 contains the amino acid sequence set forth in SEQ ID NO: 650, and LCDR3 contains the amino acid sequence set forth in SEQ ID NO: 652. In some embodiments, the isolated antibody comprises an HCVR comprising the amino acid sequence set forth in SEQ ID NO: 640, and an LCVR comprising the amino acid sequence set forth in SEQ ID NO: 646. In some embodiments, the isolated antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 654 and a light chain comprising the amino acid sequence set forth in in SEQ ID NO: 656. In some cases, the immunoglobulin constant region is an IgG1 constant region. In some cases, the isolated antibody is a recombinant antibody. In some cases, the isolated antibody is multispecific.

In one aspect of the present invention, there is provided a pharmaceutical composition comprising an isolated antibody discussed above or herein and a pharmaceutically acceptable carrier or diluent.

In some embodiments, the pharmaceutical composition further comprises a second therapeutic agent. In some cases, the second therapeutic agent is selected from the group consisting of: a second antibody or an antigen binding fragment thereof that binds the SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, an anti-inflammatory agent, an antimalarial agent, and an antibody or antigen-binding fragment that binds TMPRSS2.

In some embodiments, the second therapeutic agent is a second antibody or antigen binding fragment thereof that binds the SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832. In some cases, the second antibody or antigen binding fragment thereof comprises three CDRs of severe chains (HCDR1, HCDR2 and HCDR3) contained in the HCVR containing the amino acid sequence presented in SEQ ID NO: 202, and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained in the LCVR containing the amino acid sequence presented in SEQ ID NO: 210. In some cases, the second antibody or antigen binding fragment thereof comprises: HCDR1 comprising the amino acid sequence set forth in SEQ ID NO: 204; HCDR2 containing the amino acid sequence presented in SEQ ID NO: 206; HCDR3, containing the amino acid sequence presented in SEQ ID NO: 208; LCDR1 containing the amino acid sequence presented in SEQ ID NO: 212; LCDR2 containing the amino acid sequence presented in SEQ ID NO: 55; and LCDR3 comprising the amino acid sequence set forth in SEQ ID NO: 214. In some cases, the second antibody or antigen binding fragment thereof comprises an HCVR comprising the amino acid sequence set forth in SEQ ID NO: 202 and an LCVR containing the amino acid sequence set forth in SEQ ID NO: 210. In some cases, the second antibody or antigen binding fragment thereof comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 216 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 218.

In various embodiments, any of the features or components of the embodiments discussed above or herein can be combined, and such combinations are within the scope of the present invention. Any particular value discussed above or herein may be combined with another related value discussed above or herein to denote a range in which said values represent upper and lower limits of the range, and such ranges are within the scope of the present invention.

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Brief description of drawings

In fig. Figure 1 shows blocking ELISA data for selected antibodies against

SARS-CoV-2-S against the SARS-CoV-2 spike protein, preventing the spike protein from binding to its receptor ACE2.

In fig. Figure 2 shows blocking ELISA data for selected anti-SARS-CoV-2-S antibodies against the SARS-CoV-2 spike protein, preventing the spike protein from binding to its receptor ACE2.

In fig. Figure 3 shows blocking ELISA data for selected anti-SARS-CoV-2-S antibodies against the SARS-CoV-2 spike protein, preventing the spike protein from binding to its receptor ACE2.

In fig. Figure 4 shows blocking ELISA data for selected anti-SARS-CoV-2-S antibodies against the SARS-CoV-2 spike protein, preventing the spike protein from binding to its receptor ACE2.

In fig. Figure 5 shows blocking ELISA data for selected anti-SARS-CoV-2-S antibodies against the SARS-CoV-2 spike protein, preventing the spike protein from binding to its receptor ACE2.

In fig. Figure 6 shows blocking ELISA data for selected anti-SARS-CoV-2-S antibodies against the SARS-CoV-2 spike protein, preventing the spike protein from binding to its receptor ACE2.

In fig. Figure 7 shows blocking ELISA data for selected anti-SARS-CoV-2-S antibodies against the SARS-CoV-2 spike protein, preventing the spike protein from binding to its receptor ACE2.

In fig. Figure 8 shows blocking ELISA data for selected anti-SARS-CoV-2-S antibodies against the SARS-CoV-2 spike protein, preventing the spike protein from binding to its receptor ACE2.

In fig. 9A and FIG. Figure 9B shows V gene frequencies for paired heavy (X-axis) and light (Y-axis) chains of isolated anti-SARS-CoV-2 neutralizing antibodies for VelocImmune® mice (Figure 9A; N=185) and convalescent human donors (Figure 9B ; N=68). The shade and size of the circle correspond to the number of heavy and light chain pairs present in the repertoire of isolated neutralizing antibodies. Neutralization was defined as >70% at a 1:4 antibody dilution (~2 μg/mL) in the VSV pseudoparticle neutralization assay.

In fig. 10A and FIG. 10B shows the neutralization efficiency. In fig. 10A shows the neutralization efficiency of mAbs against SARS-CoV-2 spikes. Serial dilutions of anti-spike mAbs, isotype control IgG1, and recombinant dimeric ACE2 (hACE2.hFc) were added with pVSVSARS-CoV-2-S-mNeon to Vero cells, and mNeon expression was measured 24 h postinfection as an indication of virus infectivity. Data are presented as percent neutralization relative to a challenge with virus alone. In fig. 10B shows the neutralization efficacy of individual anti-spike mAbs and combinations of anti-SARS-CoV-2-S mAbs in VeroE6 cells.

In fig. 11 shows an epitope pooling analysis based on a matrix of binding assays of a preformed mixture of different anti-SARS-CoV-2 mAbs. Epitope pooling was performed against nine reported SARS-CoV-2 mAbs. For each plot, three phases (I, II and III) were presented. In phase I, anti-SARS-CoV-2 mAb (20 μg/ml) was loaded into an anti-human Fc probe. In phase II, a solution of human IgG1 blocking antibodies (100 μg/ml). In phase III, a solution of 100 nM complex of the preformed SARS CoV-2 RBD-MMH mixture and 600 nM mAb against each SARS-CoV2 binding site was flowed through the mAb capture probe.

In fig. Figure 12 shows a three-dimensional surface model of the spike protein RBD domain structure, showing the region of interaction with ACE2 and the results of HDX-MS epitope mapping. RBD residues protected by antibodies against SARS-CoV2 spikes are indicated by shading, which reflects the degree of protection determined in HDX-MS experiments. The RBD structure is based on PDB 6M17.

In fig. 13A and FIG. 13B shows the complex of mAb10933 and mAb10987 with the SARS-CoV-2 RBD. In fig. 13A shows a 3.9 A cryoEM map of the mAb10933+RBD+mAb10987 complex, shaded according to the chains in the refined model in FIG. 13B. The RBD, heavy and light chains of mAb10933, and the heavy and light chains of mAb10987 were detected.

In fig. Figure 14 shows the statistics of the cryoEM data. Data collection and refinement statistics are presented for the structure of the mAb10987+mAb10933+RBD SARS-CoV-2 complex shown in FIG. 13A and FIG. 13B.

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Detailed Description of the Invention

Before describing the methods of the present invention, it should be understood that the present invention is not limited to the specific methods and experimental conditions described, since such methods and conditions may vary. It should also be understood that the terminology used herein is intended solely to describe certain embodiments and should not be construed as limiting, since the scope of the present invention is limited only by the appended claims.

Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly used by those skilled in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein may be used in the practice or testing of the present invention, preferred methods and materials are described herein. All publications referred to herein are incorporated herein by reference in their entirety.

The term coronavirus or CoV refers to any virus of the coronavirus family, including but not limited to SARS-CoV-2, MERS-CoV and SARS-CoV. SARS-CoV-2 refers to a newly emerged coronavirus identified as the cause of a serious outbreak that began in Wuhan, China, and is rapidly spreading to other areas of the globe. SARS-CoV-2 is also known as 2019-nCoV coronavirus and Wuhan coronavirus. It binds via the viral spike protein to the host cell's angiotensin-converting enzyme 2 (ACE2) receptor. The spike protein also binds to TMPRSS2, which cleaves the spike protein and activates virus-membrane fusion.

The term CoV-S, also known as S or S protein, refers to the spike protein of the coronavirus and can refer to a specific S protein, such as SARS-CoV-2-S, MERS-CoV S and SARS-CoV S. Spike protein SARS-CoV-2 is a type I membrane glycoprotein consisting of 1273 amino acids that assembles into trimers that constitute the spikes or peplomers on the surface of the enveloped coronavirus particle. This protein has two main functions: host receptor binding and membrane fusion, which are attributed to the N-terminal (S1) and C-terminal (S2) halves of the S protein. CoV-S binds to its receptor through the receptor binding domain (RBD) present in the S1 subunit. The amino acid sequence of the full-length SARS-CoV-2 spike protein is represented by the amino acid sequence given in SEQ ID NO: 832. The term CoV-S includes variants of the CoV spike protein isolated from various CoV isolates, as well as recombinant CoV spike protein or a fragment thereof. The term also includes the CoV spike protein or a fragment thereof associated with, for example, a histidine tag, a mouse or human Fc, or a signal sequence, such as ROR1.

The term coronavirus infection or CoV infection as used herein refers to an infection with a coronavirus, such as SARS-CoV-2, MERS-CoV or SARS-CoV. This term includes coronavirus infections of the respiratory tract, often the lower respiratory tract. Symptoms may include high fever, dry cough, shortness of breath, pneumonia, gastrointestinal symptoms such as diarrhea, organ failure (kidney failure and renal dysfunction), septic shock and, in severe cases, death.

Viruses.

The present invention includes methods for treating or preventing a viral infection in a subject. The term virus includes any virus whose infection in a subject is treatable or preventable by administration of an antibody against CoV-S or an antigen-binding fragment thereof (eg, where the infectivity of the virus is at least partially dependent on CoV-S). In one embodiment of the present invention, the virus is any virus that expresses the spike protein (eg, CoV-S). The term virus also includes a CoV-S-dependent respiratory virus, which is a virus that infects the tissue of a subject's respiratory organs (eg, upper and/or lower respiratory tract, trachea, bronchi, lungs) and is treatable or preventable by administration of an anti-CoV antibody -S or its antigen-binding fragment. For example, in one embodiment of the present invention, the virus includes the coronavirus, SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), SARS-CoV (severe acute respiratory syndrome coronavirus) and MERS-CoV (Middle East respiratory syndrome coronavirus (MERS) ). Coronaviruses may include the genera alphacoronaviruses, betacoronaviruses, gammacoronaviruses, and deltacoronaviruses. In some embodiments, antibodies or antigen binding fragments provided herein can bind to and/or neutralize alpha coronavirus, beta coronavirus, gamma coronavirus, and/or delta coronavirus. In some embodiments, this binding and/or neutralization may be specific to a particular genus of coronaviruses or to a particular subset of genera. Viral infection refers to the invasion and replication of a virus in a subject's body.

Coronavirus virions are spherical in shape with a diameter of approximately 125 nm. Most ha

- 7 044746 A characteristic feature of coronaviruses is the club-shaped spikes on the surface of the virion. These spikes are the defining feature of the virion and give it the appearance of a solar corona, hence the name coronaviruses. Inside the virion shell is a nucleocapsid. Coronaviruses contain helical symmetric nucleocapsids, which is unusual for positive-sense RNA viruses but is much more common in negative-sense RNA viruses. SARS-CoV-2, MERS-CoV and SARS-CoV belong to the coronavirus family. The initial attachment of the virion to the host cell is initiated by interactions between the S protein and its receptor. Receptor binding domain (RBD) sites in the S1 region of the coronavirus S protein vary among viruses, with some containing an RBD at the C terminus of S1. The S protein/receptor interaction is a major determinant of the ability of a coronavirus to infect a host species and also determines the tissue tropism of the virus. Many coronaviruses use peptidases as cellular receptors. Once the receptor binds, the virus must gain access to the cytosol of the host cell. This is typically achieved through acid-dependent proteolytic cleavage of the S protein by cathepsin, TMPRRS2, or another protease, followed by fusion of the viral and cellular membranes.

Antibodies and antigen-binding fragments against CoV-S.

The present invention provides antigen-binding proteins, for example, antibodies and antigen-binding fragments thereof that specifically bind to the CoV spike protein or an antigenic fragment thereof.

As used herein, the term antibody refers to immunoglobulin molecules containing four polypeptide chains—two heavy chains (HC) and two light chains (LC) linked by disulfide bonds (i.e., complete antibody molecules), as well as multimers thereof (e.g., IgM ). Examples of antibodies include, for example, the antibodies listed in table. 1. Each heavy chain contains a heavy chain variable region (HCVR or _VH ) and a heavy chain constant region (consisting of CH1, CH2 and CH3 domains). Each light chain consists of a light chain variable region (LCVR or VL) and a light chain constant region ( _CL ). The VH and V _L regions can further be distinguished by regions of hypervariability called complementarity determining regions (CDRs), which are separated by more conserved regions called framework regions (FRs). Each V _H and V _L contains three CDRs and four FRs, arranged from N-terminus to C-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The heavy chain CDR may also be referred to as HCDR or CDR-H and numbered as described above (eg, HCDR1, HCDR2 and HCDR3 or CDR-H1, CDR-H2 and CDR-H3). Likewise, the light chain CDRs may be referred to as LCDR or CDR-L and may be numbered LCDR1, LCDR2 and LCDR3 or CDR-L1, CDR-L2 and CDR-L3. In some embodiments of the present invention, the FR antibody (or antigen binding fragment thereof) is identical to human germline sequences or modified naturally or artificially. Examples of human germline sequences include, but are not limited to, VH3-66 and Vk1-33. Thus, the present invention provides antibodies against CoV-S or antigen binding fragments thereof (for example, antibodies against SARS-CoV-2-S or antigen binding fragments thereof) containing the HCDR and LCDR sequences from table. 1 within the heavy or light chain variable region of VH3-66 or Vk1-33. In addition, the present invention provides antibodies against CoV-S or antigen binding fragments thereof (for example, antibodies against SARS-CoV-2-S or antigen binding fragments thereof) containing the HCDR and LCDR sequences from table. 1 in combination light chain selected from IgKV4-1, IgKV 1-5, IgKV1-9, IgKV1-12, IgKV3-15, IgKV1-16, IgKV1-17, IgKV3-20, IgLV321, IgKV2-24, IgKV1-33 , IgKV1-39, IgLV1-40, IgLV1-44, IgLV1-51, IgLV3-1, IgKV1-6, IgLV2-8, IgKV3-11, IgLV2-11, IgLV2-14, IgLV2-23 or IgLV6-57, and heavy chain selected from gHV1-69, IgHV3-64, IgHV459, IgHV3-53, IgHV3-48, IgHV4-34, IgHV3-33, IgHV3-30, IgHV3-23, IgHV3-20, IgHV1-18, IgHV3-15 , IgHV3-11, IgHV3-9, IgHV1-8, IgHV3-7, IgHV2-5, IgHV1-2, IgHV2-70, IgHV3-66, IgHV5-51, IgHV1-46, IgHV4-39, IgHV4-31, IgHV3 -30-3, IgHV2-26 or IgHV7-4-1. In addition, the present invention provides antibodies against CoV-S or antigen binding fragments thereof (for example, antibodies against SARS-CoV-2-S or antigen binding fragments thereof) containing the HCVR and LCVR sequences from table. 1 in combination light chain selected from IgKV4-1, IgKV 1-5, IgKV1-9, IgKV1-12, IgKV315, IgKV1-16, IgKV1-17, IgKV3-20, IgLV3-21, IgKV2-24, IgKV1-33 , IgKV1-39, IgLV1-40, IgLV1-44, IgLV1-51, IgLV3-1, IgKV1-6, IgLV2-8, IgKV3-11, IgLV2-11, IgLV2-14, IgLV2-23 or IgLV6-57, and heavy chain selected from gHV1-69, IgHV3-64, IgHV4-59, IgHV3-53, IgHV3-48, IgHV4-34, IgHV3-33, IgHV3-30, IgHV3-23, IgHV3-20, IgHV1-18, IgHV3 -15, IgHV3-11, IgHV3-9, IgHV1-8, IgHV3-7, IgHV2-5, IgHV1-2, IgHV2-70, IgHV3-66, IgHV5-51, IgHV1-46, IgHV4-39, IgHV4-31 , IgHV3-30-3, IgHV2-26 or IgHV7-4-1.

Typically, the variable domains of both the heavy and light chains of an immunoglobulin contain three hypervariable regions, also called complementarity determining regions (CDRs), located within relatively conserved framework regions (FRs). Typically, the variable domains of both the light and heavy chains contain from N-terminus to C-terminus FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. In an embodiment of the present invention, the assignment of amino acids to each domain follows the definitions of Sequences of Proteins of Immunological Interest, Kabat, et al.; National Institutes of Health, Bethesda, Md.; 5 ^th ed.; NIH Publ. No. 91-3242 (1991); Kabat (1978) Adv. Prot.

- 8 044746

Chem. 32:1-75; Kabat, et al., (1977) J. Biol. Chem. 252:6609-6616; Chothia, et al., (1987) J Mol. Biol. 196:901917 or Chothia, et al., (1989) Nature 342:878-883.

The present invention provides monoclonal antigen binding proteins against CoV-S, for example, antibodies and antigen binding fragments thereof, as well as monoclonal compositions containing a plurality of isolated monoclonal antigen binding proteins. As used herein, the term monoclonal antibody refers to a population of essentially homogeneous antibodies, i.e. The antibody molecules that make up the population are identical in amino acid sequence, except for possible naturally occurring mutations that may be present in minute quantities. The plurality of such monoclonal antibodies and fragments in a composition refers to a concentration of identical (i.e., as discussed above, identical in amino acid sequence, excluding possible naturally occurring mutations that may be present in minute quantities) antibodies and fragments greater than the concentration typically occurring naturally, for example in the blood of a host organism, such as a mouse or a human.

In one embodiment of the present invention, an anti-CoV-S antigen binding protein, e.g., an antibody or antigen binding fragment, comprises a heavy chain constant domain, e.g., of the IgA type (e.g., IgA1 or IgA2), IgD, IgE, IgG (e.g., IgG1, IgG2, IgG3 and IgG4) or IgM. In an embodiment of the present invention, the antigen binding protein, eg, antibody or antigen binding fragment, comprises a light chain constant domain, eg, kappa or lambda type.

As used herein, the term antigen binding protein, e.g., human antibody or antigen binding fragment, includes antibodies and fragments containing variable and constant regions derived from human germline immunoglobulin sequences in a human cell or transplanted into a non-human cell, such as a mouse cell . See, for example, US8502018, US6596541 or US5789215. The human mAbs of the present invention may contain amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or somatic mutation in vivo), for example, in the CDR and, in particular, in CDR3. However, as used herein, the term human antibody is not intended to include mAbs in which CDR sequences derived from the germ line of other mammalian species (eg, mouse) are grafted onto human FR sequences. The term includes antibodies produced recombinantly in the body of a non-human mammal or in the cells of a non-human mammal. The term is not intended to include antibodies isolated from or obtained from a human subject. See below.

The present invention includes chimeric antigen binding proteins against CoV-S, for example, antibodies and antigen binding fragments thereof, and methods of using them. As used herein, the term chimeric antibody is an antibody comprising the variable domain of a first antibody and the constant domain of a second antibody, wherein the first and second antibodies are derived from different animal species (US4816567; and Morrison et al., (1984) Proc. Natl. Acad. Sci USA 81:6851-6855).

The present invention includes fusion antigen binding proteins against CoV-S, for example, antibodies and antigen binding fragments thereof, and methods of using them. As used herein, the term hybrid antibody is an antibody comprising a variable domain of a first antibody and a constant domain of a second antibody, wherein the first and second antibodies are derived from different animals, or the variable domain (but not the constant region) is derived from the first animal. For example, a variable domain can be taken from an antibody isolated from a human body and expressed with a fixed constant region not isolated from that antibody. Exemplary fusion antibodies are described in Example 1, which refers to PCR products derived from the heavy chain variable region and the light chain variable region of an antibody cloned into expression vectors containing a heavy chain constant region and a light chain constant region, respectively. Hybrid antibodies are synthetic and do not occur in nature because the variable and constant regions they contain are not isolated from a single natural source.

The term recombinant antigen-binding proteins, e.g., antibodies or antigen-binding fragments thereof, refers to such molecules generated, expressed, isolated or produced using technologies or methods known in the art, for example, recombinant DNA technology, which includes, for example, DNA splicing and transgene expression. The term includes antibodies expressed in a non-human mammal (including transgenic non-human mammals, e.g., transgenic mice), or in a cell-based (e.g., CHO cell-based) expression system, or in a cell-based expression system. cells that are not human cells, or isolated from a combinatorial library of recombinant human antibodies. In some embodiments, the recombinant antibody shares a common sequence with an antibody isolated from an organism (eg, mouse or human) but expressed through recombinant DNA technology. Such antibodies may include post-translational modifications (eg, glycosylation) that are different from those of the antibody isolated from the body.

Recombinant antigen binding proteins against CoV-S, such as the antibodies and antigen binding fragments described herein, can also be produced in the E. coli/T7 expression system. In this embodiment, nucleic acids encoding anti-CoV-S immunoglobulin molecules of the present invention (eg, those shown in Table 1) can be inserted into a pET-based plasmid and expressed in the E. coli/T7 system. For example, the present invention includes methods for expressing an antibody or an antigen binding fragment thereof or an immunoglobulin chain thereof in a host cell (e.g., a bacterial host cell, e.g., E. coli, e.g., BL21 or BL21DE3), comprising expressing T7 RNA polymerase in the cell, which also contains a polynucleotide encoding an immunoglobulin chain operably linked to the T7 promoter. For example, in an embodiment of the present invention, a bacterial host cell, such as E. coli, contains a polynucleotide encoding a T7 RNA polymerase gene operably linked to a lac promoter, and expression of the polymerase and chain is induced by incubating the host cell with IPTG (isopropyl beta -D-thiogalactopyranoside). See US4952496 and US5693489 or Studier & Moffatt, Use of bacteriophage T7 RNA polymerase to direct selective high-level expression of cloned genes, J. Mol. Biol. 1986 May 5;189(1):113-30.

There are several methods for producing recombinant antibodies known in the art. One example of a method for recombinant antibody production is described in US4816567.

Transformation can be accomplished by any known method of introducing polynucleotides (eg, DNA or RNA, including mRNA) into a host cell. Methods for introducing heterologous polynucleotides into mammalian cells are well known in the art and include dextran-mediated transfection, calcium phosphate precipitation, polybrene-mediated transfection, protoplast fusion, electroporation, liposome encapsulation of polynucleotide(s), lipid nanoparticle technology, biolistic injection, and direct microinjection of DNA into nuclei. In addition, nucleic acid molecules can be introduced into mammalian cells using viral vectors, such as lentivirus or adeno-associated virus. Methods for transforming cells are well known in the art. See, for example, US Pat. No. 4,399,216; 4912040; 4,740,461 and 4,959,455. In some embodiments, an antibody or antigen-binding fragment thereof of the present invention may be administered to a subject in the form of a nucleic acid (e.g., DNA or RNA, including mRNA) such that the subject's own cells produce the antibody. The present invention further provides modifications to the nucleotide sequences encoding the anti-CoV-S antibodies described herein that result in increased antibody expression, increased antibody stability, increased stability of nucleic acids (e.g., mRNA), or increased affinity or specificity of antibodies against the spike protein CoV.

Thus, the present invention includes recombinant methods for producing an antigen binding protein against CoV-S, for example, an antibody or an antigen binding fragment thereof according to the present invention, or an immunoglobulin chain thereof, comprising (i) introducing one or more polynucleotides (for example, containing the nucleotide sequence of any one or more sequences from Table 2) encoding light and/or heavy immunoglobulin chains or CDRs of antigen-binding protein, for example, from Table. 1, wherein the polynucleotide is located in the vector and/or is integrated into the chromosome of the host cell and/or is operably linked to a promoter; (ii) culturing a host cell (eg, CHO or Pichia or Pichia pastoris) under conditions favorable for expression of the polynucleotide, and (iii) optionally isolating the antigen binding protein (eg, antibody or fragment) or chain from the host cell and/or medium , in which the host cell grows. For example, a polynucleotide can be inserted into a host cell chromosome through targeted insertion using a vector, such as an adeno-associated virus (AAV), for example, after chromosome segregation using a gene editing system (eg, CRISPR (eg, CRISPR-Cas9), TALEN, megaTAL , zinc finger domain protein or Argonaute protein). Targeted insertions may occur, for example, in host cell loci, such as the genomic albumin or immunoglobulin locus. Alternatively, the insertion may take place at a random locus, for example using a vector such as a lentivirus. When creating an antigen-binding protein (e.g., an antibody or antigen-binding fragment) containing more than one immunoglobulin chain, for example, an antibody containing two immunoglobulin heavy chains and two immunoglobulin light chains, co-expression of the chains in the same host cell results in association of the chains, e.g. cell or on the surface of a cell or extracellularly, if such chains are secreted, to form an antigen-binding protein (eg, an antibody or antigen-binding fragment). Methods include methods in which only the immunoglobulin heavy chain or only the immunoglobulin light chain is expressed (eg, any chain described herein, including mature fragments and/or variable domains thereof). Such chains are useful, for example, as intermediates in the expression of an antibody or antigen-binding fragment containing such a chain. As an example, the present invention also includes antigen-binding proteins against CoV-S, for example, antibodies and antigen-binding fragments thereof containing an immunoglobulin heavy chain (or a variable domain thereof, or a domain containing a CDR thereof) encoded by a polynucleotide containing a nucleotide sequence presented in table. 2, and an immunoglobulin light chain (or its variable domain, or a domain containing its CDR) encoded by the nucleotide sequence presented in table. 2, which are the product of such preparation methods and, optionally, the set of purification methods presented herein. For example, in some embodiments, the product of the method is an anti-CoV-S antigen binding protein that is an antibody or fragment comprising an HCVR containing the amino acid sequence set forth in Table. 1, and LCVR containing the amino acid sequence presented in table. 1, with the HCVR and LCVR sequences selected from the same antibody shown in table. 1. In some embodiments, the product of the method is an anti-CoV-S antigen binding protein, which is an antibody or fragment comprising HCDR1, HCDR2 and HCDR3 containing the amino acid sequences presented in table. 1, and LCDR1, LCDR2 and LCDR3, containing the amino acid sequences presented in table. 1, and these six CDR sequences are selected from one antibody shown in table. 1. In some embodiments, the product of the method is an anti-CoV-S antigen binding protein, which is an antibody or fragment containing a heavy chain containing the amino acid sequence HC presented in table. 1, and a light chain containing the amino acid sequence LC, presented in table. 1.

Eukaryotic and prokaryotic host cells, including mammalian cells, can be used as hosts for the expression of antigen binding protein against CoV-S. Such host cells are well known in the art, and many are available from the American Type Culture Collection (ATCC). These host cells include, but are not limited to, Chinese hamster ovary (CHO) cells, NS0 cells, SP2 cells, HeLa cells, baby hamster kidney (BHK) cells, monkey kidney (COS) cells, human hepatocellular carcinoma cells (eg, Hep G2), A549 cells, 3T3 cells, HEK-293 cells and a number of other cell lines. Mammalian host cells include human, mouse, rat, dog, monkey, pig, goat, bovine, equine and hamster cells. Other cell lines that can be used are insect cell lines (eg Spodoptera frugiperda or Trichoplusia ni), amphibian cells, bacterial cells, plant cells and fungal cells. Fungal cells include cells of yeasts and filamentous fungi, including, for example, Pichia pastoris, Pichia finlandica, Pichia trehalophila, Pichia koclamae, Pichia membranaefaciens, Pichia minuta (Ogataea minuta, Pichia lindneri), Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia sp., Saccharomyces cerevisiae, Saccharomyces sp., Hansenula polymorpha, Kluyveromyces sp., Kluyveromyces lactis, Candida albicans, Aspergillus nidulans, Aspergillus niger, Aspergillus oryzae, Trichoderma re esei, Chrysosporium lucknowense, Fusarium sp., Fusarium gramineum, Fusarium venenatum, Physcomitrella patens and Neurospora crassa. The present invention includes an isolated host cell (eg, a CHO cell) containing an antigen binding protein, such as those listed in table. 1; or a polynucleotide encoding such a polypeptide.

The term specifically binds refers to antigen-binding proteins (e.g., mAbs) having a binding affinity for an antigen, e.g., CoV-S protein (e.g., SARS-CoV-2-S), expressed as a KD of at least about 10 ^-8 M, as measured in a real-time label-free biolayer interferometry assay, e.g. at 25°C or 37°C, e.g. using the Octet® HTX biosensor, or using surface plasmon resonance, e.g. BIACORE™, or using solid phase ELISA , which measures the affinity in a solution. The present invention includes antigen binding proteins that specifically bind to the CoV-S protein.

As used herein, the terms antigen binding portion or antigen binding fragment of an antibody or antigen binding protein and the like. include any naturally occurring, enzymatically produced, synthetic or genetically engineered polypeptide or glycoprotein that specifically binds an antigen to form a complex. Non-limiting examples of antigen binding fragments include: (i) Fab fragments; (ii) F(ab') ₂ -fragments; (iii) Fd fragments; (iv) Fv fragments; (v) single chain Fv molecules (scFv); (vi) dAb fragments; and (vii) minimal recognition units consisting of amino acid residues mimicking the hypervariable region of an antibody (eg, a dedicated complementarity determining region (CDR), e.g., CDR3 peptide), or a FR3-CDR3-FR4 peptide with limited conformational freedom. The expression antigen-binding fragment as used herein also includes other genetically modified molecules, e.g., domain-specific antibodies, single-domain antibodies, domain-deleted antibodies, chimeric antibodies, CDR-transplanted antibodies, diabodies, tri-bodies, tetrabodies, minibodies, nanobodies (e.g., monovalent nanobodies , divalent nanobodies, etc.), immunopharmaceuticals based on small modular protein (SMTP) and shark IgNAR variable domains. In one embodiment of the present invention, the antigen binding fragment contains three or more CDR antibodies from the table. 1 (for example, CDR-H1, CDR-H2 and CDR-H3; or

CDR-L1, CDR-L2 and CDR-L3).

In one embodiment of the present invention, the antigen binding fragment of the antibody typically contains at least one variable domain. The variable domain can be of any size or amino acid composition and typically contains at least one CDR that is adjacent to or in frame with one or more framework sequences. In antigen binding fragments containing a VH domain associated with a VL domain, the VH and VL domains may be located relative to each other in any suitable relationship. For example, the variable region may be dimeric and contain V _H - VH -, V _H - V _L - or V _L - V _L dimers. Alternatively, the antigen binding fragment of the antibody may contain a monomeric VH or VL domain.

In some embodiments, the antigen binding fragment of an antibody may comprise at least one variable domain covalently linked to at least one constant domain. Non-limiting exemplary variable and constant domain configurations that may be contained in an antigen binding fragment of an antibody of the present invention include: (i) Vh-Ch1; (ii) Vh-Ch2; (iii) Vh-Ch3; (iv) Vh-Ch1-Ch2; (v) Vh-Ch1-Ch2-Ch3; (vi) Vh-Ch2-Ch3; (vii) Vh-Cl; (viii) Vl-Ch1; (ix) Vl-Ch2; (x) Vl-Ch3; (xi) Vl-Ch1-Ch2; (xii) Vl-Ch1-Ch2-Ch3; (xiii) Vl-Ch2C _h 3; and (xiv) V _l -C _l . In any configuration of variable and constant domains, including any of the typical configurations listed above, the variable and constant domains may be directly linked to each other or may be linked through a full or partial hinge or linker region. The hinge region may consist of at least 2 (eg, 5, 10, 15, 20, 40, 60 or more) amino acids, resulting in a flexible or semi-flexible connection between adjacent variable and/or constant domains in a single polypeptide molecule. In addition, the antigen binding fragment of an antibody of the present invention may comprise a homodimer or heterodimer (or other multimer) in any of the variable and constant domain configurations listed above, non-covalently linked to each other and/or to one or more monomeric V _H or V _L - domains (eg via disulfide bond(s)).

Antigen-binding proteins (eg, antibodies and antigen-binding fragments) can be monospecific or multispecific (eg, bispecific). Multispecific antigen binding proteins are discussed further herein.

In specific embodiments, an antibody or antibody fragments of the present invention may be conjugated to a group such as a ligand or therapeutic group (immunoconjugate), such as an antiviral drug, an anti-influenza second antibody, or any other therapeutic group that can be used to treat a viral infection, for example, influenza virus infections. See below.

The present invention also provides a complex containing an anti-CoV-S antigen binding protein, such as an antibody or antigen binding fragment discussed herein, in complex with a CoV-S polypeptide or antigenic fragment thereof and/or a secondary antibody or antigen binding fragment thereof (eg , a secondary antibody labeled with a detectable label) that specifically binds to an anti-CoV-S antibody or fragment. In an embodiment of the present invention, said antibody or fragment is in vitro (eg, immobilized on a solid substrate) or in the body of a subject. In an embodiment of the present invention, CoV-S is located in vitro (eg, immobilized on a solid substrate) or on the surface of the virus, or in the body of the subject. Immobilized anti-CoV-S antibodies and antigen-binding fragments thereof covalently bound to an insoluble matrix material (eg, glass or polysaccharide, eg, agarose or sepharose, eg, a bead or other particle thereof) are also included in the present invention; wherein the immobilized antibody optionally forms a complex with CoV-S or an antigenic fragment thereof or a secondary antibody or fragment thereof.

Isolated antigen binding proteins (eg, antibodies or antigen binding fragments thereof), polypeptides, polynucleotides and vectors are at least partially free of other biological molecules present in the cells or cell culture from which they are derived. Such biological molecules include nucleic acids, proteins, other antibodies or antigen-binding fragments, lipids, carbohydrates or other material, such as cellular debris and growth media. The isolated antibody or antigen binding fragment may further be at least partially free of components of the expression system, such as biological molecules from the host cell or growth medium. Generally, the term isolated is not intended to denote the complete absence of such biological molecules or the absence of water, buffers or salts, or components of the pharmaceutical composition containing antibodies or fragments.

The term epitope refers to an antigenic determinant (eg, a CoV-S polypeptide) that interacts with a specific antigen-binding site of an antigen-binding protein, such as a variable region of an antibody molecule known as a paratope. One antigen may contain

- 12 044746 more than one epitope. Thus, different antibodies may bind to different regions on the antigen and may have different biological effects. The term epitope also refers to a site on an antigen to which B and/or T cells respond. It also refers to the region of an antigen that is bound by an antibody. Epitopes can be defined as structural or functional. Functional epitopes are typically a subset of structural epitopes and contain residues that directly determine the affinity of the interaction. Epitopes can also be conformational, i.e. consist of a non-linear sequence of amino acids. In certain embodiments, epitopes may include determinants that are chemically active surface moieties of molecules, such as amino acids, carbohydrate side chains, phosphoryl groups, or sulfonyl groups, and, in some embodiments, may have specific three-dimensional structure characteristics and/or specific charge characteristics .

Methods for determining the epitope of an antigen binding protein, such as an antibody or fragment or polypeptide, include mutational analysis by alanine scanning, peptide blot analysis (Reineke (2004) Methods Mol. Biol. 248: 443-63), peptide digestion analysis, crystallographic studies and NMR -analysis. In addition, methods such as epitope removal, epitope extraction, and chemical modification of antigens can be used (Tomer (2000) Prot. Sci. 9: 487-496). Another method that can be used to identify amino acids in a polypeptide with which an antigen binding protein (eg, antibody or fragment or polypeptide) (eg, coversin) interacts is hydrogen-deuterium exchange detected by mass spectrometry. In general terms, the hydrogen-deuterium exchange method involves labeling a protein of interest with deuterium and then coupling an antigen-binding protein, such as an antibody or fragment or polypeptide, to the deuterium-labeled protein. The CoV-S protein/antigen-binding protein complex is then transferred to water, and the exchanged protons within the amino acids protected by the antibody complex undergo back-deuterium-hydrogen exchange at a slower rate than the exchanged protons within amino acids not part of the interaction region. As a result, amino acids that are part of the protein/antigen-binding protein interaction region may retain deuterium and therefore exhibit relatively increased mass compared to amino acids that are not part of the interaction region. After dissociation of the antigen binding protein (eg, antibody or fragment or polypeptide), the target protein is subjected to protease digestion and mass spectrometric analysis, thereby identifying deuterium-labeled residues that correspond to the specific amino acids with which the antigen binding protein interacts. See, for example, Ehring (1999) Analytical Biochemistry 267: 252-259; Engen and Smith (2001) Anal. Chem. 73:256A265A.

As used herein, the term compete refers to an antigen binding protein (eg, an antibody or an antigen binding fragment thereof) that binds to an antigen (eg, CoVS) and inhibits or blocks the binding of another antigen binding protein (eg, an antibody or an antigen binding fragment thereof) to the antigen. The term also includes competition between two antigen binding proteins, for example antibodies in both orientations, i.e. a first antibody that binds and blocks the binding of a second antibody, and vice versa. In certain embodiments, the first antigen binding protein (eg, antibody) and the second antigen binding protein (eg, antibody) can bind to the same epitope. Alternatively, the first and second antigen-binding proteins (eg, antibodies) may bind to different but, eg, overlapping epitopes, with binding of one inhibiting or blocking binding of the second antibody, eg, through steric hindrance. Competition between antigen-binding proteins (eg, antibodies) can be measured by methods known in the art, for example, by real-time label-free biolayer interferometry. Epitope mapping (eg, by alanine scanning or hydrogen-deuterium exchange (HDX)) can be used to determine whether two or more antibodies are non-competitive (eg, on a spike protein receptor-binding domain (RBD) monomer) competing for the same and the same epitope or competing but characterized by different microepitopes (eg, identified by HDX). In an embodiment of the present invention, the competition between the first and second anti-CoV-S antigen-binding proteins (e.g., antibodies) is determined by measuring the ability of the immobilized first anti-CoV-S antigen-binding protein (e.g., antibody) (not initially complexed with the CoV-S protein) to bind with a soluble CoV-S protein complexed with a second antigen-binding protein against CoVS (for example, an antibody). The decrease in the ability of the first anti-CoV-S antigen-binding protein (e.g., antibody) to bind to the CoV-S protein in the complex compared to the CoV-S protein not included in the complex indicates that the first and second anti-CoV-S antigen-binding proteins are S (eg antibodies) compete. The degree of competition can be expressed as the percentage of binding attenuation. Such competition can be measured by real-time, label-free biolayer interferometry, such as the Octet RED384 biosensor (Pall ForteBio Corp.), ELISA (enzyme-linked immunosorbent assay), or SPR (surface plasmon assay).

- 13 044746 resonance).

Competition for binding between antigen-binding proteins against CoV-S (e.g., monoclonal antibodies (mAbs)) can be determined by label-free real-time biolayer interferometry on the Octet RED384 biosensor (Pall ForteBio Corp.). For example, to determine the competition between two anti-CoV-S monoclonal antibodies, anti-CoV-S mAb can first be captured on Octet biosensor tips coated with anti-hFc antibody (Pall ForteBio Corp., #185060) by immersing the tips in a solution of anti-CoV-S mAb ( hereinafter referred to as mAb1). As a positive control for blocking, antibody-captured biosensor tips can then be saturated with a known blocking isotype control mAb (hereinafter referred to as blocking mAb) by immersion in the blocking mAb solution. Then, to determine the presence or absence of mAb2 competition with mAb1, biosensor tips can be immersed in a solution of complexes of the CoV-S polypeptide and a second anti-CoV-S mAb (later referred to as mAb2), incubated for some time, and determine the binding of mAb1 to the CoV-S polypeptide. Biosensor tips can be washed with buffer between each experimental step. The real-time binding reaction can be monitored throughout the experiment, and the binding-based response can be recorded at the end of each step.

For example, in an embodiment of the present invention, the assay is performed at 25°C and a pH of approximately 7, eg 7.4, eg in the presence of a buffer, salt, surfactant and non-specific protein (eg bovine serum albumin).

Typically, an antibody or antigen binding fragment of the present invention, modified in any way, retains the ability to specifically bind to CoV-S, e.g., retains at least 10% binding activity against CoV-S (compared to the parent antibody) when expressed this activity is on a molar basis. Preferably, the antibody or antigen binding fragment of the present invention retains at least 20, 50, 70, 80, 90, 95 or 100% or more binding affinity for CoV-S compared to the parent antibody. It is further contemplated that the antibody or antigen binding fragment of the present invention may contain conservative or non-conservative amino acid substitutions (referred to as conservative variants or functionally conserved antibody variants) that do not substantially affect its biological activity.

A variant polypeptide, e.g., immunoglobulin chain (e.g., _VH , _VL , HC, or LC of mAb8021; VH, _VL , HC, or LC of mAb8028, or VH, _VL , HC, or LC of mAb8029) refers to a polypeptide containing an amino acid sequence at least about 70-99.9% (for example, 70, 72, 74, 75, 76, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.5, 99.9%) is identical or similar to the mentioned amino acid sequence presented herein (for example, SEQ ID NO: 2, 10, 18, 20 , 22, 30, 38, 40, 42, 50, 58 or 60); when performing a comparison using the BLAST algorithm, in which the parameters of the algorithm are selected by obtaining the maximum match between matching sequences over the entire length of the corresponding reference sequences (e.g., expected threshold: 10; word size: 3; maximum match in query range: 0; BLOSUM matrix 62; penalties for omissions: presence 11, extension 1; conditional adjustment of the matrix of compositional contributions).

A polynucleotide variant refers to a polynucleotide comprising at least about 70-99.9% of the nucleotide sequence (e.g., at least 70, 72, 74, 75, 76, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 99.5, 99.9%) identical to the referenced nucleotide sequence presented herein (e.g. , SEQ ID NO: 1, 9, 17, 19, 21, 29, 37, 39, 41, 49, 57 or 59); when performing a comparison using the BLAST algorithm, in which the parameters of the algorithm are selected by obtaining the maximum match between corresponding sequences over the entire length of the corresponding reference sequences (e.g., expected threshold: 10; word size: 28; maximum match in query range: 0; match score /inconsistencies: 1, -2; penalties for omission: linear).

Antigen-binding proteins against CoV-S, for example, antibodies and antigen-binding fragments of the present invention, in one embodiment of the present invention contain an immunoglobulin heavy chain variable region characterized by at least 70% (for example, 80, 85, 90, 91, 92 , 93, 94, 95, 96, 97, 98, 99% or greater) amino acid sequence identity to the HCVR amino acid sequences presented in table. 1; and/or an immunoglobulin light chain variable region having at least 70% (e.g., 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99% or greater) amino acid sequence identity to amino acid sequences LCVR presented in table. 1.

In addition, the antigen binding protein against CoV-S according to the present invention may comprise a polypeptide containing the amino acid sequence presented herein, excluding one or more (for example, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) mutations, for example, missense mutations (eg, conservative substitutions), nonsense mutations, deletions or insertions. For example, the present invention includes antigen binding proteins containing a light chain variant

- 14 044746 immunoglobulin containing the amino acid sequence LCVR presented in table. 1, but containing one or more of these mutations, and/or an immunoglobulin heavy chain variant containing the amino acid sequence HCVR presented in table. 1, but containing one or more of these mutations. In an embodiment of the present invention, the anti-CoV-S antigen binding protein comprises an immunoglobulin light chain variant comprising CDR-L1, CDR-L2, and CDRL3, wherein one or more (e.g., 1, 2, or 3) of such CDRs comprises one or more of such mutations (e.g., conservative substitutions), and/or an immunoglobulin heavy chain variant comprising CDR-H1, CDR-H2, and CDR-H3, wherein one or more (e.g., 1 or 2 or 3) of such CDRs contains one or more of such mutations (for example, conservative substitutions). Replacements may be in the CDR, framework region, or constant region.

In addition, the present invention provides variants of antigen binding proteins against CoV-S, for example, antibodies or antigen binding fragments thereof containing one or more of the CDR variants (for example, any one or more of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and/or CDR-H3) presented herein, having at least 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99 or 99.9% sequence identity or similarity to, for example, the heavy chain and light chain CDRs from Table. 1.

Embodiments of the present invention also include antibodies and antigen-binding fragments thereof against CoV-S containing immunoglobulin _VH and _VL ; or HC and LC containing an amino acid sequence having 70% or more (e.g., 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98%, or 99%) total amino acid sequence identity or similarity in with respect to the amino acid sequences of the corresponding VH, VL, HC or LC specifically presented herein, however, CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2 and CDRH3 of such immunoglobulins are not variants and contain the amino acid sequences CDRs presented in table. 1. Thus, in such embodiments, implementations of the CDRs in the antigen binding protein variants are not themselves variants.

Conservatively modified variant antibodies against CoV-S and their antigen binding fragments are also included in the scope of the present invention. The terms conservatively modified variant or conservative substitution refer to a variant containing one or more substitutions of amino acids in a polypeptide with other amino acids having similar characteristics (eg, charge, side chain size, hydrophobicity/hydrophilicity, conformation and backbone rigidity, etc.). Such changes can often be made without significantly interfering with the biological activity of the antibody or fragment. Those skilled in the art will appreciate that, in general, single amino acid substitutions in non-essential regions of a polypeptide do not significantly affect biological activity (see, for example, Watson et al. (1987) Molecular Biology of the Gene, The Benjamin/Cummings Pub . Co., p. 224 ( ^4th Ed.)). In addition, substitutions of structurally or functionally similar amino acids are less likely to result in significant impairment of biological activity.

Examples of groups of amino acids containing side chains with similar chemical properties include 1) aliphatic side chains: glycine, alanine, valine, leucine and isoleucine; 2) aliphatic hydroxyl side chains: serine and threonine; 3) amide-containing side chains: asparagine and glutamine; 4) aromatic side chains: phenylalanine, tyrosine and tryptophan; 5) main side chains: lysine, arginine and histidine; 6) acid side chains: aspartate and glutamate and 7) sulfur side chains: cysteine and methionine. Preferred groups of conservative amino acid substitutions are: valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, glutamate aspartate and asparagine-glutamine. Alternatively, a conservative replacement is any change that has a positive value in the PAM250 log-likelihood matrix described in the paper by Gonnet et al. (1992) Science 256:1443 45.

Functionally conserved variants of antibodies against CoV-S and their antigen-binding fragments are also included in the present invention. Any of the anti-CoV-S antibody variants and their antigen-binding fragments (discussed herein) may be functionally conserved variants. Such functionally conservative variants can in some cases also be characterized as conservatively modified variants. Functionally conserved variants, as used herein, refer to variants of anti-CoV-S antibodies or antigen-binding fragments thereof in which one or more amino acid residues are changed without significantly affecting one or more of the functional properties of the antibody or fragment. In an embodiment of the present invention, a functionally conserved variant of an anti-CoV-S antibody or antigen binding fragment thereof of the present invention comprises a variant amino acid sequence and exhibits one or more of the following functional properties:

inhibits the growth of coronaviruses (eg, SARS-CoV-2, SARS-CoV and/or MERS-CoV) in cells expressing ACE2 and/or TMPRSS2 (eg, Calu-3 cells);

does not bind significantly to MDCK/Tet-on cells not expressing ACE2

- 15 044746 and/or TMPRSS2;

limits the spread of coronavirus infection (eg, SARS-CoV-2, SARS-CoV and/or MERS-CoV) of cells, such as Calu-3, in vitro; and/or protects a recombinant mouse expressing human TMPRSS2 and/or ACE2 protein from death caused by a coronavirus infection (e.g., SARS-CoV-2, SARS-CoV, or MERS-CoV), for example, when the mouse is infected with an otherwise lethal dose virus, optionally in combination with a second therapeutic agent.

Protects a recombinant mouse expressing human TMPRSS2 and/or ACE2 protein from weight loss caused by coronavirus infection (e.g., SARS-CoV-2, SARS-CoV, or MERSCoV), such as when the mouse is infected with a dose of virus that would otherwise cause weight loss , optionally in combination with a second therapeutic agent.

A neutralizing or antagonistic antigen-binding protein against CoV-S, e.g., an antibody or antigen-binding fragment, refers to a molecule that inhibits the activity of CoV-S to any detectable extent, e.g., inhibiting the ability of CoV-S to bind to a receptor, e.g., ACE2, be cleaved by a protease, e.g. , TMPRSS2, or mediate viral entry into the host cell or viral replication in the host cell.

Table 1 refers to antigen binding proteins, for example, antibodies and antigen binding fragments thereof comprising a heavy chain or VH (or a variant thereof) and a light chain or VL (or a variant thereof) as set forth below; or containing a _VH containing their CDRs (CDR-H1 (or a variant thereof), CDR-H2 (or a variant thereof) and CDR-H3 (or a variant thereof)) and a VL containing their CDRs (CDR-L1 (or a variant thereof) ), CDRL2 (or a variant thereof) and CDR-L3 (or a variant thereof)), for example, wherein the immunoglobulin chains, variable regions and/or CDRs comprise the specific amino acid sequences described below.

Antibodies described herein also include embodiments in which the VH is attached to wild-type IgG4 (eg, where residue 108 is S) or variants of IgG4 (eg, where residue 108 is P).

Antibodies and antigen-binding fragments of the present invention contain immunoglobulin chains containing the amino acid sequences presented herein, as well as post-translational modifications of the antibody in cells and in vitro. For example, the present invention includes antibodies and antigen-binding fragments thereof that specifically bind to CoV-S containing the heavy and/or light chain amino acid sequences provided herein (e.g., CDR-H1, CDR-H2, CDR-H3, CDR-L1 , CDR-L2 and/or CDR-L3), as well as antibodies and fragments in which one or more amino acid residues are glycosylated, one or more Asn residues are deamidated, one or more residues (for example, Met, Trp and/or His) are oxidized , N-terminal Gln is pyroglutamate (pyroE) and/or C-terminal lysine is missing.

The amino acid and nucleotide sequences of typical antibodies against the SARS-CoV2-Spike protein (SARS-CoV-2-S) are shown in the table of typical sequences below.

Table of typical sequences.________________________________________

Antibody designation Component Subsequence SEQ ID NO mAT!0933 Amino acids HCVR QVQLVESGGGLVKPGGSLRLSCAASGFTFSD YYMSWIRQAPGKGLEWVSYITYSGSTIYYAD S VKGRFTISRDNAKS SLYLQMNSLRAEDT AV YYCARDRGTTMVPFDYWGQGTLVTVSS 202 HCDR1 GFTFSDYY 204 HCDR2 ITYSGTI 206 HCDR3 ARDRGTTTMVPFDY 208 LCVR DIQMTQSPSSLSASVGDRVTITCQASQDITNY LNW YQQKPGK APKLLIYAASNLETGVP SRF S GSGSGTDFTFTISGLQPEDIATYYCQQYDNLP LTFGGGTKVEIK 210 LCDR1 QDITNY 212 LCDR2 A.A.S. 55 LCDR3 QQYDNLPLT 214

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NS QVQLVESGGGLVKPGGSLRLSCAASGFTFSD YYMSWIRQAPGKGLEWVSYITYSGSTIYYAD S VKGRFTISRDNAKS SLYLQMNSLRAEDT AV YYCARDRGTTMVPFDYWGQGTLVTVSSAST KGPSVFPLAPSSKSTSGGTAALGCLVKDYFPE PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS VVTVPSSSLGT QTYICNVNHKPSNTKVDKKV EPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK DTLMISRTPEVTCVVVDVSHEDPEVKFNWYV DGVEVHNAKTKPREEQYNSTYRVVSVLTVL HQDWLNGKEYKCKVSNKALPAPIEKTISKAK GQPREPQVYTLPPSRDELTKNQVSLTCLVKGF YPSDI AVEWESNGQPENNYKTTPPVLDSDGSF FL YSKLT VDKSRWQQGNVF SC S VMHE A LHN HYTQKSLSLSPGK 216 L.C. DIQMTQSPSSLSASVGDRVTITCQASQDITNY LNWYQQKPGKAPKLLIYAASNLETGVPSRFS GSGSGTDFTFTISGLQPEDIATYYCQQYDNLP LTFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSG TASVVCLLNNFYPREAKVQWKVDNALQSGN SQESVTEQDSKDSTYSLSSTLTLSKADY EKHK VYACEVTHQGLSSPVTKSFNRGEC 218 Nucleic acids HCVR CAGGTGCAGCTGGTGGAGTCTGGGGGAGGC TTGGTCAAGCCTGGAGGGTCCCTGAGACTC TCCTGTGCAGCCTCTGGATTCACCTTCAGTG ACTACTACATGAGCTGGATCCGCCAGGCTC CAGGGAAGGGGCTGGAGTGGGTTTCATACA TTACTTATAGTGGTAGTACCATATACTACGC AGACTCTGTGAAGGGCCGATTCACCATCTC CAGGGACAACGCCAAGGCTC ACTGTATCT GCAAATGAACAGCCTGAGAGCCGAGGACA CGGCCGTGTATTACTGTGCGAGAGATCGCG GTACAACTATGGTCCCCTTTGACTACTGGG GCCAGGGAACCCTGGTCACCGTCTCCTCA 201

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HCDR1 GGATTCACCTTCAGTGACTACTAC 203 HCDR2 ATTACTTATAGTGGTAGTACCATA 205 HCDR3 GCGAGAGATCGCGGTACAACTATGGTCCCC TTTGACTAC 207 LCVR GACATCCAGATGACCCAGTCTCCATCCTCC CTGTCTGCATCTGTAGGAGACAGAGTCACC ATCACTTGCCAGGCGAGTCAGGACATTACC AACTATTTAAATTGGTATCAGCAGAAACCA GGGAAAGCCCCTAAGCTCCTGATCTACGCT GCATCCAATTTGGAAACAGGGGTCCCATCA AGGTTCAGTGGAAGTGGATCTGGGACAGAT TTTACTTTCACCATCAGCGGCCTGCAGC CTG AAGATATTGCAACATATTACTGTCAACAGT ATGATAATCTCCTCTCACTTTCGGCGGAG GGACCAAGGTGGAGATCAAA 209 LCDR1 CAGGACATTACCAACTAT 211 LCDR2 GCTGCATCC 54 LCDR3 CAACAGTATGATAATTCTCCCTCTCACT 213 HC CAGGTGCAGCTGGTGGAGTCTGGGGGAGGC TTGGTCAAGCCTGGAGGGTCCCTGAGACTC TCCTGTGCAGCCTCTGGATTCACCTTCAGTG ACTACTACATGAGCTGGATCCGCCAGGCTC CAGGGAAGGGGCTGGAGTGGGTTTCATACA TTACTTATAGTGGTAGTACCATATACTACGC AGACTCTGTGAAGGGCCGATTCACCATCTC CAGGGACAACGCCAAGGCTC ACTGTATCT GCAAATGAACAGCCTGAGAGCCGAGGACA CGGCCGTGTATTACTGTGCGAGAGATCGCG GTACAACTATGGTCCCCTTTGACTACTGGG GCCAGGGAACCCTGGTCACCGTCTCCTCAG CCTCCACCAAGGGCCCATCGGTCTTCCCCCT GGCACCCTCCTCCAAGAGCACCTCTGGGGG CACAGCGGCCCTGGGCTGCCTGGTCAAGGA CTACTTCCCCGAACC GGTGACGGTGTCGTG 215

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GAACTCAGGCGCCCTGACCAGCGGCGTGCA CACCTTCCCGGCTGTCCTACAGTCCTCAGG ACTCTACTCCCTCAGCAGCGTGGTGACCGT GCCCTCCAGCAGCTTGGGCACCCAGACCTA CATCTGCAACGTGAATCACAAGCCCAGCAA CACCAAGGTGGACAAGAAAGTTGAGCCCA AATCTTGTGACAAAACTCACACATGCCCAC CGTGCCCAGCACCTGAACTCCTGGGGG GAC CGTCAGTCTTCCTCTTCCCCCCAAAACCCAA GGACACCCTCATGATCTCCCGGACCCCTGA GGTCACATGCGTGGTGGTGGACGTGAGCCA CGAAGACCCTGAGGTCAAGTTCAACTGGTA CGTGGACGGCGTGGAGGTGCATAATGCCAA GACAAAGCCGCGGGAGGAGCAGTACAACA GCACGTACCGTGTGGTCAGCGTCCTCACCG TCCTGCACCAGGACT GGCTGAATGGCAAGG AGTACAAGTGCAAGGTCCAACAAAGCCC TCCCAGCCCCCATCGAGAAAACCATCTCC AAAGCCAAAGGGCAGCCCCGAGAACCACA GGTGTACACCCTGCCCCCATCCCGGGATGA GCTGACCAAGAACCAGGTCAGCCTGACCTG CCTGGTCAAAGGCTTCTATCCCAGCGACAT CGCCGTGGAGTGGGAGAGCAATGGGCAGC CGGAGAACAACTAC AATGA L.C. GACATCCAGATGACCCAGTCTCCATCCTCC CTGTCTGCATCTGTAGGAGACAGAGTCACC ATCACTTGCCAGGCGAGTCAGGACATTACC AACTATTTAAATTGGTATCAGCAGAAACCA GGGAAAGCCCCTAAGCTCCTGATCTACGCT 217

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GCATCCAATTTGGAAACAGGGGTCCCATCA AGGTTCAGTGGAAGTGGATCTGGGACAGAT TTTACTTTCACCATCAGCGGCCTGCAGCCTG AAGATATTGCAACATATTACTGTCAACAGT ATGATAATCTCCTCTCACTTTCGGCGGAG GGACCAAGGTGGAGATCAAACGAACTGTG GCTGCACCATCTGTCTTCATCTTCCCGCCAT CTGATGAGCAGTTGAAATCTGGAACTGC CT CTGTTGTGTGCCTGCTGAATAACTTCTATCC CAGAGAGGCCAAAGTACAGTGGAAGGTGG ATAACGCCCTCCAATCGGGTAACTCCCAGG AGAGTGTCACAGAGCAGGACAGCAAGGAC AGCACCTACAGCCTCAGCAGCACCCTGACG CTGAGCAAAGCAGACTACGAGAAACACAA AGTCTACGCCTGCGAAGTCACCCATCAGGG CCTGAGCTCGCCCGTCACAAAGA GCTTCAA CAGGGGAGAGTGTTAG mAT!0934 Amino acids HCVR EVQLVESGGGLVKPGGSLRLSCAASGITFSNA WMSWVRQAPGKGLEWVGRIKSKTDGGTTD YAAPVKGRFTISRDDSKNTLYLQMNSLKTED TAVYYCTTARWDWYFDLWGRGTLVTVSS 220 HCDR1 GITFSNAW 222 HCDR2 IKSKTDGGTT 224 HCDR3 TTARWDWYFDL 226 LCVR DIQMTQSPSSLSSASVGDRVTITCQASQDIWNY INWYQQKPGKAPKLLIYDASNLKTGVPSRFS GSGSGTDFTFTISSLQPEDIATYYCQQHDDLPP TFGQGTKVEIK 228 LCDR1 QDIWNY 230 LCDR2 DAS 194 LCDR3 QQHDDLPPT 232 NS EVQLVESGGGLVKPGGSLRLSCAASGITFSNA WMSWVRQAPGKGLEWVGRIKSKTDGGTTD 234

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YAAPVKGRFTISRDDSKNTLYLQMNSLKTED TAVYYCTTARWDWYFDLWGRGTLVTVSSAS TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTQTYICNVNHKPSNTKVDKK VEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKP KDTLMISRT PEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEAL HNHY TQKSLSLSPGK L.C. DIQMTQSPSSLSASVGDRVTITCQASQDIWNY INWYQQKPGKAPKLLIYDASNLKTGVPSRFS GSGSGTDFTFTISSLQPEDIATYYCQQHDDLPP TFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGT ASVVCLLNNFYPREAKVQWKVDNALQSGNS QESVTEQDSKDSTYSLSSTLTLSKADY EKHKV YACEVTHQGLSSPVTKSFNRGEC 236 Nucleic acids HCVR GAGGTGCAGCTGGTGGAGTCTGGGGGAGG CTTGGTAAAGCCTGGGGGGTCCCTTAGACT CTCCTGTGCAGCCTCTGGAATCACTTTCAGT AACGCCTGGATGAGTTGGGTCCGCCAGGCT CCAGGGAAGGGGCTGGAGTGGGTTGGCCGT ATTAAAAGCAAAACTGATGGTGGGACAAC AGACTACGCCGCACCCGTGAAAGGCAGATT CACCATCTCAAGAGATGATTC A 219 HCDR1 GGAATCACTTTCAGTAACGCCTGG 221

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HCDR2 ATTAAAAGCAAAACTGATGGTGGGACAAC A 223 HCDR3 ACCACAGCGAGGTGGGACTGGTACTTCGAT CTC 225 LCVR GACATCCAGATGACCCAGTCTCCATCCTCC CTGTCTGCATCTGTAGGAGACAGAGTCACC ATCACTTGCCAGGCGAGTCAGGACATTTGG AATTATAAAATTGGTATCAGCAGAAACCA GGGAAGGCCCCTAAGCTCCTGATCTACGAT GCATCCAATTTGAAAACAGGGGTCCCATCA AGGTTCAGTGGAAGTGGATCTGGGACAGAT TTTACTTTCACCATCAGCAGCCT GCAGCCTG AAGATATTGCAACATATTACTGTCAACAGC ATGATGATCTCCCTCCGACCTTCGGCCAAG GGACCAAGGTGGAAATCAAA 227 LCDR1 CAGGACATTTGGAATTAT 229 LCDR2 GATGCATCC 193 LCDR3 CAACAGCATGATGATCTCCCTCCGACC 231 NS GAGGTGCAGCTGGTGGAGTCTGGGGGAGG CTTGGTAAAGCCTGGGGGGTCCCTTAGACT CTCCTGTGCAGCCTCTGGAATCACTTTCAGT AACGCCTGGATGAGTTGGGTCCGCCAGGCT CCAGGGAAGGGGCTGGAGTGGGTTGGCCGT ATTAAAAGCAAAACTGATGGTGGGACAAC AGACTACGCCGCACCCGTGAAAGGCAGATT CACCATCTCAAGAGATGATTC AAAAAACAC GCTGTATCTACAAATGAACAGCCTGAAAAC CGAGGACACAGCCGTGTATTACTGTACCAC AGCGAGGTGGGACTGGTACTTCGATCTCTG GGGCCGTGGCACCCTGGTCACTGTCTCCTC AGCCTCCACCAAGGGCCCATCGGTCTTCCC CCTGGCACCCTCCTCCAAGAGCACCTCTGG GGGCACAGCGGCCCTGGGCTGCCTGGTCAA GGACTACTTCCCCGAA CCGGTGACGGTGTC GTGGAACTCAGGCGCCCTGACCAGCGGCGT 233

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GCACACCTTCCCGGCTGTCCTACAGTCCTCA GGACTCTACTCCCTCAGCAGCGTGGTGACC GTGCCCTCCAGCAGCTTGGGCACCCAGACC TACATCTGCAACGTGAATCACAAGCCCAGC AACACCAAGGTGGACAAGAAAGTTGAGCC CAAATCTTGTGACAAAACTCACACATGCCC ACCGTGCCCAGCACCTGAACTCCTGGGGGG ACCGTCAGTCTTCCTCTTCCCCAAAAC CC AAGGACACCCTCATGATCTCCCGGACCCCT GAGGTCACATGCGTGGTGGTGGACGTGAGC CACGAAGACCCTGAGGTCAAGTTCAACTGG TACGTGGACGGCGTGGAGGTGCATAATGCC AAGACAAAGCCGCGGGAGGAGCAGTACAA CAGCACGTACCGTGTGGTCAGCGTCCTCAC CGTCCTGCACCAGGACTGGCTGAATGGCAA GGAGTACAAGTGCAAGG TCTCCAACAAAGC CCTCCCAGCCCCCATCGAGAAAACCATCTC C AAAGCCAAAGGGCAGCCCCGAGAACCACA GGTGTACACCCTGCCCCCATCCCGGGATGA GCTGACCAAGAACCAGGTCAGCCTGACCTG CCTGGTCAAAGGCTTCTATCCCAGCGACAT CGCCGTGGAGTGGGAGAGCAATGGGCAGC CGGAGAACAACTACAAGACCACGCCTCCCG TGCTGGACTCCGACGGCTCCTTCTTCCTCTA CAGCAAGCTCACCGTGGACAAGAGCA GGT GGCAGCAGGGGAACGTCTTCTCATGCTCCG TGATGCATGAGGCTCTGCACAACCACTACA CGCAGAAGTCCCTCTCCCTGTCTCCGGGTA AATGA L.C. GACATCCAGATGACCCAGTCTCCATCCTCC CTGTCTGCATCTGTAGGAGACAGAGTCACC ATCACTTGCCAGGCGAGTCAGGACATTTGG AATTATAAAATTGGTATCAGCAGAAACCA GGGAAGGCCCCTAAGCTCCTGATCTACGAT 235

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GCATCCAATTTGAAAACAGGGGTCCCATCA AGGTTCAGTGGAAGTGGATCTGGGACAGAT TTTACTTTCACCATCAGCAGCCTGCAGCCTG AAGATATTGCAACATATTACTGTCAACAGC ATGATGATCTCCCTCCGACCTTCGGCCAAG GGACCAAGGTGGAAATCAAACGAACTGTG GCTGCACCATCTGTCTTCATCTTCCCGCCAT CTGATGAGCAGTTGAAATCTGGAACTGCCT CTGTTGTGTGCCTGCTGAATAACTTCTATCC CAGAGAGGCCAAAGTACAGTGGAAGGTGG ATAACGCCCTCCAATCGGGTAACTCCCAGG AGAGTGTCACAGAGCAGGACAGCAAGGAC AGCACCTACAGCCTCAGCAGCACCCTGACG CTGAGCAAAGCAGACTACGAGAAACACAA AGTCTACGGCCTGCGAAGTCACCCATCAGGG CCTGAGCTCGCCCGTCACAAAGAG CTTCAA CAGGGGAGAGTGTTAG mAT!0987 Amino acids HCVR QVQLVESGGGVVQPGRSLRLSC AASGFTF SN YAMYWVRQAPGKGLEWVAVISYDGSNKYY ADSVKGRFTISRDNSKNTLYLQMNSLRTEDT AVYYC ASGSD YGDYLLVYWGQGTLVT VS S 640 HCDR1 GFTFSNYA 642 HCDR2 ISYDGSNK 499 HCDR3 ASGSDYGDYLLVY 644 LCVR QSALTQPASVSGSPGQSITISCTGTSSDVGGYN YVSWYQQHPGKAPKLMIYDVSKRPSGVSNRF SGSKSGNTASLTISGLQSEDEADYYCNSLTSIS TWVFGGGTKLTVL 646 LCDR1 SSDVGGYNY 648 LCDR2 DVS 650 LCDR3 NSLTSISTWV 652 HC QVQLVESGGGVVQPGRSLRLSC AASGFTF SN YAMYWVRQAPGKGLEWVAVISYDGSNKYY 654

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ADSVKGRFTISRDNSKNTLYLQMNSLRTEDT AVYYC ASGSD YGDYLLVYWGQGTLVT VS SA STKGPSVFPLAPSSKSTSGGTAALGCLVKDYF PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL S S VVT VPS S SLGTQT YICNVNHKP SNTK VDKK VEPKSCDKTHTCPPCPAPELLGGPSVFL FPPKP KDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKA KGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNV FSCSVMHEAL HNHYTQKSLSLSPGK L.C. QSALTQPASVSGSPGQSITISCTGTSSDVGGYN YVSWYQQHPGKAPKLMIYDVSKRPSGVSNRF SGSKSGNTASLTISGLQSEDEADYYCNSLTSIS TWVFGGGTKLTVLGQPKAAPSVTLFPPSSEEL QANKATLVCLISDFYPGAVTVAWKADSSPVK AGVETTTPSKQ SNNK YAAS S YLSLTPEQW KS HRSYSCQVTHEGSTVEKTVAPTECS 656 Nucleic acids HCVR CAGGTGCAGCTGGTGGAGTCTGGGGGAGGC GTGGTCCAGCCTGGGAGGTCCCTGAGACTC TCCTGTGCAGCCTCTGGATTCACCTTCAGTA ACTATGCTATGTACTGGGTCCGCCAGGCTC CAGGCAAGGGGCTGGAGTGGGTGGCAGTT ATATCATATGATGGAAGTAATAAATACTAT GCAGACTCCGTGAAGGGCCGATTCACCATC TCCAGAGACAATTCCAAGAACACGCTG TAT CTGCAAATGAACAGCCTGAGAACTGAGGAC ACGGCTGTGTATTACTGTGCGAGTGGCTCC GACTACGGTGACTACTTATTGGTTTACTGG GGCCAGGGAACCCTGGTCACCGTCTCCTCA 639 HCDR1 GGATTCACCTTCAGTAACTATGCT 641 HCDR2 ATATCATATGATGGAAGTAATAAA 498

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HCDR3 GCGAGTGGCTCCGACTACGGTGACTACTTA TTGGTTTAC 643 LCVR CAGTCTGCCCTGACTCAGCCTGCCTCCGTGT CTGGGTCTCCTGGACAGTCGATCACCATCT CCTGCACTGGAACCAGCAGTGACGTTGGTG GTTATAACTATGTCTCCTGGTACCAACAAC ACCCAGGCAAAGCCCCCAAACTCATGATTT ATGATGTCAGTAAGCGGCCCTCAGGGGTTT CTAATCGCTTCTCTGGCTCCAAGTCTGGCAA CACGGCCTCCCTGACCATCTCTGGGC TCCA GTCTGAGGACGAGGCTGATTATTACTGCAA CTCTTTGACAAGCATCAGCACTTGGGTGTTC GGCGGAGGGACCAAGCTGACCGTCCTA 645 LCDR1 AGCAGTGACGTTGGTGGTTATAACTAT 647 LCDR2 GATGTCAGT 649 LCDR3 AACTCTTTGACAAGCATCAGCACTTGGGTG 651 NS CAGGTGCAGCTGGTGGAGTCTGGGGGAGGC GTGGTCCAGCCTGGGAGGTCCCTGAGACTC TCCTGTGCAGCCTCTGGATTCACCTTCAGTA ACTATGCTATGTACTGGGTCCGCCAGGCTC CAGGCAAGGGGCTGGAGTGGGTGGCAGTT ATATCATATGATGGAAGTAATAAATACTAT GCAGACTCCGTGAAGGGCCGATTCACCATC TCCAGAGACAATTCCAAGAACACGCTG TAT CTGCAAATGAACAGCCTGAGAACTGAGGAC ACGGCTGTGTATTACTGTGCGAGTGGCTCC GACTACGGTGACTACTTATTGGTTTACTGG GGCCAGGGAACCCTGGTCACCGTCTCCTCA GCCTCCACCAAGGGCCCATCGGTCTTCCCC CTGGCACCCTCCTCCAAGAGCACCTCTGGG GGCACAGCGGCCCTGGGCTGCCTGGTCAAG GACTACTTCCCCGAACCGGTGACGG TGTCG TGGAACTCAGGCGCCCTGACCAGCGGCGTG CACACCTTCCCGGCTGTCCTACAGTCCTCAG GACTCTACTCCCTCAGCAGCGTGGTGACCG 653

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TGCCCTCCAGCAGCTTGGGCACCCAGACCT ACATCTGCAACGTGAATCACAAGCCCAGCA ACACCAAGGTGGACAAGAAAGTTGAGCCC AAATCTTGTGACAAAACTCACACATGCCCA CCGTGCCCAGCACCTGAACTCCTGGGGGGA CCGTCAGTCTTCCTCTTCCCCCCAAAACCCA AGGACACCCTCATGATCTCCCGGACCCCTG AGGTCACATGCGTGGTGGTGGACG TGAGCC ACGAAGACCCTGAGGTCAAGTTCAACTGGT ACGTGGACGGCGTGGAGGTGCATAATGCCA AGACAAAGCCGCGGGAGGAGCAGTACAAC AGCACGTACCGTGTGGTCAGCGTCCTCACC GTCCTGCACCAGGACTGGCTGAATGGCAAG GAGTACAAGTGCAAGGTCTCCAACAAAGCC CTCCCAGCCCCCATCGAGAAAACCATCTCC AAAGCCAAAGGGCAGCCCCGA GAACCACA GGTGTACACCCTGCCCCCATCCCGGGATGA GCTGACCAAGAACCAGGTCAGCCTGACCTG CCTGGTCAAAGGCTTCTATCCCAGCGACAT CGCCGTGGAGTGGGAGAGCAATGGGCAGC CGGAGAACAACTACAAGACCACGCCTCCCG TGCTGGACTCCGACGGCTCCTTCTTCCTCTA CAGCAAGCTCACCGTGGACAAGAGCAGGT GGCAGCAGGGGAACGTCTT CTCATGCTCCG TGATGCATGAGGCTCTGCACAACCACTACA CGCAGAAGTCCCTCTCCCTGTCTCCGGGTA AATGA L.C. CAGTCTGCCCTGACTCAGCCTGCCTCCGTGT CTGGGTCTCCTGGACAGTCGATCACCATCT CCTGCACTGGAACCAGCAGTGACGTTGGTG GTTATAACTATGTCTCCTGGTACCAACAAC ACCCAGGCAAAGCCCCCAAACTCATGATTT ATGATGTCAGTAAGCGGCCCTCAGGGGTTT CTAATCGCTTCTCTGGCTCCAAGTCTGGCAA CACGGCCTCCCTGACCATCTCTGGGC TCCA 655

- 27 044746

GTCTGAGGACGAGGCTGATTATTACTGCAA CTCTTTGACAAGCATCAGCACTTGGGTGTTC GGCGGAGGGACCAAGCTGACCGTCCTAGGC CAGCCCAAGGCCGCCCCCTCCGTGACCCTG TTCCCCCCCTCCTCCGAGGAGCTGCAGGCC AACAAGGCCACCCTGGTGTGCCTGATCTCC GACTTCTACCCCGGCGCCGTGACCGTGGCC TGGAAGGCCGACTCCTCCCCCG TGAAGGCC GGCGTGGAGACCACCACCCCCTCCAAGCAG TCCAACAACAAGTACGCCGCCTCCTCCTAC CTGTCCCTGACCCCCGAGCAGTGGAAGTCC CACCGGTCCTACTCCTGCCAGGTGACCCAC GAGGGCTCCACCGTGGAGAAGACCGTGGCC CCCACCGAGTGCTCCTGA mAT!0989 Amino acids HCVR QVQLVQSGAEVKKPGASVKVSCKASGYIFTG YYMHWVRQAPGQGLEWMGWINPNSGGANY AQKFQGRVTLTRDTSITTVYMELSRLRFDDT AVYYCARGSRYDWNQNNWFDPWGQGTLVT VSS 678 HCDR1 GYIFTGYY 680 HCDR2 INPNSGGA 682 HCDR3 ARGSRYDWNQNNWFDP 684 LCVR QSALTQPASVSGSPGQSITISCTGTSSDVGTYN YVSWYQQHPGKAPKLMIFDVSNRPSGVSDRF SGSKSGNTASLTISGLQAEDEADYYCSSFTTSS TVVFGGGTKLTVL 686 LCDR1 SSDVGTYNY 688 LCDR2 DVS 650 LCDR3 SSFTTSSTVV 690 NS QVQLVQSGAEVKKPGASVKVSCKASGYIFTG YYMHWVRQAPGQGLEWMGWINPNSGGANY AQKFQGRVTLTRDTSITTVYMELSRLRFDDT AVYYCARGSRYDWNQNNWFDPWGQGTLVT 692

- 28 044746

VSSASTKGPSVFPLAPSSKSTSGGTAALGCLV KDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVV SV LTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSRDELTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM HEALHNHYTQKSLSLSPGK L.C. QSALTQPASVSGSPGQSITISCTGTSSDVGTYN YVSWYQQHPGKAPKLMIFDVSNRPSGVSDRF SGSKSGNTASLTISGLQAEDEADYYCSSFTTSS TVVFGGGTKLTVLGQPKAAPSVTLFPPSSEEL QANKATLVCLISDFYPGAVTVAWKADSSPVK AGVETTTPSKQ SNNK YAAS S YLSLTPEQWKS HR SYSCQVTHEGSTVEKTVAPTECS 694 Nucleic acids HCVR CAGGTGCAGCTGGTGCAGTCTGGGGCTGAG GTGAAGAAGCCTGGGGCCTCAGTGAAGGTC TCCTGCAAGGCTTCTGGATACATCTTCACCG GCTACTATATGCACTGGGTGCGACAGGCCC CTGGACAGGGGCTTGAGTGGATGGGATGGA TCAACCCTAACAGTGGTGGCGCAAACTATG CACAGAAGTTTCAGGGCAGGGTCACCCCTGA CCAGGGACACGTCCATCACCACAGTC TACA TGGAACTGAGCAGGCTGAGATTTGACGACA CGGCCGTGTATTACTGTGCGAGAGGATCCC GGTATGACTGGAACCAGAACAACTGGTTCG ACCCCTGGGGCCAGGGAACCCTGGTCACCG TCTCCTCA 677 HCDR1 GGATACATCTTCACCGGCTACTAT 679 HCDR2 ATCAACCCTAACAGTGGTGGCGCA 681 HCDR3 GCGAGAGGATCCCGGTATGACTGGAACCAG 683

- 29 044746

AACAACTGGTTCGACCCC LCVR CAGTCTGCCCTGACTCAGCCTGCCTCCGTGT CTGGGTCTCCTGGACAGTCGATCACCATCT CCTGCACTGGAACCAGCAGTGACGTTGGTA CTTATAACTATGTCTCCTGGTACCAACAAC ACCCAGGCAAAGCCCCCAAACTCATGATTT TTGATGTCAGTAATCGGCCCTCAGGGGTTT CTGATCGCTTCTCTGGCTCCAAGTCTGGCAA CACGGCCTCCCTGACCATCTCTGG GCTCCA GGCTGAGGACGAGGCTGATTATTACTGCAG CTCATTTACAACCAGCAGCACTGTGGTTTTC GGCGGAGGGACCAAGCTGACCGTCCTA 685 LCDR1 AGCAGTGACGTTGGTACTTATAACTAT 687 LCDR2 GATGTCAGT 649 LCDR3 AGCTCATTTACAACCAGCAGCACTGTGGTT 689 NS CAGGTGCAGCTGGTGCAGTCTGGGGCTGAG GTGAAGAAGCCTGGGGCCTCAGTGAAGGTC TCCTGCAAGGCTTCTGGATACATCTTCACCG GCTACTATATGCACTGGGTGCGACAGGCCC CTGGACAGGGGCTTGAGTGGATGGGATGGA TCAACCCTAACAGTGGTGGCGCAAACTATG CACAGAAGTTTCAGGGCAGGGTCACCCCTGA CCAGGGACACGTCCATCACCACAGTC TACA TGGAACTGAGCAGGCTGAGATTTGACGACA CGGCCGTGTATTACTGTGCGAGAGGATCCC GGTATGACTGGAACCAGAACAACTGGTTCG ACCCCTGGGGCCAGGGAACCCTGGTCACCG TCTCCTCAGCCTCCACCAAGGGCCCATCGG TCTTCCCCCTGGCACCCTCCTCCAAGAGCAC CTCTGGGGGCACAGCGGCCCTGGGCTGCCT GGTCAAGGACTACTTCCCCGAA CCGGTGAC GGTGTCGTGGAACTCAGGCGCCCTGACCAG CGGCGTGCACACCTTCCCGGCTGTCCTACA GTCCTCAGGACTCTACTCCCTCAGCAGCGT GGTGACCGTGCCCTCCAGCAGCTTGGGCAC 691

- 30 044746

CCAGACCTACATCTGCAACGTGAATCACAA GCCCAGCAACACCAAGGTGGACAAGAAAG TTGAGCCCAAATCTTGTGACAAAACTCACA CATGCCCACCGTGCCCAGCACCTGAACTCC TGGGGGGACCGTCAGTCTTCCTCTTCCCCCC AAAACCCAAGGACACCCTCATGATCTCCCG GACCCCTGAGGTCACATGCGTGGTGGTGGA CGTGAGCCACGAAGACCCTGAGGTC AAGTT CAACTGGTACGTGGACGGCGTGGAGGTGCA TAATGCCAAGACAAAGCCGCGGGAGGAGC AGTACAACAGCACGTACCGTGTGGTCAGCG TCCTCACCGTCCTGCACCAGGACTGGCTGA ATGGCAAGGAGTACAAGTGCAAGGTCTCCA ACAAAGCCCTCCCAGCCCCCATCGAGAAA ACCATCTCCAAAGCCAAAGGGCAGCCCCGA GAACCACAGGTGTACACCCTGCCCCCAT CC CGGGATGAGCTGACCAAGAACCAGGTCAG CCTGACCTGCCTGGTCAAAGGCTTCTATCCC AGCGACATCGCCGTGGAGTGGGAGAGCAA TGGGCAGCCGGAGAACAACTACAAGACCA CGCCTCCCGTGCTGGACTCCGACGGCTCCTT CTTCCTCTACAGCAAGCTCACCGTGGACAA GAGCAGGTGGCAGCAGGGGAACGTCTTCTC ATGCTCCGTGATGCATGAGGCTCTGC ACAA CCACTACACGCAGAAGTCCCTCTCCCTGTCT CCGGGTAAATGA L.C. CAGTCTGCCCTGACTCAGCCTGCCTCCGTGT CTGGGTCTCCTGGACAGTCGATCACCATCT CCTGCACTGGAACCAGCAGTGACGTTGGTA CTTATAACTATGTCTCCTGGTACCAACAAC ACCCAGGCAAAGCCCCCAAACTCATGATTT TTGATGTCAGTAATCGGCCCTCAGGGGTTT CTGATCGCTTCTCTGGCTCCAAGTCTGGCAA CACGGCCTCCCTGACCATCTCTGG GCTCCA GGCTGAGGACGAGGCTGATTATTACTGCAG 693 CTCATTTACAACCAGCAGCACTGTGGTTTTC GGCGGAGGGACCAAGCTGACCGTCCTAGGC CAGCCCAAGGCCGCCCCCTCCGTGACCCTG TTCCCCCCCTCCTCCGAGGAGCTGCAGGCC AACAAGGCCACCCTGGTGTGCCTGATCTCC GACTTCTACCCCGGCGCCGTGACCGTGGCC TGGAAGGCCGACTCCTCCCCCGTGAAGGCC GGCGTGGAGACCACCACC CCCTCCAAGCAG TCCAACAACAAGTACGCCGCCTCCTCCTAC CTGTCCCTGACCCCCGAGCAGTGGAAGTCC CACCGGTCCTACTCCTGCCAGGTGACCCAC GAGGGCTCCACGTGGAGAAGACCGTGGCC CCCACCGAGTGCTCCTGA

- 31 044746

Introduction of antibodies.

The present invention provides methods for administering an anti-CoVS antigen binding protein according to the present invention, for example, the protein presented in table. 1, comprising introducing an antigen binding protein into a subject (eg, a human). For example, the method includes puncturing the subject's body with a syringe needle and injecting an antigen binding protein into the subject's body, for example, into a vein, artery, tumor, muscle tissue or subcutaneous tissue of the subject.

The present invention provides a vessel (for example, a plastic or glass bottle, for example with a cap, or a chromatography column, a hollow needle or a syringe barrel) containing an anti-CoV-S antigen binding protein according to the present invention, for example, shown in table. 1.

The present invention also relates to an injection device containing one or more of the antigen binding proteins (eg, antibody or antigen binding fragment) that specifically bind to CoV-S, for example, those presented in table. 1, or a pharmaceutical composition thereof. The injection device can be packaged in a kit. An injection device is a device that introduces a substance into the body of a subject through a parenteral route, such as intramuscularly, subcutaneously, or intravenously. For example, the injection device may be a syringe (e.g., pre-filled with a pharmaceutical composition, e.g., an auto-injector), e.g., including a barrel or hollow compartment for holding an injected liquid (e.g., containing an antibody or fragment thereof, or a pharmaceutical composition thereof), a needle for puncturing the skin and/or blood vessels to inject fluid; and a piston for pushing liquid out of the cylinder through the needle hole. In an embodiment of the present invention, the injection device containing an antigen binding protein, for example, an antibody or an antigen binding fragment thereof from a combination according to the present invention, or a pharmaceutical composition thereof, is an intravenous (IV) injection device. Such a device may contain the antigen-binding protein or a pharmaceutical composition thereof in a cannula or trocar/needle, which may be attached to a tube, which may be attached to a bag or reservoir for containing fluid (eg, saline) introduced into the subject's body through the cannula or trocar /igloo. The antibody or fragment thereof, or a pharmaceutical composition thereof, in an embodiment of the present invention, can be administered to the device after insertion of the trocar and cannula into a vein of the subject and removal of the trocar from the inserted cannula. The IV device can, for example, be inserted into a peripheral vein (eg, a hand or arm); superior vena cava or inferior vena cava or into the right atrium of the heart (eg, central IV device); or into the subclavian, internal jugular or femoral vein and, for example, advance towards the heart until it reaches the superior vena cava or right atrium (eg central venous line). In an embodiment of the present invention, the injection device is an automatic injector; jet injector or external infusion pump. A jet injector uses a narrow, high-pressure jet of liquid to penetrate the epidermis, introducing an antibody or fragment thereof or a pharmaceutical composition thereof into the subject's body. External infusion pumps are medical devices that deliver an antibody or fragment thereof, or a pharmaceutical composition thereof, into the body of a subject in controlled quantities. External infusion pumps can be electrically or mechanically driven. Different pumps work differently, for example, a syringe pump holds liquid in a syringe reservoir and a movable piston controls the flow of liquid, an elastomeric pump holds liquid in an expandable balloon reservoir, and the pressure created by the elastic walls of the balloon controls the delivery of liquid. In a peristaltic pump, a set of rollers clamps onto a flexible tube, pushing fluid forward. A multi-channel pump can supply fluids from multiple reservoirs at different rates.

Obtaining human antibodies.

Methods for producing human antibodies in transgenic mice are known in the art. Any such known methods can be used in the context of the present invention to obtain human antibodies that specifically bind to CoV-S. To obtain antibodies to CoV-S, an immunogen containing any of the following compounds can be used. In certain embodiments of the present invention, antibodies of the present invention are obtained from mice immunized with full-length native CoV-S or live attenuated or inactivated virus, or DNA encoding a protein or fragment thereof. Alternatively, the CoV-S protein or fragment thereof can be produced using standard biochemical techniques, modified and used as an immunogen. In one embodiment of the present invention, the immunogen is a recombinantly produced CoV-S protein or a fragment thereof. In certain embodiments of the present invention, the immunogen may be a polypeptide vaccine against CoV-S. In certain embodiments, one or more secondary injections may be administered. In certain embodiments, the immunogen may be a recombinant CoV-S polypeptide expressed in E. coli or any other eukaryotic cells or

- 32 044746 mammalian cells, for example Chinese hamster ovary (CHO) cells.

When using VELOCIMMUNE® technology (see, for example, US Patent No. 6596541, Regeneron Pharmaceuticals, VELOCIMMUNE®) or any other known method for producing monoclonal antibodies, it is possible to first isolate chimeric antibodies with high affinity to CoV-S containing a human variable region and a constant region mouse area. VELOCIMMUNE® technology involves the creation of a transgenic mouse whose genome contains human heavy and light chain variable regions operably linked to endogenous mouse constant region loci such that the mouse produces an antibody containing the human variable region and the mouse constant region in response to antigenic stimulation. DNA encoding the variable regions of the heavy and light chains of the antibody is isolated and operably linked to DNA encoding the human heavy and light chain constant regions. The DNA is then expressed in a cell capable of expressing a fully human antibody.

Typically, a VELOCIMMUNE® mouse is exposed to the antigen in question, and lymphatic cells (eg, B cells) are recovered from the antibody-expressing mice. Lymphatic cells can be fused with myeloma cell lines to produce immortalized hybridoma cell lines, and such hybridoma cell lines are screened and selected to identify hybridoma cell lines that produce antibodies specific for the antigen in question. DNA encoding the heavy chain and light chain variable regions can be isolated and linked to the desired isotype heavy chain and light chain constant regions. Such an antibody protein can be produced in a cell, for example a CHO cell. Alternatively, DNA encoding the antigen-specific chimeric antibody or light and heavy chain variable domains can be isolated directly from antigen-specific lymphocytes.

Initially, high-affinity chimeric antibodies containing a human variable region and a mouse constant region are isolated. As in the experimental section below, antibodies are screened and selected for desired characteristics, including affinity, selectivity, epitope, etc. The mouse constant regions are replaced with the desired human constant region, resulting in a fully human antibody of the invention, e.g., IgG1 or Wild type IgG4 or modified IgG1 or IgG4. While the selected constant region may vary depending on the particular application, the characteristics of antigen binding with high affinity and target specificity are found in the variable region.

Antibodies against the coronavirus spike protein, including Fc variants.

In accordance with some embodiments of the present invention, antigen-binding proteins against CoV-S are provided, for example, antibodies or antigen-binding fragments thereof containing an Fc domain containing one or more mutations, for example, increasing or decreasing the binding of the antibody to the FcRn receptor, for example, at acidic pH compared to neutral pH. For example, the invention includes anti-CoV-S antibodies containing a mutation in the C _H 2 or C _H 3 region of the Fc domain, wherein said mutation(s) increase the affinity of the Fc domain for FcRn in an acidic environment (eg , in the endosome, where the pH ranges from about 5.5 to about 6.0). Such mutations may result in an increase in the serum half-life of the antibody when administered to an animal. Non-limiting examples of such Fc modifications include, for example, modification at position 250 (eg, E or Q); 250 and 428 (for example, L or F); 252 (eg L/Y/F/W or T), 254 (eg S or T) and 256 (eg S/R/Q/E/D or T); or modification to position 428 and/or 433 (for example, H/L/R/S/P/Q or K) and/or 434 (for example, A, W, H, F or Y [N434A, N434W, N434H, N434F or N434Y]); or modification according to provision 250 and/or 428; or modification at position 307 or 308 (eg, 308F, V308F) and 434. In one embodiment, the modification includes modification 428L (eg, M428L) and 434S (eg, N434S); modification 428L, 259I (for example, V259I) and 308F (for example, V308F); modification 433K (for example, H433K) and 434 (for example, 434Y); modification of 252, 254 and 256 (for example, 252Y, 254T and 256E); modification 250Q and 428L (for example, T250Q and M428L); and modification 307 and/or 308 (for example, 308F or 308P). In yet another embodiment, the modification includes modification 265A (eg, D265A) and/or modification 297A (eg, N297A).

For example, the present invention includes antigen binding proteins against CoV-S, for example, antibodies or antigen binding fragments containing an Fc domain containing one or more pairs or groups of mutations selected from the group consisting of: 250Q and 248L (for example, T250Q and M248L) ; 252Y, 254T and 256E (for example, M252Y, S254T and T256E); 428L and 434S (for example, M428L and N434S); 257I and 311I (for example, P257I and Q311I); 257I and 434H (for example, P257I and N434H); 376B and 434H (for example, D376V and N434H); 307A, 380A and 434A (eg T307A, E380A and N434A); and 433K and 434F (for example, H433K and N434F).

Antigen-binding proteins against CoV-S, for example, antibodies and antigen-binding fragments thereof containing _VH and/or VL provided herein, containing any possible combinations of the above Fc domain mutations, are contemplated within the scope of the present invention

- 33 044746 nia.

The present invention also includes anti-CoV-S antigen binding proteins, antibodies or antigen binding fragments comprising a VH as provided herein and a chimeric heavy chain constant region (CH), wherein the chimeric CH region contains segments derived from the CH regions of more than one immunoglobulin isotype. For example, antibodies of the present invention may comprise a chimeric CH region comprising all or part of a C _H 2 domain derived from a human IgG1, human IgG2 or human IgG4 molecule, in combination with all or part of a CH 3 domain derived from a human IgG1 molecule, Human IgG2 or human IgG4. In accordance with certain embodiments, the antibodies of the present invention comprise a chimeric CH region comprising a chimeric hinge region. For example, a chimeric hinge may comprise an upper hinge amino acid sequence (amino acid residues at positions 216 to 227 according to EC numbering) derived from the loop region of human IgG1, human IgG2, or human IgG4, in combination with a lower hinge sequence (amino acid residues at positions 228- 236 according to EC numbering) derived from the hinge region of human IgG1, human IgG2 or human IgG4. In certain embodiments, the chimeric hinge region comprises amino acid residues derived from a human IgG1 or human IgG4 upper hinge and amino acid residues derived from a human IgG2 lower hinge. An antibody comprising a chimeric CH region described herein may, in some embodiments, exhibit modified Fc effector functions without undesirably affecting the therapeutic or pharmacokinetic properties of the antibody. (See for example WO2014/022540).

Immunoconjugates.

The present invention covers antigen-binding proteins against CoV-S, for example, antibodies or antigen-binding fragments conjugated to another fragment, for example, a therapeutic fragment (immunoconjugate), for example, a toxoid or an antiviral drug for the treatment of influenza virus infection. In one embodiment of the present invention, an anti-CoV-S antibody or fragment thereof is conjugated to any of the additional therapeutic agents provided herein. As used herein, the term immunoconjugate refers to an antigen-binding protein, such as an antibody or antigen-binding fragment, chemically or biologically linked to a radioactive agent, cytokine, interferon, target or reporter fragment, enzyme, toxin, peptide or protein, or therapeutic agent. An antigen binding protein can be bound to a radioactive agent, cytokine, interferon, target or reporter fragment, enzyme, toxin or therapeutic agent at any position along the molecule as long as it is capable of binding its target (CoV-S). Examples of immunoconjugates include antibody-drug conjugates and antibody-toxin fusion proteins. In one embodiment of the present invention, the agent may be a second, different antibody that specifically binds to CoV-S. The type of therapeutic moiety that can be conjugated to an anti-CoV-S antigen-binding protein (e.g., antibody or fragments) should take into account the condition being treated and the desired therapeutic effect to be achieved. See, for example, Arnon et al., Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy, Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., Antibodies For Drug Delivery, Controlled Drug Delivery (2 ^nd Ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review, Monoclonal Antibodies 1984: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy, Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985), and Thorpe et al., The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates, Immunol. Rev., 62: 119-58 (1982).

Multispecific antibodies.

The present invention includes antigen binding proteins against CoV-S, for example, antibodies and antigen binding fragments thereof, as well as methods of using them and methods for creating such antigen binding proteins. The term antigen-binding proteins against CoV-S, e.g., antibodies or antigen-binding fragments, includes multispecific (e.g., bispecific or biparatopic) molecules containing at least one first antigen-binding domain that specifically binds to CoV-S (e.g., the antigen-binding domain of the antibody from Table 1). 1) and at least one second antigen binding domain that binds to another CoV-S antigen or epitope that is different from the epitope of the first antigen binding domain. In some embodiments, both the first antigen binding domain and the second antigen binding domain are selected from the antigen binding domains presented in Table. 1. In an embodiment of the present invention, the first and second epitopes overlap. In another embodiment of the present invention, the first and second epitopes do not overlap. For example, in an embodiment of the present invention, the multispecific antibody is a bispecific IgG antibody (e.g., IgG1 or IgG4) containing

- 34 044746 pressing the first antigen-binding domain that specifically binds to CoV-S, containing the heavy and light immunoglobulin chain of the antibody from the table. 1, and a second antigen-binding domain that specifically binds to another CoV-S epitope. In some embodiments, the bispecific IgG antibody (e.g., IgG1 or IgG4) comprises a first antigen binding domain that specifically binds to CoV-S and a second binding domain that binds to a host cell protein, such as ACE2 or TMPRSS2.

Antibodies from the table. 1 include multispecific molecules, for example, antibodies or antigen-binding fragments containing CDR-H and CDR-L, V _H and V _L , or HC and LC of these antibodies, respectively (including variants thereof presented herein).

In an embodiment of the present invention, the antigen binding domain that specifically binds to CoV-S, which can be included in a multispecific molecule, comprises:

a heavy chain variable domain sequence containing the amino acid sequences CDR-H1, CDR-H2 and CDR-H3 presented in table. 1, and (ii) a light chain variable domain sequence comprising the amino acid sequences CDR-L1, CDR-L2 and CDR-L3 presented in table. 1; or (2) (i) a heavy chain variable domain sequence comprising the amino acid sequence shown in Table. 1, and (ii) a light chain variable domain sequence containing the amino acid sequence shown in table. 1; or (3) (i) an immunoglobulin heavy chain sequence containing the amino acid sequence shown in table. 1, and (ii) an immunoglobulin light chain sequence containing the amino acid sequence shown in table. 1.

In an embodiment of the present invention, the multispecific antibody or fragment comprises more than two different binding specificities (e.g., is a trispecific molecule), e.g., one or more additional antigen binding domains that are the same as or different from the first and/or second antigen binding domains. them.

In one embodiment of the present invention, the bispecific antigen binding fragment comprises a first scFv (e.g., comprising the VH and _VL sequences of Table 1) having binding specificity for a first epitope (e.g., CoV-S) and a second scFv having binding specificity in relation to a second, different epitope. For example, in an embodiment of the present invention, the first and second scFv are linked to a linker, e.g., a peptide linker (e.g., a GS linker, e.g., (GGGGS) _n (SEQ ID NO: 834), where n is, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10). Other bispecific antigen binding fragments include the F(ab) ₂ bispecific IgG antibody containing the heavy and light chain CDRs from Table 1. 1, and another antibody that binds to a different epitope.

Methods of treatment.

The present invention provides methods for treating or preventing a viral infection (eg, coronavirus infection) by administering a therapeutically effective amount of an anti-CoV-S antigen binding protein, such as an antibody or antigen binding fragment (eg, from Table 1) to a subject (eg, a human) in need in such treatment or prevention.

Coronavirus infection can be treated or prevented in a subject by administering to the subject an anti-CoV-S antigen binding protein according to the present invention.

An effective or therapeutically effective dose of an anti-CoV-S antigen-binding protein, such as an antibody or antigen-binding fragment (e.g., from Table 1) for the treatment or prevention of a viral infection refers to an amount of the antibody or fragment sufficient to relieve one or more signs and/or symptoms infection in a subject being treated, either by inducing regression or elimination of such signs and/or symptoms or by suppressing the progression of such signs and/or symptoms. The dosage size depends on the age and size of the subject to whom the protein will be administered, the disease being treated, the pathological conditions, the route of administration, and the like. In an embodiment of the present invention, an effective or therapeutically effective dose of an antibody or antigen binding fragment thereof of the present invention for treating or preventing a viral infection, for example, in an adult human subject is from about 0.01 mg/kg to about 200 mg/kg, for example, up to approximately 150 mg/kg. In an embodiment of the present invention, the dosage is up to about 10.8 or 11 grams (eg, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 grams). Depending on the severity of the infection, the frequency and duration of treatment may be adjusted. In certain embodiments, the antigen binding protein of the present invention may be administered in an initial dose followed by one or more secondary doses. In certain embodiments, the initial dose may be followed by administration of a second or multiple subsequent doses of an antibody or antigen-binding fragment thereof in an amount that may be approximately the same as or less than the amount of the initial dose, with the time interval between subsequent doses being at least at least 1-3 days; at least one week, at least 2 weeks; at least 3 weeks; at least 4 weeks; at least 5 weeks; at least 6 weeks; at least 7 weeks; at least 8 weeks; at least 9 weeks; at least 10 weeks; at least 12 weeks; or at least 14 weeks.

As used herein, the term subject refers to a mammal (eg, rat, mouse, cat, dog, cow, sheep, horse, goat, rabbit), preferably a human, for example, in need of prevention and/or treatment of such a viral infection or cancer. The subject may have a viral infection, such as influenza infection, or may be predisposed to developing an infection. Subjects predisposed to developing infection, or subjects who may be at increased risk of contracting an infection (eg, coronavirus or influenza virus), include subjects with a weakened immune system due to an autoimmune disease, subjects receiving immunosuppressive therapy (eg, after an organ transplant) , subjects suffering from human immunodeficiency syndrome (HIV) or acquired immunodeficiency syndrome (AIDS), subjects with forms of anemia resulting in the depletion or destruction of white blood cells, subjects receiving radiation therapy or chemotherapy, or subjects suffering from an inflammatory disease. In addition, people who are very young (eg, 5 years of age or younger) or older (eg, 65 years of age or older) are at increased risk. Moreover, the subject may be at risk of contracting a viral infection due to proximity to an outbreak of disease, e.g., the subject lives in a densely populated city or in close proximity to subjects with confirmed or suspected viral infection, or due to choice of work, e.g., a worker hospitals, pharmaceutical researcher, traveler to a hotspot, or frequent flyer.

To treat or treat means the administration of an anti-CoV-S antigen-binding protein, e.g., an antibody or antigen-binding fragment according to the present invention (e.g., from Table 1) to a subject characterized by the presence of one or more signs or symptoms of a disease or infection, e.g., a viral infection, for which the antigen binding protein is effective when administered to a subject in an effective or therapeutically effective amount or dose (as discussed herein).

The present invention also includes prophylactic administration of an anti-CoV-S antigen binding protein, for example, an antibody or an antigen binding fragment thereof according to the present invention (eg, from Table 1), to a subject at risk of a viral infection, for the purpose of preventing such infection. Passive antibody-based immunoprophylaxis has proven effective in preventing viral infection in a subject. See, for example, Berry et al., Passive broadspectrum influenza immunoprophylaxis. Influenza Res Treat. 2014; 2014:267594. Epub 2014 Sep 22; and Jianqiang et al., Passive immune neutralization strategies for prevention and control of influenza A infections, Immunotherapy. February 2012; 4(2): 175-186; Prabhu et al., Antivir Ther. 2009; 14(7):911-21, Prophylactic and therapeutic efficacy of a chimeric monoclonal antibody specific for H5 hemagglutinin against lethal H5N1 influenza. To prevent or prophylaxis means to administer to a subject an anti-CoV-S antigen-binding protein, such as an antibody or antigen-binding fragment of the present invention (e.g., from Table 1) for the purpose of suppressing the manifestation of a disease or infection (e.g., a viral infection) in the body of the subject for which the antigen-binding the protein is effective when administered to a subject in an effective or therapeutically effective amount or dose (as discussed herein).

In an embodiment of the present invention, a sign or symptom of a viral infection in a subject is the survival or spread of the virus in the subject's body, for example, as determined by a viral titer assay (e.g., spread of coronavirus in embryonated chicken eggs or coronavirus spike protein assay). This document discusses other signs and symptoms of viral infection.

As noted above, in some embodiments, the subject may be a non-human animal, and the antigen binding proteins (e.g., antibodies and antigen binding fragments) discussed herein may be used in a veterinary context to treat and/or prevent a disease in animals, not that are human (for example, cats, dogs, pigs, cows, horses, goats, rabbits, sheep, etc.).

The present invention provides a method of treating or preventing a viral infection (for example, coronavirus infection) or inducing regression, elimination or suppression of the progression of at least one sign or symptom of a viral infection, for example:

fever or sensations of fever/chills;

cough;

sore throat;

runny or stuffy nose;

sneezing;

muscle or body pain;

headache;

- 36 044746 fatigue;

vomiting;

diarrhea;

respiratory tract infections;

chest discomfort;

shortness of breath;

bronchitis; and/or pneumonia, wherein said sign or symptom is secondary to a viral infection in a subject in need thereof (e.g., a human), by administering to the subject a therapeutically effective amount of anti-CoV-S antigen binding protein (e.g., from Table 1), for example, by injecting the protein into the subject's body.

Combinations and pharmaceutical compositions.

To prepare pharmaceutical compositions of antigen binding proteins against CoV-S, for example, antibodies and antigen binding fragments thereof (for example, from Table 1), the antigen binding protein is mixed with a pharmaceutically acceptable carrier or excipient. See, for example, Remington's Pharmaceutical Sciences and U.S. Pharmacopeia: National Formulary, Mack Publishing Company, Easton, Pa. (1984); Hardman, et al. (2001) Goodman and Gilman's The Pharmacological Basis of Therapeutics, McGraw-Hill, New York, N.Y.; Gennaro (2000) Remington: The Science and Practice of Pharmacy, Lippincott, Williams, and Wilkins, New York, N.Y.; Avis, et al. (eds.) (1993) Pharmaceutical Dosage Forms: Parenteral Medications, Marcel Dekker, NY; Lieberman, et al. (eds.) (1990) Pharmaceutical Dosage Forms: Tablets, Marcel Dekker, NY; Lieberman, et al. (eds.) (1990) Pharmaceutical Dosage Forms: Disperse Systems, Marcel Dekker, NY; Weiner and Kotkoskie (2000) Excipient Toxicity and Safety, Marcel Dekker, Inc., New York, N.Y. In an embodiment of the present invention, the pharmaceutical composition is sterile. Such compositions are included in the present invention.

The present invention includes dehydrated, for example, lyophilized compositions containing antigen-binding proteins against CoV-S, for example, an antibody or antigen-binding fragment thereof (for example, from Table 1), or a pharmaceutical composition thereof containing a pharmaceutically acceptable carrier, but substantially free of water.

In a further embodiment of the present invention, an additional therapeutic agent that is administered to a subject in combination with an anti-CoV-S antigen binding protein, e.g., an antibody or antigen binding fragment thereof (e.g., from Table 1) described herein is administered to the subject in accordance with Physicians ' Desk Reference 2003 (Thomson Healthcare; ^57th edition (Nov. 1, 2002)).

The route of administration may vary. Routes of administration include oral, rectal, transmucosal, intestinal, parenteral; intramuscular, subcutaneous, intradermal, intramedullary, intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, intraocular, inhalation, insufflation, topical, cutaneous, transdermal or intra-arterial.

The present invention provides methods for administering an anti-CoVS antigen binding protein, such as an antibody or an antigen binding fragment thereof (eg, from Table 1), comprising administering the protein to a subject. For example, the method includes puncturing the subject's body with a syringe needle and injecting an antigen binding protein into the subject's body, for example, into a vein, artery, tumor, muscle tissue or subcutaneous tissue of the subject.

The present invention provides a vessel (for example, a plastic or glass vial, for example with a cap, or a chromatography column, a hollow needle or a syringe barrel) containing any of the antigen-binding proteins against CoV-S, for example, antibodies or antigen-binding fragments thereof (for example, from Table 1), polypeptides (for example, HC, LC, V _H or V _L from Table 1) or polynucleotides (for example, from Table 2) or vectors provided herein, or a pharmaceutical composition thereof containing a pharmaceutically acceptable carrier .

In an embodiment of the present invention, an anti-CoV-S antigen binding protein, for example, an antibody or antigen binding fragment thereof according to the present invention (eg, from Table 1) is administered in combination with one or more additional therapeutic agents. The additional therapeutic agent includes, but is not limited to: an anti-inflammatory agent, an antimalarial agent, a second antibody or an antigen binding fragment thereof that specifically binds TMPRSS2, and a second antibody or an antigen binding fragment thereof that specifically binds CoV-S. In some embodiments, the antimalarial agent is chloroquine or hydroxychloroquine. In some embodiments, the anti-inflammatory agent is an antibody, such as sarilumab, tocilizumab, or gimsilumab. In some embodiments, the additional therapeutic agent is a second antibody or antigen binding fragment described herein, for example, from table. 1. In some embodiments, one, two, three, four or more antibodies or antigen-binding fragments thereof from Table. 1 can be entered

- 37 044746 in combination (for example, simultaneously or sequentially). Specific combinations of antibodies from the table. 1 are listed in table. typical antibody combinations below (with each number representing a specific combination, for example, mAb10989 and mAb10987 are combination 1, mAb10989 and mAb10934 are combination 2, etc.). In some embodiments, the combination of antibodies can be selected from antibodies that bind to different epitope clusters. For example, certain antibodies described herein belong to the following epitope clusters: cluster 1 - mAb10987, mAb10922, mAb10936 and mAb10934; cluster 2 - mAb10989, mAb10977 and mAb10933; cluster 3 - mAb10920; cluster 4 - mAb10954, mAb10986 and mAb10964; and cluster 5 mAb10984. Thus, the combination of two antibodies can be selected, for example, from cluster 1 and cluster 2, cluster 1 and cluster 3, cluster 1 and cluster 4, cluster 1 and cluster 5, cluster 2 and cluster 3, cluster 2 and cluster 4, cluster 2 and cluster 5, cluster 3 and cluster 4, cluster 3 and cluster 5, and cluster 4 and cluster 5. In some embodiments, the antibody that specifically binds TMPRSS2 is H1H7017N, as described in International Patent Publication No. WO/2019/147831.

Table of typical antibody combinations.

mAT 10989 mAT 10987 mAT 10934 mAT 10933 mAT 10920 mAT 10922 mAT 10936 mAT 10954 mAT 10964 mAT 10977 mAT 10984 mAT 10986 mAT 10989 X 1 2 3 4 5 6 7 8 9 10 AND mAT 10987 12 X 13 14 15 16 17 18 19 20 21 22 mAT 10934 23 24 X 25 26 27 28 29 thirty 31 32 33 mAT 10933 34 35 36 X 37 38 39 40 41 42 43 44 mAT 10920 45 46 47 48 X 49 50 51 52 53 54 55 mAT 10922 56 57 58 59 60 X 61 62 63 64 65 66 mAT 10936 67 68 69 70 71 72 X 73 74 75 76 77 mAT 10954 78 79 80 81 82 83 84 X 85 86 87 88 mAT 10964 89 90 91 92 93 94 95 96 X 97 98 99 mAT 10977 100 101 102 103 104 105 106 107 108 X 109 110 mAT 10984 111 112 FROM 114 115 116 117 118 119 120 X 121 mAT 10986 122 123 124 125 126 127 128 129 130 131 132 X

In some embodiments, anti-CoV-S antigen-binding proteins (e.g., anti-SARS-CoV-2-S antibodies or antigen-binding fragments thereof) from different human donors can be combined. The present invention includes a composition comprising two (or more) anti-SARS-CoV-2-S antibodies or antigen-binding fragments containing variable domains from human subjects, wherein said two (or more) antibodies or antigen-binding fragments are derived from different subjects (e.g., two different human subjects). Variable regions of antibodies derived from human B cells are discussed, for example, in Examples 1 and 2 (Table 3), where variable domains cloned from such B cells are described to be combined with a constant region not derived from these B cells. -cells, receiving hybrid antibodies. The source (donor) of such antibody variable regions is shown below in the table of typical antibody variable regions of human origin. In some embodiments, the composition may comprise a combination of an antibody or antigen binding fragment thereof with variable domains obtained from Donor 1 and an antibody or antigen binding fragment thereof with variable domains obtained from Donor 2. In some embodiments, the composition may contain a combination of an antibody or antigen binding fragment thereof with variable domains obtained from donor 1, and an antibody or antigen-binding fragment thereof with variable domains obtained from donor 3. In some embodiments, the composition may comprise a combination of an antibody or antigen-binding fragment thereof with variable domains obtained from donor 2, and an antibody or its antigen binding fragment with variable domains obtained from donor 3. In some embodiments, the composition may contain a combination of mAb10987 (for example, an antibody containing the CDR, variable region, or heavy and light chain sequences shown in Table 1) from donor 1 and mAb10989 (e.g., antibodies, CDR sequences, variable regions, or heavy and light chains shown in Table 1) from donor 3.

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Table of typical variable regions of antibodies of human origin. mAT Donor mAT Donor mAT10954 Donor 3 mAT10955 Donor 3 mAT10956 Donor 3 mAT10957 Donor 3 mAT10964 Donor 1 mAT10965 Donor 2 mAT10966 Donor 3 mAT10967 Donor 3 mAT10 970 Donor 1 mAT10971 Donor 1 mAT10977 Donor 1 mAT10984 Donor 1 mAT10985 Donor 1 mAT10986 Donor 1 mAT10987 Donor 1 mAT10988 Donor 3 mAT10989 Donor 3 mAT10969 Donor 1

In some embodiments, the additional therapeutic agent is an antiviral drug and/or a vaccine. As used herein, the term antiviral drug refers to any drug or therapeutic agent used to treat, prevent, or attenuate a viral infection in a subject. The term antiviral drug includes, but is not limited to, a cationic steroidal antimicrobial agent, leupeptin, aprotinin, ribavirin, or interferon-alpha2b. Methods for treating or preventing a viral (eg, coronavirus) infection in a subject in need of said treatment or prevention by administering an antibody or antigen-binding fragment from Table. 1 in combination with an additional therapeutic agent are included in the present invention.

For example, in an embodiment of the present invention, the additional therapeutic agent is a vaccine, such as a coronavirus vaccine. In an embodiment of the present invention, the vaccine is an inactivated/killed virus vaccine, a live attenuated virus vaccine, or a subunit virus vaccine.

For example, in an embodiment of the present invention, the additional therapeutic agent is:

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See Shen et al. Biochimie 142: 1-10 (2017).

In an embodiment of the present invention, the antiviral drug is an antibody or antigen-binding fragment that specifically binds to a coronavirus, for example, SARS-CoV-2, SARS-CoV or MERS-CoV. Examples of antibodies against CoV-S include: H4sH15188P; Н1Н15188Р; H1H15211P; H1H15177P; H4sH15211P; H1H15260P2; H1H15259P2; H1H15203P; H4sH15260P2; H4sH15231P2; H1H15237P2; H1H15208P; H1H15228P2; H1H15233P2; H1H15264P2; H1H15231P2; H1H15253P2; H1H15215P; and H1H15249P2 presented in International Patent Application Publication No. WO/2015/179535, or an antigen binding fragment thereof, for example, wherein said antibody or fragment comprises an immunoglobulin light chain containing CDR-L1, CDR-L2 and CDR-L3 (for example, V _L or its light chain); and a heavy chain comprising CDR-H1, CDR-H2 and CDR-H3 (eg, VH or a heavy chain thereof) of, but not limited to, any of the above anti-CoV-S antibodies.

In a certain embodiment of the present invention, the additional therapeutic agent is not an aprotinin, leupeptin, a cationic steroidal antimicrobial agent, an influenza vaccine (e.g., killed, live, attenuated whole virus, or subunit vaccine), or an anti-influenza virus antibody (e.g., an anti-hemagglutinin antibody) ).

The term in combination with indicates that the anti-CoVS antigen-binding protein components, e.g., an antibody or antigen-binding fragment thereof of the present invention, together with another agent, e.g., chloroquine, can be formulated as a single composition, e.g., for simultaneous delivery or formulated separately in the form of two or more compositions (for example, a set). Each component can be administered to a subject at a time different from the time of administration of the other component; for example, each administration may be performed non-simultaneously (eg, separately or sequentially) at intervals over a predetermined period of time. Moreover, the individual components can be administered to the subject by the same or a different route (for example, an anti-CoV-S antibody or an antigen-binding fragment thereof.

Sets.

In addition, the present invention provides kits containing one or more components that include, but are not limited to, an anti-CoV-S antigen binding protein, such as, but not limited to, an antibody or antigen binding fragment discussed herein (e.g., from Table 1), in association with one or more additional components, including, but not limited to, an additional therapeutic agent discussed herein. The antigen binding protein and/or additional therapeutic agent can be formulated as a single composition or separately in two or more compositions, for example, with a pharmaceutically acceptable carrier in a pharmaceutical composition.

In one embodiment of the present invention, the kit contains an antigen binding protein against CoV-S, for example, an antibody or antigen binding fragment thereof according to the present invention (for example, from Table 1), or a pharmaceutical composition thereof in a single container (for example, in a sterile glass or plastic vial ) and an additional therapeutic agent in another container (eg, a sterile glass or plastic vial).

In yet another embodiment, the kit contains a combination according to the present invention containing an antigen binding protein against CoV-S, for example, an antibody or antigen binding fragment according to the present invention (for example, from Table 1), or a pharmaceutical composition thereof in combination with one or more additional therapeutic agents formulated together, optionally in a pharmaceutical composition, in a single common container.

If the kit contains a pharmaceutical composition for parenteral administration to a subject, the kit may contain a device (eg, an injection device) for performing such administration. For example, the kit may include one or more hypodermic needles or other injection devices discussed above containing an anti-CoV-S antigen binding protein, for example, an antibody or antigen binding fragment thereof according to the present invention (eg, from Table 1).

The kit may contain an insert containing information about the pharmaceutical compositions and dosage forms present in the kit. Generally, such information will assist patients and physicians in using the included pharmaceutical compositions and dosage forms effectively and safely. For example, the package insert may provide the following information regarding the combination of the present invention: pharmacokinetics, pharmacodynamics, clinical studies, efficacy parameters, indications and use, contraindications, warnings, precautions, adverse reactions, overdose, proper dosage and administration, type of supply, appropriate storage conditions, links, manufacturer/distributor information and patent information.

Diagnostic use of antibodies.

Antigen-binding proteins against CoV-S, for example, antibodies or antigen-binding fragments thereof according to the present invention (for example, from Table 1) can be used to detect and/or measure CoV-S in a sample. Typical CoV-S assays may involve, for example, contacting a sample with an anti-CoV-S antigen binding protein according to the present invention, wherein the anti-CoV-S antigen binding protein is labeled with a detectable tag or reporter molecule or is used as a capture ligand for selective isolation of CoV-S from samples. The presence of anti-CoV-S antigen binding protein in complex with CoV-S indicates the presence of CoV-S in the sample. Alternatively, an unlabeled antibody may be used for diagnostic purposes in combination with a secondary antibody that is itself labeled with a detectable label. The detectable label or reporter molecule may be a radioactive isotope, for example, ³ H, ¹⁴ C, ³² P, ³⁵ S or ¹²⁵ I; a fluorescent or chemiluminescent group, for example fluorescein isothiocyanate or rhodamine; or an enzyme, for example alkaline phosphatase, β-galactosidase, horseradish peroxidase or luciferase. Specific typical assays that can be used to detect or measure

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CoV-S in a sample include neutralization assays, enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), and fluorescence-activated cell sorting (FACS). Thus, the present invention includes a method for detecting the presence of a spike protein polypeptide in a sample, comprising contacting the sample with an anti-CoV-S antigen binding protein and detecting the presence of a CoV-S/anti-CoV-S antigen binding protein complex, the presence of the complex indicating the presence of CoV-S. S.

The anti-CoV-S antigen binding protein of the present invention (eg, from Table 1) can be used in a Western blot or immunoblotting procedure to detect the presence of CoV-S or a fragment thereof in a sample. Such a procedure is part of the present invention and includes steps, for example:

(1) providing a membrane or other solid support containing a sample to be analyzed for the presence of CoV-S, for example, optionally including the step of transferring proteins from the sample to be analyzed for the presence of CoV-S (for example, after electrophoretic separation of proteins in the sample by PAGE or SDS-PAGE) onto a membrane or other solid support using a method known in the art (eg, semi-dry blotting or reservoir blotting); and contacting a membrane or other solid support to be assayed for the presence of CoV-S or a fragment thereof with an anti-CoV-S antigen binding protein of the present invention.

Such a membrane may take the form of, for example, a nitrocellulose or vinyl polymer membrane (e.g., polyvinylidene fluoride (PVDF)) onto which the proteins to be analyzed for the presence of CoV-S are transferred in a non-denaturing PAGE (polyacrylamide gel) or SDS-PAGE ( polyacrylamide gel with sodium dodecyl sulfate) (for example, after electrophoretic separation in the gel). Before bringing the membrane into contact with the antigen binding protein against CoV-S, the membrane is optionally blocked, for example, with nonfat dry milk or the like. for the purpose of binding nonspecific protein binding sites on the membrane.

(2) washing the membrane one or more times to remove unbound antigen-binding protein against CoV-S and other unbound substances; and (3) detection of associated antigen-binding protein against CoV-S.

Detection of bound antigen binding protein indicates the presence of CoV-S protein on the membrane or support and in the sample. Detection of bound antigen binding protein can be accomplished by binding the antigen binding protein to a secondary antibody (anti-immunoglobulin antibody) labeled with a detectable label, and then detecting the presence of the secondary antibody label.

The anti-CoV-S antigen binding proteins described herein (eg, antibodies and antigen binding fragments (eg, from Table 1)) can also be used for immunohistochemical analysis. Such a method is included in the present invention and includes, for example, (1) contacting tissue to be analyzed for the presence of CoV-S protein with an anti-CoV-S antigen binding protein according to the present invention; and (2) detection of antigen binding protein on or in the tissue.

If the antigen binding protein itself is labeled with a detectable label, it can be detected directly. Alternatively, the antigen binding protein can be coupled to a secondary antibody labeled with a detectable label, and detection of the label is then performed.

Examples

The following examples are provided to provide those skilled in the art with a complete description of the preparation and use of the methods and compositions of the present invention, and are not intended to limit the spirit of what the inventors of the present invention believe to be their invention. The authors have made efforts to ensure accuracy in terms of the numbers used (e.g., quantity, temperature, etc.), but some experimental errors and biases should be taken into account. Unless otherwise noted, parts are parts by weight, molecular weight is average molecular weight, temperature is in degrees Celsius, room temperature is approximately 25°C, and pressure is at or near atmospheric pressure.

Example 1: Production of human antibodies against the SARS-CoV-2 spike protein (SARS-CoV-2-S).

Antibodies to the SARS-CoV-2-Spike protein (SARS-COV-2-S) were generated in VELOCIMMUNE® mice containing DNA encoding human immunoglobulin kappa heavy and light chain variable regions or lambda heavy and light chain variable regions human immunoglobulin. Each mouse was immunized with a vector expressing the receptor binding domain (RBD) of SARS-CoV-2-S (amino acids 1-1273, NCBI accession number (MN908947.3), SEQ ID NO: 832), followed by a secondary challenge using the SARS-CoV-2-S vector. CoV-2-S or SARS-CoV-2S protein. The antibody-based immune response was monitored using a SARS-CoV-2-S-specific immunoassay. After achieving the desired immune response, splenocytes were collected and fused with mouse myeloma cells to maintain their viability and form hybrocytes.

- 42 044746 local lines. Hybridoma cell lines were screened and selected to identify cell lines that produce antibodies specific to SARS-CoV-2-S. Antibodies against SARSCoV-2-S were also isolated directly from antigen-positive mouse B cells without fusion with myeloma cells, as described in US Pat. No. 7,582,298, expressly incorporated herein by reference in its entirety. Using this method, fully human antibodies against SARS-CoV-2-S (ie, antibodies containing human variable domains and human constant domains) were obtained.

Antibody variable regions have also been isolated from human blood samples. Whole blood was obtained from patients 3–4 weeks after laboratory-confirmed positive SARS-CoV-2 PCR and symptomatic COVID-19 disease. RBCs were lysed using ammonium chloride lysis buffer (Life Technologies), and B cells were enriched by negative selection. Single B cells that bound the SARS-CoV-2 spike protein were isolated using fluorescence-activated cell sorting (FACS). Isolated B cells were seeded into single-well plates and mixed with PCR primers specific for the variable regions of the light and heavy chains of the antibody. cDNA for each individual B cell was synthesized using a reverse transcriptase (RT) reaction. Each resulting RT product was then separated and transferred into two appropriate wells for subsequent PCR analysis of the antibody heavy and light chains. One set of the resulting RT products was first amplified by PCR using a degenerate 5' primer specific for the antibody heavy chain variable region leader sequence or a degenerate 5' primer specific for the antibody light chain variable region leader sequence and 3' -primer specific for the constant region of the antibody to form an amplicon. The amplicons were then reamplified by PCR using a degenerate 5' primer specific for antibody heavy chain variable region framework 1 or a degenerate 5' primer specific for antibody light chain variable framework 1 and 3' -primer specific for the constant region of the antibody to form amplicons for cloning. The antibody heavy chain and light chain PCR products were cloned into expression vectors containing a heavy chain constant region and a light chain constant region, respectively, thereby obtaining hybrid antibody expression vectors. Vectors expressing full-length heavy and light chain pairs were transfected into CHO cells to produce antibody proteins for analysis.

The biological properties of exemplary antibodies produced in accordance with the methods described in this example are described in detail in the examples set forth below.

Example 2. Amino acid and nucleotide sequences of the variable regions of the heavy and light chains.

In table Figure 1 shows identifiers of the amino acid sequences of the variable regions of the heavy and light chains and CDRs, as well as the sequences of the heavy and light chains of typical antibodies against SARS-CoV-2-S. The corresponding identifiers of nucleotide sequences are presented in table. 2.

Table 1 ________Aino acid sequence identifiers________

SEQ ID NO Labeled non-antibodies HCVB HCDR 1 HCDB 2 HCDB 3 LCVR LCDR 1 LCDR 2 LCDR 3 HC L.C. mAT10913 2 4 6 8 10 12 14 16 18 20 mAT10915 22 24 26 28 thirty 32 34 36 38 40 mAT10916 2 4 6 8 10 12 14 16 42 20 mAT10917 44 46 26 49 51 53 55 57 59 61 mAT10918 22 24 26 28 thirty 32 34 36 63 40 mAT10920 65 67 69 71 73 75 55 77 79 81 mAT10921 83 85 26 87 89 91 55 93 95 97

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mAT10922 99 101 103 105 107 109 111 FROM 115 117 mAT10923 119 121 123 125 127 129 55 131 133 135 mAT10924 137 139 141 143 145 147 149 151 153 155 mAT10925 65 67 69 71 73 75 55 77 157 81 mAT10926 83 85 26 87 89 91 55 93 159 97 mAT10927 99 101 103 105 107 109 111 FROM 161 117 mAT10928 119 121 123 125 127 129 55 131 163 135 mAT10929 137 139 141 143 145 147 149 151 165 155 mAT 10930 167 169 171 173 175 129 55 177 179 181 mAT10931 167 169 171 173 175 129 55 177 183 181 mAT10932 185 187 26 189 191 75 194 196 198 200 mAT 10933 202 204 206 208 210 212 55 214 216 218 mAT10934 220 222 224 226 228 230 194 232 234 236 mAT10935 238 24 26 240 242 244 194 246 248 250 mAT10936 252 254 256 258 260 129 55 262 264 266 mAT10937 268 270 272 274 276 129 55 278 280 282 mAT10940 284 169 286 288 290 292 294 296 298 300 mAT10938 302 24 26 304 306 308 194 310 312 314 mAT10939 316 187 319 321 323 325 55 327 329 331 mAT10941 333 85 26 336 338 340 294 296 342 344 mAT10942 185 187 26 189 191 75 194 196 346 200 mAT10943 202 204 206 208 210 212 55 214 348 218 mAT10944 220 222 224 226 228 230 194 232 350 236 mAT10945 238 24 26 240 242 244 194 246 352 250 mAT10946 252 254 256 258 260 129 55 262 354 266 mAT10947 268 270 272 274 276 129 55 278 356 282 mAT10948 302 24 26 304 306 308 194 310 358 314 mAT10949 316 187 319 321 323 325 55 327 360 331 mAT10951 333 85 26 336 338 340 294 296 362 344 mAT10950 284 169 286 288 290 292 294 296 364 300 mAT10954 366 85 26 370 372 244 194 375 377 379 mAT10955 381 383 26 385 387 389 194 310 392 394 mAT10956 396 187 26 399 401 389 194 403 405 407 mAT10957 409 411 26 414 416 53 55 418 420 422

-44044746

mAT10958 366 85 26 370 372 244 194 375 424 379 mAT10959 381 383 26 385 387 389 194 310 426 394 mAT10960 396 187 26 399 401 389 194 403 428 407 mAT10961 409 411 26 414 416 53 55 418 430 422 mAT10964 432 434 436 438 440 442 55 445 447 449 mAT10965 451 453 26 455 457 459 34 462 464 466 mAT10966 468 187 26 470 472 389 194 474 476 478 mAT10967 480 24 483 485 487 389 194 489 491 493 mAT10969 495 497 499 501 503 389 194 214 506 508 mAT10970 510 24 26 512 514 516 194 518 520 522 mAT10971 524 411 26 528 530 532 55 534 536 538 mAT10973 432 434 436 438 440 442 55 445 540 449 mAT10974 451 453 26 455 457 459 34 462 542 466 mAT10975 468 187 26 470 472 389 194 474 544 478 mAT10976 480 24 483 485 487 389 194 489 546 493 mAT10977 548 550 552 554 556 558 294 560 562 564 mAT10978 495 497 499 501 503 389 194 214 566 508 mAT10979 510 24 26 512 514 516 194 518 568 522 mAT10980 524 411 26 528 530 532 55 534 570 538 mAT10981 548 550 552 554 556 558 294 560 572 564 mAT10982 574 187 576 578 580 582 584 586 588 590 mAT10983 574 187 576 578 580 582 584 586 592 590 mAT10984 594 596 26 598 600 12 14 602 604 606 mAT10985 608 169 610 612 614 616 584 618 620 622 mAT10986 624 626 26 628 630 582 632 634 636 638 mAT10987 640 642 499 644 646 648 650 652 654 656 mAT10988 658 660 662 664 666 668 670 672 674 676 mAT10989 678 680 682 684 686 688 650 690 692 694 mAT10990 594 596 26 598 600 12 14 602 696 606 mAT10991 608 169 610 612 614 616 584 618 698 622 mAT10992 624 626 26 628 630 582 632 634 700 638 mAT10993 640 642 499 644 646 648 650 652 702 656 mAT10994 658 660 662 664 666 668 670 672 704 676 mAT10995 678 680 682 684 686 688 650 690 706 694

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mAT10996 708 24 26 711 713 129 55 715 717 719 mAT10997 708 24 26 711 713 129 55 715 721 719 mAT10998 723 187 26 725 727 129 55 729 731 733 mAT10999 723 187 26 725 727 129 55 729 735 733 mATPOOO 737 24 26 739 741 743 55 745 747 749 mAT11001 737 24 26 739 741 743 55 745 751 749 mAT11002 753 24 26 755 713 129 55 715 757 719 MATHI 753 24 26 755 713 129 55 715 759 719 mAT10914 44 46 26 49 51 53 55 57 762 61 mAT11004 764 766 499 768 770 91 55 772 774 776 mAT11005 764 766 499 768 770 91 55 772 778 776 mAT11006 780 782 26 784 786 53 55 788 790 792 mAT11007 780 782 26 784 786 53 55 788 794 792 mAT11008 796 24 26 798 800 53 55 802 804 806 mAT11009 796 24 26 798 800 53 55 802 808 806 MATIOYU 810 812 814 816 818 129 820 822 824 826 mat! 1011 810 812 814 816 818 129 820 822 828 826

table 2

Nucleotide sequence identifiers

SEQ ID NO Labeled non-antibodies HCVB HCDB 1 HCDB 2 HCDB 3 LCVB LCDB 1 LCDB 2 LCDB 3 HC L.C. mAT10913 1 h 5 7 9 eleven 13 15 17 19 mAT10915 21 23 25 27 29 31 33 35 37 39 mAT10916 1 h 5 7 9 eleven 13 15 41 19 mAT10917 43 45 47 48 50 52 54 56 58 60 mAT10918 21 23 25 27 29 31 33 35 62 39 mAT10920 64 66 68 70 72 74 54 76 78 80 mAT10921 82 84 47 86 88 90 54 92 94 96 mAT10922 98 100 102 104 106 108 110 112 114 116 mAT10923 118 120 122 124 126 128 54 130 132 134 mAT10924 136 138 140 142 144 146 148 150 152 154 mAT10925 64 66 68 70 72 74 54 76 156 80 mAT10926 82 84 47 86 88 90 54 92 158 96

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mAT10927 98 100 102 104 106 108 110 112 160 116 mAT10928 118 120 122 124 126 128 54 130 162 134 mAT10929 136 138 140 142 144 146 148 150 164 154 mAT10930 166 168 170 172 174 128 54 176 178 180 mAT 10931 166 168 170 172 174 128 54 176 182 180 mAT10932 184 186 47 188 190 192 193 195 197 199 mAT 10933 201 203 205 207 209 211 54 213 215 217 mAT10934 219 221 223 225 227 229 193 231 233 235 mAT10935 237 23 47 239 241 243 193 245 247 249 mAT10936 251 253 255 257 259 128 54 261 263 265 mAT10937 267 269 271 273 275 128 54 277 279 281 mAT10940 283 168 285 287 289 291 293 295 297 299 mAT10938 301 23 47 303 305 307 193 309 311 313 mAT10939 315 317 318 320 322 324 54 326 328 330 mAT10941 332 334 47 335 337 339 293 295 341 343 mAT10942 184 186 47 188 190 192 193 195 345 199 mAT10943 201 203 205 207 209 211 54 213 347 217 mAT10944 219 221 223 225 227 229 193 231 349 235 mAT10945 237 23 47 239 241 243 193 245 351 249 mAT10946 251 253 255 257 259 128 54 261 353 265 mAT10947 267 269 271 273 275 128 54 277 355 281 mAT10948 301 23 47 303 305 307 193 309 357 313 mAT10949 315 317 318 320 322 324 54 326 359 330 mAT10951 332 334 47 335 337 339 293 295 361 343 mAT10950 283 168 285 287 289 291 293 295 363 299 mAT10954 365 367 368 369 371 373 193 374 376 378 mAT10955 380 382 47 384 386 388 193 390 391 393 mAT10956 395 397 47 398 400 388 193 402 404 406 mAT10957 408 410 412 413 415 52 54 417 419 421 mAT10958 365 367 368 369 371 373 193 374 423 378 mAT10959 380 382 47 384 386 388 193 390 425 393 mAT10960 395 397 47 398 400 388 193 402 427 406 mAT10961 408 410 412 413 415 52 54 417 429 421 mAT10964 431 433 435 437 439 441 443 444 446 448

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mAT10965 450 452 47 454 456 458 460 461 463 465 mAT10966 467 397 412 469 471 388 193 473 475 477 mAT10967 479 481 482 484 486 388 193 488 490 492 mAT10969 494 496 498 500 502 388 193 504 505 507 mAT10970 509 481 412 511 513 515 193 517 519 521 mAT10971 523 525 526 527 529 531 54 533 535 537 mAT10973 431 433 435 437 439 441 443 444 539 448 mAT10974 450 452 47 454 456 458 460 461 541 465 mAT10975 467 397 412 469 471 388 193 473 543 477 mAT10976 479 481 482 484 486 388 193 488 545 492 mAT10977 547 549 551 553 555 557 293 559 561 563 mAT10978 494 496 498 500 502 388 193 504 565 507 mAT10979 509 481 412 511 513 515 193 517 567 521 mAT10980 523 525 526 527 529 531 54 533 569 537 mAT10981 547 549 551 553 555 557 293 559 571 563 mAT10982 573 186 575 577 579 581 583 585 587 589 mAT10983 573 186 575 577 579 581 583 585 591 589 mAT10984 593 595 47 597 599 AND 13 601 603 605 mAT10985 607 168 609 611 613 615 583 617 619 621 mAT10986 623 625 47 627 629 581 631 633 635 637 mAT10987 639 641 498 643 645 647 649 651 653 655 mAT10988 657 659 661 663 665 667 669 671 673 675 mAT10989 677 679 681 683 685 687 649 689 691 693 mAT10990 593 595 47 597 599 AND 13 601 695 605 mAT10991 607 168 609 611 613 615 583 617 697 621 mAT10992 623 625 47 627 629 581 631 633 699 637 mAT10993 639 641 498 643 645 647 649 651 701 655 mAT10994 657 659 661 663 665 667 669 671 703 675 mAT10995 677 679 681 683 685 687 649 689 705 693 mAT10996 707 709 47 710 712 128 54 714 716 718 mAT10997 707 709 47 710 712 128 54 714 720 718 mAT10998 722 186 47 724 726 128 54 728 730 732 mAT10999 722 186 47 724 726 128 54 728 734 732 mATPOOO 736 23 47 738 740 742 54 744 746 748 mAT11001 736 23 47 738 740 742 54 744 750 748 mAT11002 752 23 47 754 712 128 54 714 756 718 mAT11003 752 23 47 754 712 128 54 714 758 718 mAT10914 760 45 47 48 50 52 54 56 761 60 mAT11004 763 765 498 767 769 90 54 771 773 775 mAT11005 763 765 498 767 769 90 54 771 777 775 mATIOOb 779 781 47 783 785 52 54 787 789 791 mAT11007 779 781 47 783 785 52 54 787 793 791 mAT11008 795 709 47 797 799 52 54 801 803 805 mAT11009 795 709 47 797 799 52 54 801 807 805 mAT11010 809 811 813 815 817 128 819 821 823 825 mat! 1011 809 811 813 815 817 128 819 821 827 825

The antibodies described herein contain fully human variable regions, but may contain mouse constant regions (for example, mouse IgG1 Fc or mouse IgG2 Fc

- 48 044746 (isotype a or b)) or human constant regions (for example, human IgG1 Fc or human IgG4 Fc). As one skilled in the art will appreciate, an antibody characterized by a particular Fc isotype can be converted to an antibody with a different Fc isotype (e.g., a mouse IgG1 Fc antibody can be converted to a human IgG4 antibody, etc.), however, in any case, the variable domains (including CDRs) indicated by the numeric identifiers shown in Table. 1 and 2 will remain unchanged and the antigen binding properties are expected to be identical or substantially similar regardless of the nature of the constant domain.

The variable regions of antibodies obtained from VELOCIMMUNE® mice and from human samples were sequenced using next generation sequencing and revealed a repertoire for heavy and light chain pairs (Fig. 10A and 10B). The predominant antibody lineage VI used VH3-53 paired with VK1-9, VK1-33, or VK1-39, whereas human antibodies used VH3-66 paired with VK1-33 or VH2-70 paired with VK1-39. Further analysis of the overlay sequences demonstrated a significant degree of overlap in the repertoire of isolated kappa chains between VI and human derived antibodies. Although the lambda circuit repertoire match was not as good, this may be due to the fact that this study only included two lambda circuit mice. The average heavy chain CDR length was similar for antibodies derived from VI and humans, being 13 and 14.5 amino acids, respectively. The average CDR length of the kappa chain was similar for antibodies derived from VI and humans, being 9 amino acids, and was similar to the values for the lambda chains, which were 11.1 and 10.6 amino acids, respectively. The availability of humanized mouse and human antibodies has allowed for increased diversity of V genes and the subsequent identification of noncompetitive antibodies.

As described above, antibodies were generated from hybridomas obtained from VELOCIMMUNE® mice, by direct isolation from antigen-positive VELOCIMMUNE® mouse B cells or from variable regions cloned from antigen-positive human B cells. Summary information on these sources is presented in table. 3.

Table 3

Antibody/variable region sources

Antibody Source mAT10913 Mouse B cells mAT10915 Mouse B cells mAT10916 Mouse B cells mAT10917 Mouse B cells mAT10918 Mouse B cells mAT10920 Mouse B cells mAT10921 Mouse B cells mAT10922 Mouse B cells mAT10923 Mouse B cells mAT10924 Mouse B cells mAT10925 Mouse B cells mAT10926 Mouse B cells mAT10927 Mouse B cells mAT10928 Mouse B cells mAT10929 Mouse B cells mAT 10930 Mouse B cells mAT10931 Mouse B cells

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mAT10932 Mouse B cells mAT 10933 Mouse B cells mAT10934 Mouse B cells mAT10935 Mouse B cells mAT10936 Mouse B cells mAT10937 Mouse B cells mAT 10940 Mouse B cells mAT10938 Mouse B cells mAT10939 Mouse B cells mAT 10941 Mouse B cells mAT10942 Mouse B cells mAT10943 Mouse B cells mAT10944 Mouse B cells mAT10945 Mouse B cells mAT10946 Mouse B cells mAT10947 Mouse B cells mAT10948 Mouse B cells mAT10949 Mouse B cells mAT10951 Mouse B cells mAT10950 Mouse B cells mAT10954 Human B cells mAT10955 Human B cells mAT10956 Human B cells mAT10957 Human B cells mAT10958 Human B cells mAT10959 Human B cells mAT10960 Human B cells mAT10961 Human B cells mAT10964 Human B cells mAT10965 Human B cells mAT10966 Human B cells mAT10967 Human B cells mAT10969 Human B cells mAT10970 Human B cells mAT10971 Human B cells mAT10973 Human B cells mAT10974 Human B cells mAT10975 Human B cells mAT10976 Human B cells mAT10977 Human B cells mAT10978 Human B cells mAT10979 Human B cells mAT10980 Human B cells mAT10981 Human B cells

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mAT10982 Mouse B cells mAT10983 Mouse B cells mAT10984 Human B cells mAT10985 Human B cells mAT10986 Human B cells mAT10987 Human B cells mAT10988 Human B cells mAT10989 Human B cells mAT10990 Human B cells mAT10991 Human B cells mAT10992 Human B cells mAT10993 Human B cells mAT10994 Human B cells mAT10995 Human B cells mAT10996 hybridoma mAT10997 hybridoma mAT10998 hybridoma mAT10999 hybridoma mAT11000 hybridoma mAT11001 hybridoma mAT11002 hybridoma mATPH hybridoma mAT10914 Mouse B cells mAT11004 hybridoma mAT11005 hybridoma mATPOB hybridoma mAT11007 hybridoma mAT11008 hybridoma mAT11009 hybridoma matPOYU hybridoma mat! 1011 hybridoma

Example 3. Study of hybridoma supernatants using solid-phase binding ELISA.

Solid-phase binding ELISA was performed to detect supernatants with antibodies binding to the receptor binding domain (RBD) of the SARS-CoV-2-Spike protein. A protein consisting of the SARS-CoV-2 RBD (amino acids 319-541), expressed using a bX-histidine marker and two tyc epitope markers at the C-terminus (SARS-CoV-2-S-RBD-mmH; see also no. accession NCBI MN908947.3), applied at a concentration of 1 μg/ml to a 96-well plate in PBS buffer overnight at 4°C. Nonspecific binding sites were then blocked using 0.5% (w/v) BSA in PBS. Antibody supernatants or pure medium were diluted 1:40 or 1:50 with blocking buffer PSA + 0.5% BSA and transferred to washed microtiter plates. After incubation for one hour at room temperature, the wells were washed and the supernatant bound to the plate was detected using goat anti-human IgG conjugated to horseradish peroxidase (HRP) (Jackson Immunoresearch) or anti-mouse IgG conjugated to horseradish peroxidase (HRP). ) (Jackson Immunoresearch). The plates were then developed using TMB substrate solution (BD Biosciences) according to the manufacturer's recommendations and absorbance measured at 450 nm on a Victor X5 plate reader.

The ability of anti-SARS-CoV-2-S antibodies to bind the SARS-CoV-2S receptor binding domain (SARS-CoV-2-S-RBD) was assessed as described above using a SARS-CoV-2-S-protein binding ELISA. RBD-mmH applied to a microplate. Single-point binding of antibody supernatant to SARS-COV-2-S-RBD-mmH coated on 96-well microtiter plates was detected using anti-hFc or anti-mFc antibody conjugated to HRP.

Summary results of the binding analysis for the three studies are shown in Table 1. 4. SARS-CoV-2 binding signals (absorbance 450 nm) are indicated, with the pure background signal being presented as a negative reference for each experiment. A sample labeled IC (Indeterminate) exhibited an experimental plate abnormality and is therefore listed without a value. As shown in comparison with the control (clean medium), the analyzed supernatants showed a significant degree of binding to SARS-CoV-2-S-RBD.

Table 4

Binding of supernatants to the receptor-binding domain of the SARS-CoV-2 spike protein

Supernatant Supernatant dilution Detection antibody Binding signal (absorbance at 450 nm) mAT10913 1:50 a-hFc 2,752 mAT10914 1:50 a-hFc 2.857 mAT10915 1:50 a-hFc 2.76 mAT10932 1:50 a-hFc 2,718 mAT10933 1:50 a-hFc 2,762 mAT10934 1:50 a-hFc 2,688 mAT10935 1:50 a-hFc 2,676 mAT10936 1:50 a-hFc 2,644 mAT10937 1:50 a-hFc 2,664 mAT10920 1:50 a-hFc 2,683 mAT10921 1:50 a-hFc 2.633 mAT10922 1:50 a-hFc 2,595 mAT10923 1:50 a-hFc 2,353 mAT10924 1:50 a-hFc 2,269 mAT10930 1:50 a-hFc 2,451 mAT10938 1:50 a-hFc 2,536 mAT10939 1:50 a-hFc 2,516 mAT10940 1:50 a-hFc 2.77 mAT10941 1:50 a-hFc IC mAT10982 1:50 a-hFc 2.537 mAT10984 1:50 a-hFc 0.716 mAT10985 1:50 a-hFc 2.35 mAT10986 1:50 a-hFc 2.331 mAT10987 1:50 a-hFc 2.438 mAT10988 1:50 a-hFc 3,062 mAT10989 1:50 a-hFc 3.116 mAT10969 1:50 a-hFc 2.629 mAT10970 1:50 a-hFc 2,807 mAT10971 1:50 a-hFc 3,052 mAT10964 1:50 a-hFc 3,086 mAT10965 1:50 a-hFc 2,918 mAT10966 1:50 a-hFc 0.421 mAT10967 1:50 a-hFc 1.732 mAT10954 1:50 a-hFc 1,963 mAT10955 1:50 a-hFc 2,469 mAT10956 1:50 a-hFc 2.6 mAT10957 1:50 a-hFc 2.49 mAT10977 1:50 a-hFc 2.925 mAT11010 1:40 a-mFc 2,896 mAT11004 1:40 a-mFc 2,908 mAT11000 1:40 a-mFc 2.725 mAT11006 1:40 a-mFc 2,619 mAT11008 1:40 a-mFc 2,907 mAT10998 1:40 a-mFc 2.835 mAT10996 1:40 a-mFc 2.826 mAT11002 1:40 a-mFc 2,581 Wednesday only 1:50 a-hFc 0.069 Wednesday only 1:40 a-mFc 0.058 Wednesday only 1:50 a-hFc 0.055

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Example 4: Antibody binding to a virus-like particle expressing SARS-CoV-2-S.

To investigate the ability of a panel of anti-SARS-CoV-2-S monoclonal antibodies to bind the SARS-CoV-2 spike glycoprotein, we developed an in vitro binding assay using virus-like particles expressing the SARS-CoV-2 spike protein (VLP) on an electrochemiluminescence-based detection platform (MSD).

For transient expression of the SARS-CoV-2 spike protein (NCBI accession number MN908947.3, amino acids 16-1211; SEQ ID NO: 833), vesicular stomatitis virus (VSV) lacking glycoprotein G (VSV delta G) was pseudotyped for the spike protein SARS-CoV-2 (VSV-SARS-CoV-2-S) and was produced in HEK293T cells. As a negative control for VSV delta G binding, we pseudotyped VSV G protein (VSV-G).

Experiments were performed according to the following procedure. The two types of VLPs described above were diluted in PBS, seeded into 96-well carbon electrode plates (MULTI-ARRAY high-bind plate, MSD) and incubated overnight at 4°C to ensure VLP adhesion. Nonspecific binding sites were blocked with 2% (w/v) BSA in PBS for 1 h at room temperature (RT). Supernatants containing antibodies obtained from mice immunized with SARS CoV-2 or sera from infected humans, as well as controls containing blank medium diluted 1:10 or 1:20 in 1x PBS, were added to the plate-bound particles. +0.5% BSA buffer. The plates were then incubated for 1 h at room temperature with shaking and then washed with 1x PBS to remove unbound antibodies using an AquaMax2000 plate washer (MDS Analytical Technologies). Plate-bound antibodies were detected using SULFO-TAGTM-conjugated anti-human IgG (Jackson Immunoresearch) or SULFO-TAGTM-conjugated anti-mouse IgG (Jackson Immunoresearch) for 1 h at room temperature. After washing, the plates were developed using reading buffer (MSD) according to the procedure recommended by the manufacturer, and luminescence signals were recorded using a SECTOR Imager 600 (Meso Scale Development). Direct binding signals (in RLU) were recorded and the ratio of VLPs expressing SARS-CoV-2-S to nonspecific VLPs was calculated.

The ability of anti-SARS-CoV-2-S monoclonal antibodies to bind to VLPs expressing SARS-CoV-2-S compared to binding to nonspecific VLPs expressing VSV was assessed using an immunobinding assay as described above. Single point binding to immobilized VLPs on High Bind 96-well plates (MSD) was performed by diluting the antibody supernatant at 1:10 or 1:20, bound for 1 hour and detected using anti-human IgG or anti-mouse IgG conjugated with SULFO-TAGTM. Electrochemiluminescent binding signals were recorded on a Sector Imager 600 (MSD). RLU values were determined for antibody binding to VLPs. Ratios were calculated by comparing the binding signals of VLPs expressing SARS-CoV-2-S with control VLPs.

Summary results of the binding analysis for the three experiments are shown in Table 1. 5. The signal observed for VLPs expressing SARS-COV-2-S indicated binding, whereas comparison with negative VLPs provided relative background signal. Clean media samples provided basal secondary antibody binding signals to samples without supernatant. The specific binding values of the 46 antibodies were >4-fold higher than those for pure medium samples (20-35 RLU) using VLPs expressing SARS-CoV-2-S, with a range of binding signals of 85-13600 RLU. Ratios of VSVs expressing SARS-CoV-2-S : VSV-VLP (negative control) ranged from 1.1 to 22.7, with many having high background VSV-VLP signal. The mAb11002 ratio of 0.9 was likely due to the low concentration of monoclonal antibody in the supernatant sample.

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Table 5

SARS-CoV-2-S VLP binding

Supernatant Supernatant dilution Secondary detection antibody Linking signal VSVVLP (RLU) VSVSARSCoV-2-S VLP binding signal (RLU) Binding signal ratio: VSVSARS-CoV2-S/VSVVLP mAT10913 1:10 a-hFc 2155 3244 1.5 mAT10914 1:10 a-hFc 3885 5181 1.3 mAT10915 1:10 a-hFc 980 9022 9.2 mAT10932 1:10 a-hFc 989 10451 10.6 mAT 10933 1:10 a-hFc 507 966 1.9 mAT10934 1:10 a-hFc 3876 5041 1.3 mAT10935 1:10 a-hFc 2087 3867 1.9 mAT10936 1:10 a-hFc 2325 8076 3.5

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mAT10937 1:10 a-hFc 1404 1920 1.4 mAT10920 1:10 a-hFc 8366 10041 1.2 mAT10921 1:10 a-hFc 1194 5436 4.6 mAT10922 1:10 a-hFc 1473 2229 1.5 mAT10923 1:10 a-hFc 1224 1859 1.5 mAT10924 1:10 a-hFc 487 969 2 mAT 10930 1:10 a-hFc 1769 3207 1.8 mAT10938 1:10 a-hFc 1232 6623 5.4 mAT10939 1:10 a-hFc 1777 5074 2.9 mAT10940 1:10 a-hFc 606 2072 3.4 mAT10941 1:10 a-hFc 673 4588 6.8 mAT10982 1:10 a-hFc 1178 2016 1.7 mAT10984 1:10 a-hFc 2486 8989 3.6 mAT10985 1:10 a-hFc 2049 3279 1.6 mAT10986 1:10 a-hFc 2044 10831 5.3 mAT10987 1:10 a-hFc 1839 2450 1.3 mAT10988 1:10 a-hFc 1832 2305 1.3 mAT10989 1:10 a-hFc 672 1999 3 mAT10969 1:10 a-hFc 3096 3313 1.1 mAT10970 1:10 a-hFc 1364 5712 4.2 mAT10971 1:10 a-hFc 1135 7266 6.4 mAT10964 1:10 a-hFc 1439 8601 6

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mAT10965 1:10 a-hFc 743 1370 1.8 mAT10966 1:10 a-hFc 1428 6574 4.6 mAT10967 1:10 a-hFc 1446 9510 6.6 mAT10954 1:10 a-hFc 641 6308 9.8 mAT10955 1:10 a-hFc 932 1788 1.9 mAT10956 1:10 a-hFc 1030 1581 1.5 mAT10957 1:10 a-hFc 604 5544 9.2 mAT10977 1:10 a-hFc 4141 13600 3.3 MATIOYU 1:20 a-mFc 96 363 3.8 mAT11004 1:20 a-mFc 110 406 3.7 mATPOOO 1:20 a-mFc 333 592 1.8 mATIOOb 1:20 a-mFc 165 3747 22.7 mAT11008 1:20 a-mFc 103 324 3.1 mAT10998 1:20 a-mFc 74 218 2.9 mAT10996 1:20 a-mFc 51 85 1.7 mAT11002 1:20 a-mFc 156 146 0.9 Wednesday only 1:10 a-hFc thirty 35 1.2 Wednesday only 1:20 a-mFc 35 20 0.6 Wednesday only 1:10 a-hFc 39 29 0.7

Example 5. Neutralization by antibodies of the infectivity of the pseudovirus VSV-SARS-CoV-2-S.

To investigate the ability of a panel of anti-SARS-CoV-2-S monoclonal antibodies to neutralize SARS-CoV-2, an in vitro neutralization assay was developed using the VSV-SARS-CoV-2-S pseudovirus.

As described above, VSV pseudotype viruses were produced by transiently transfecting 293T cells with a plasmid encoding the SARS-CoV-2 spike protein. Cells were seeded in 15 cm plates at 1.2 x ^{10 7} cells per plate in complete DMEM one day before transfection of spike protein DNA at 15 μg/plate using 125 μl Lipofectamine LTX, 30 μl PLUS reagent and up to 3 ml Opti -Mem. 24 h after transfection, cells were washed with 10 ml PBS and then infected with VSV ^AGmNeon virus _at 0.1 MOI in 10 ml Opti-Mem. The virus was incubated with cells for 1 h, with gentle shaking every 10 min. Cells were washed 3 times with 10 ml PBS, then covered with 20 ml infection medium before incubation at 37°C, 5% CO ₂ for 24 hours. The supernatant was collected in 250 ml centrifuge tubes on ice, then centrifuged at 3000 rpm in for 5 min to sediment cell debris, aliquoted on ice, and then frozen at -80°C. Infectivity was tested on Vero cells before use in neutralization assays. This material was called VSV-SARS-CoV-2-S.

VSV-SARS-CoV-2-S neutralization assay.

On day 1, Vero cells were seeded at 80% confluence in T225 flasks. For seeding, the medium was separated from the cells, the cells were washed with 20 ml of PBS (Gibco: 20012-043), 5 ml of TrypLE was added and incubated for ~5 min at 37°C until the cells separated. To inactivate trypsin, 5 ml of complete DMEM was added and pipetted to distribute the cells. To count resuspended cells, 20,000 Vero cells were seeded in 100 μl of prewarmed complete DMEM per well of a 96-well black polystyrene microplate (Corning: 3904).

On day 2, VSV-SARS-CoV-2-S was thawed on ice and diluted 1:1 with infection medium.

In a 96-well V-bottom plate, each supernatant was diluted in 60 μl of infection medium. For media samples (negative control), 60 μL of diluted conditioned media was added to the wells. 60 µl of diluted VSV-SARS-CoV-2-S was added to each

-56044746 well, except for control wells with medium. 60 μl of infection medium was added to these wells. The pseudoviruses were then incubated with the diluted supernatants for 30 min at room temperature. The medium was removed from the plates with Vero cells, 100 μl of supernatant/pseudovirus mixtures were transferred to the cells and the plate was incubated at 37°C, 5% CO ₂ for 24 hours. Final dilutions of the supernatant in a ratio of 1:4 and 1:20, and for some samples 1:100, was used to evaluate the neutralization of VSV-SARS-CoV-2-S pseudoviruses.

On day 3 after 24-h incubation, the supernatant was removed from the cell wells and replaced with 100 μl of PBS. The plates were then read on a SpectraMax i3 with a MiniMax imaging cytometer.

The ability of anti-SARS-CoV-2-S antibodies to neutralize pseudotyped VSV-based virus expressing SARS-CoV-2-S was assessed using a fluorescence focus neutralization assay. Below are summary binding results from the three assays. The neutralization efficiency of the antibody at each dilution is presented as a percentage compared to a control sample simulating the supernatant. All antibodies exhibited neutralizing ability, and antibodies exhibiting higher neutralization may have more effective neutralizing ability, especially for the set of antibodies assessed at the 1:100 dilution.

Table 6 VLP Neutralization

Supernatant Neutralization (1:4 dilution) Neutralization (dilution 1:20) Neutralization (dilution 1:100) mAT10913 99.5 95.5 69.1 mAT10914 94.2 74.8 43.6 mAT10915 96.7 74.2 29.6 mAT10932 99.8 94.6 68 mAT 10933 99.8 98.9 88.4 mAT10934 99.9 99.8 98.4 mAT10935 99.6 98.5 88.8 mAT10936 99.7 99.1 92.9 mAT10937 97.5 87.7 56.3 mAT10920 99.5 95.5 69.1 mAT10921 98.2 91.4 46.1 mAT10922 99.8 99.1 88.4 mAT10923 99.5 92.9 67.7 mAT10924 98.1 85.4 55.2 mAT 10930 99.1 91.1 59 mAT10938 98.1 83 54.2 mAT10939 98.6 90.5 64 mAT10940 97 89.9 66.4

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mAT10941 98.9 92.9 73.8 mAT10982 97.4 83.8 44.5 mAT10984 99.8 95.1 83.4 mAT10985 99.7 88.4 63.5 mAT10986 99.7 98 86 mAT10987 99.3 97.7 94.6 mAT10988 97.6 87.6 62.2 mAT10989 100 99.8 98.2 mAT10969 97.2 91 63.7 mAT10970 99.6 96.7 82.4 mAT10971 99.5 97 73.9 mAT10964 99.7 99.7 94.1 mAT10965 98.5 87.6 68.6 mAT10966 99.5 95.5 76.2 mAT10967 98.9 91.4 69.2 mAT10954 99.8 96 70.7 mAT10955 98.8 88.6 62.7 mAT10956 97.1 84.1 61.6 mAT10957 97.6 76.4 48 mAT10977 95.5 79 47.7 mAT11010 85 54 N/A mAT11004 77 40 N/A mATPOOO 98 82 n/a m At11006 91 54 n/a mAT11008 96 77 n/a mAT10998 88 59 n/a mAT10996 85 58 n/a mAT11002 35 -1 n/a

* N/A: not verified.

Example 6 Antibody Testing in a Surrogate Assay for Antibody-Dependent Cell-Mediated Toxicity.

The ability of antibodies targeting the SARS-CoV-2 spike protein to interact with FcyR3a, an Fc receptor expressed prominently on natural killer (NK) cells and inducing antibody-dependent cell-mediated cytotoxicity (ADCC), was measured using a surrogate reporter bioassay. cells and target cells associated with an-58044746 antibodies. This assay used Jurkat T cells modified to express a luciferase reporter gene under the control of the transcription factor NFAT (NFAT-Luc) together with the high-affinity human FcYR3a receptor allotype ¹⁷⁶ Val (Jurkat/NFAT-Luc/hFcYR3a ¹⁷⁶ Val). The target cells were recombinant Jurkat T cells expressing human CD20 (used as a positive control with a human IgG1 antibody targeting CD20) and full-length SARS-CoV-2 spike protein under the control of a doxycycline-inducible promoter. Reporter cells were incubated with target cells, and engagement of FcYR3a through the Fc domain of human IgG1 antibodies bound to target cells resulted in activation of the transcription factor NFAT in the reporter cells and stimulated luciferase expression, which was then measured by luminescence readout.

Jurkat T cells were modified to constitutively express full-length human CD20 (amino acids M1-P297, NCBI accession no. NP690605.1), the transactivator protein Tet3G (cloned using the Takara pEF1a-Tet3G vector, cat. no. 631167), and doxycycline-inducible full-length SARS-CoV-2 spike protein (amino acids M1-T1273, NCBI accession number YP_009724390.1). Recombinant cells expressing the Jurkat/Tet3G/hCD20/SARS-CoV2 spike protein were sorted for high spike protein expression and further maintained in growth medium RPMI+10% FBS without tetracycline+P/S/G+500 μg/ml G418+1 µg/ml puromycin + 250 µg/ml hygromycin.

Jurkat T cells were modified to stably express a nuclear factor of activated T cell (NFAT)-luciferase reporter construct along with the high-affinity human FcYR3a receptor allotype ¹⁷⁶ Val (amino acids M1-K254, NCBI accession number P08637 VAR_003960). Recombinant reporter cells were maintained in growth medium RPMI1640+10% FBS+P/S/G+0.5 μg/ml puromycin+500 μg/ml G418.

36 hours before the start of the surrogate ADCC assay, 5x105 target cells/ml were induced in RPMI cell culture medium+10% FBS without tetracycline+P/S/G containing 1 μg/ml doxycycline (Sigma). The day before the experiment, reporter cells were separated to a density of 7.5x105 cells/ml in growth medium RPMI 1640 + 10% FBS + P/S/G + 0.5 μg/ml puromycin + 500 μg/ml G418.

Briefly, on the day of the experiment, target cells and reporter cells were transferred to assay medium (RPMI+10% FBS without tetracycline+P/S/G) and added in a 3:2 ratio (3x104 target cells/well and 2x104 reporter cells/well) into 384-well white microtiter plates followed by the addition of anti-SARS-CoV-2-S antibody supernatant at various concentrations. A positive control sample (CD20 antibody with human IgG1) and a negative control sample containing no antibody were included in each plate to normalize the detected ADCC activity of the anti-SARS-CoV-2-S antibody supernatants. The plates were incubated at 37°C/5% CO ₂ for 5 hours followed by the addition of an equal volume of ONE-Glo™ reagent (Promega) to lyse cells and detect luciferase activity. Light emission was recorded in relative light units (RLU) on an Envision multi-channel tablet reader (PerkinElmer), and the data were analyzed and normalized using the following equation:

ADCC activity (%) = 100 x (mean RLU (experimental samples) - mean RLU (background)) (mean RLU (positive control) - mean RLU (background)).

The ability of anti-SARS-COV-2-S antibodies to activate FcYR3a receptors was assessed in an ADCC surrogate assay using Jurkat/NFAT-Luc/FcYR3a ¹⁷⁶ Val) as reporter cells and Jurkat/hCD20/SARS-CoV2 Spike as target cells. Each antibody analyzed contained an IgG1 domain.

In table Figure 7 shows summary results showing the raw luciferase activity values and the calculated % of the positive control. A range of % ADCC activity was observed indicating activation of FcYR3a by antibodies in the supernatants. All samples demonstrated some degree of ADCC surrogate activity, and 10 antibody supernatants demonstrated ADCC surrogate activity superior to that observed for the positive control.

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Table 7

Surrogate ADCC activity of anti-SARS-CoV-2-S antibody supernatants

mat Average RLU ADCC ADCC (Activity (%) mAT10913 11480 111.9 mAT10914 21960 265.8 mAT10915 14280 153 mAT10932 13020 108.8 mAT 10933 9740 68.5 mAT10934 11680 92 mAT10935 11540 90.4 mAT10936 15160 133.8 mAT10937 12340 100.1 mAT10920 15480 137.8 mAT10921 10080 67.7 mAT10922 9140 56.3 mAT10923 13340 107.1 mAT10924 7220 33 mAT 10930 8900 53.4 mAT10938 12960 102.5 mAT10939 9440 59.7 mAT10940 12520 106.2 mAT10941 10340 77.2

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mAT10982 7900 59.4 mAT10984 6780 6.8 mAT10985 5840 2.8 mAT10986 6200 4.4 mAT10987 12020 29.4 mAT10988 7200 8.7 mAT10989 10200 21.5 mAT10969 10500 23.1 mAT10970 7640 10.6 mAT10971 7480 10 mAT10964 6380 5.1 mAT10965 6780 6.9 mAT10966 7080 10.4 mAT10967 6740 8.6 mAT10954 6940 9.8 mAT10955 6740 8.7 mAT10956 6760 8.8 mAT10957 7120 10.8 mAT10977 12980 33.8

Example 7. Analysis of the binding specificity of antibodies against SARS-CoV-2-S.

A Luminex binding assay was performed to determine the binding of anti-SARS-COV-2S antibodies to a panel of antigens. For this assay, antigens were immobilized by amine coupling or streptavidin capture into Luminex microspheres as follows: approximately 10 million MagPlex microspheres (Luminex Corp., MagPlex Microspheres, cat. no. MC10000 and MC12000) were resuspended by vortexing in 500 μl of 0.1 M NaPO4 , pH 6.2 (activation buffer) and then centrifuged to remove the supernatant. The microspheres were protected from light because they are photosensitive. The microspheres were resuspended in 160 μl of activation buffer and activated the carboxylate groups (-COOH) by adding 20 μl of 50 mg/ml N-hydroxysuccinimide (NHS, Thermo Scientific, catalog no. 24525) followed by the addition of 20 μl of 50 mg/ml 1-ethyl- 3-[3dimethylaminopropyl]carbodiimide (EDC, ThermoScientific, catalog no. 22980) at 25°C. After 10 min, the pH of the reaction was reduced to 5.0 by adding 600 μl of 50 mM MES, pH 5 (binding buffer), and the microspheres were vortexed and centrifuged to remove the supernatant. Activated microspheres were immediately mixed with 500 μl of 25 μg/ml protein antigen or streptavidin in binding buffer and incubated for 2 h at 25°C. The binding reaction was stopped by adding 50 μl of 1 M Tris-HCl, pH 8.0, the microspheres were vortexed, centrifuged and washed three times with 800 μl of PBS 0.005% (Tween20 0.05%) to remove unbound proteins and other reaction components. Microspheres were resuspended in 1 ml PBS, 2% BSA, 0.05% sodium azide at a rate of 10 million microspheres/ml. To capture antigens with streptavidin, 500 μl of 12.5 μg/ml biotinylated protein in PBS was added to streptavidin-coupled microspheres and incubated for one hour at 25°C. Microspheres were vortexed, centrifuged, and washed three times with 800 μl PBS and then blocked using 500 μl 30 mM biotin (Millipore-Sigma, catalog no. B4501) in 0.15 M Tris, pH 8.0. Microspheres were incubated for 30 min, then vortexed, centrifuged, and washed three times with 800 μl PBS. Microspheres were resuspended in 1 ml PBS, 2% BSA, 0.05% sodium azide at a rate of 10 million microspheres/ml.

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Microspheres for various proteins and biotinylated proteins were mixed at a rate of 2700 beads/ml, and 75 μl of microspheres were added to a well of a 96-well ProcartaPlex flat bottom plate (ThermoFisher, catalog no. EPX-44444-000) and mixed with 25 μl of the individual supernatants, containing antibodies against SARS-CoV-2. Samples and microspheres were incubated for 2 h at 25°C and then washed twice with 200 μl DPBS with 0.05% Tween 20. To determine antibody levels associated with individual microspheres, 100 μl of 2.5 μg/ml F(ab ') ₂ goat anti-human kappa chains conjugated to R-phycoerythrin (Southern Biotech, catalog no. 2063-09) in blocking buffer (for mouse Fc antibodies) or 100 µl 1.25 µg/ml AffiniPure F( ab') ₂ fragments of goat anti-mouse IgG with R-phycoerythrin specific for F(ab') ₂ fragment (Jackson Immunoresearch, catalog no. 115-116-072) in blocking buffer (for antibodies with Fc regions human) and incubated for 30 min at 25°C. After 30 min, samples were washed twice with 200 μL wash buffer and resuspended in 150 μL wash buffer. The plates were read on Luminex FlexMap 3D® (Luminex Corp.) and Luminex xPonent® software version 4.3 (Luminex Corp.). The SARS-CoV-2 proteins used in the analysis were:

RBD_(R319-F541).mmh: SEQ ID NO: 829,

RBD_(R319-F541).mFc: SEQ ID NO: 830,

RBD_(R319-F541).hFc: SEQ ID NO: 831.

Luminex binding results are shown in Table. 8 and 9 as the median fluorescence intensity (MFI) signal. The results show that 46 anti-SARS-CoV-2-S antibody supernatants specifically bound to SARS-CoV-2-S RBD proteins. These results also show that five of these antibodies cross-reacted with the RBD of the SARS coronavirus spike protein, with a binding signal greater than 1000 MFI.

Table 8

Signal of binding (MFI) of SARS-CoV-2 Spike RBD, SARS-CoV-2 Spike S1, SARS RBD, SARS Spike S1, MERS Spike and MERS RBD proteins with monoclonal antibodies against SARS-CoV-2 (with hFc) SARS-CoV2

Supernata nt SARS-CoV2 spike protein (RBD) (R319F541).mmH SARSCoV-2 spike protein (RBD) (R319F541).mm Η BtSARS-CoV2 spike protein (RBD)(R31 9F541).mFc SARS-CoV2 spike protein (RBD)(R31 9F541).mFc BtSARS-CoV2 spike protein (RBD)(R31 9-F541).hFc SARS-CoV2 spike protein (RBD)(R31 9-F541).hFc SARSCoV-2 Spike (RBD, Fcmarker) (Sino 40592- V05H) SARS-CoV2 spike protein (SI subunit, Fc marker) (Sino 40591V02H) SARS-CoV2 spike protein (SI subunit, Fc marker) (Sino 40591V08H) mAT10913 30709 29247 16645 33023 27452 31929 31561 18899 24931 mAT10914 31967 29650 15986 30740 25957 30464 30591 14914 21609 mAT10915 31795 30293 20062 31772 30625 32437 31267 17595 22917 mAT10932 29984 30133 17697 30640 26220 30559 29880 17627 22099 mAT 10933 33356 32090 19383 34944 30110 35106 34484 21178 27509 mAT10934 33797 32649 21238 34325 33016 35841 33636 20643 27483 mAT10935 34853 32603 19328 35886 31444 35611 35037 19991 25554 mAT10936 33947 32305 21636 33740 32810 33912 33613 19487 25187 mAT10937 33866 32225 19689 34233 31501 34624 33878 19553 26404 mAT10920 34842 34440 20254 36415 31708 36828 36277 21085 28516 mAT10921 24977 23596 11307 19429 18186 22306 21766 8959 12212 mAT10922 31768 30755 18629 32355 27854 33609 31376 18287 24678 mAT10923 35208 34289 19593 37372 33555 37756 36324 22502 28855 mAT10924 29730 27987 17044 28308 26898 28744 28423 15672 20577 mAT 10930 25119 25131 16563 28560 25922 28870 28744 16530 21151 mAT10938 29409 27069 17205 30533 24638 29593 29134 15431 21163 mAT10939 32196 30883 18746 33900 28857 32864 32472 18171 23928 mAT10940 35221 35290 21000 35978 30675 36507 34945 21350 25807 mAT!0941 32392 31171 20428 34061 28431 33347 33232 19668 26738 mAT10982 24263 22180 12278 23296 19935 23020 23066 10847 14017

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mAT10984 27854 26197 17054 28350 22479 28442 27808 15590 19245 mAT10985 30214 27854 15488 29443 24827 31054 28936 16219 20787 mAT10986 27187 25196 15921 28407 23388 27693 27693 16034 19061 mAT10987 32171 29074 16736 33115 26059 32757 31238 17465 23089 mAT10988 23858 22160 12659 26095 21793 24822 23949 12910 16208 mAT10989 17687 17286 11189 19568 16117 22435 19316 12263 14234 mAT10969 29550 27587 15391 31386 26565 31042 30950 18466 23959 mAT10970 33154 31662 20184 34739 29182 34991 34704 21047 24625 mAT10971 29355 28850 16660 28746 24602 30032 29848 16986 21579 mAT10964 31754 28907 19225 32420 27736 33074 32317 18650 24154 mAT10965 30812 26863 13707 27139 23351 29618 28034 14133 18864 mAT10966 30939 27440 17905 30363 25115 30778 29869 16403 23308 mAT10967 28453 26496 16771 29650 24263 28660 28061 15776 21869 mAT10954 30410 28281 18394 31284 24677 31768 29604 16626 21270 mAT10955 29627 28476 16785 30790 24689 31227 31054 17858 22675 mAT10956 27900 25690 12891 28349 24505 30225 28810 15013 19981 mAT10957 23411 20615 10566 18692 16725 22560 20258 8451 11989 mAT10977 16770 14605 8845 13827 12774 15216 16783 6476 9406

SARS MER S Supernata nt Human SARS coronavirus spike protein (receptor-binding domain), rabbit Fc (Sino 40150UZ 1B2) Human SARS coronavirus spike protein (receptor binding domain, His marker) (Sino 40150V08B2) Human SARS coronavirus virus spike subunit S1 protein Hismarker) (Sino 40150V08B1) Spipo protein in MERS-CoV (SAR SCoV- 2) (ECD, AK 11297, Hismark p) (Sino 40069 V08B) Spipo protein MERS-CoV (SAR SCoV2) S2 (AK 7261296, Hismark p) (Sino 40070 V08B) Spipo protein in MERS-CoV (SAR SCoV2) SI (AK 1-725, Hismark P) (Sino, 40069 V08H) MERSCoV spike protein fragment (NCoV/hob 1 coronavirus) (RBD, AK 367606, His marker) (Sino 40071- V08B1) MERSCoV spike protein SI protein (NCoV/hob 1 coronavirus) (AK 1725, His marker) (Sino 40069V08B1) MERS.m Fc (mAt266 3-L1) MERS.h Fc (mAt266 4-L1) BtMERS.h Fc (mAt266 4-L2) mAT10913 35 39 21 20 26 14 34 26 29 28 29 mAT10914 47 39 22 19 28 15 31 23 86 71 49 mAT10915 42 40 21 18 23 15 31 24 86 91 56 mAT10932 34 26 19 14 19 12 26 19 60 49 40 mAT10933 39 31 18 14 19 14 24 17 22 21 26 mAT10934 38 27 18 15 18 10 24 20 77 68 47 mAT10935 37 25 21 15 18 14 25 17 74 67 42 mAT10936 46 36 20 19 21 13 29 20 32 26 32 mAT10937 44 50 21 19 26 14 27 22 21 23 29 mAT10920 59 68 26 24 thirty 13 39 27 38 35 44 mAT10921 35 31 19 19 19 12 23 18 55 44 39 mAT10922 36 41 18 19 18 9 29 22 20 21 24 mAT 10923 53 66 29 23 36 14 37 25 24 29 39 mAT 10924 41 thirty 18 17 19 12 29 22 19 22 28 mAT 10930 42 49 19 16 20 14 27 22 29 24 29 mAT10938 38 36 19 16 19 13 25 20 86 65 46 mAT10939 38 50 19 16 18 14 27 19 41 27 thirty mAT 10940 32 28 20 15 18 eleven 22 19 18 21 25 mAT 10941 45 37 22 19 22 15 thirty 24 82 69 47 mAT 10982 thirty 54 24 17 21 13 29 20 64 60 42 mAT 10984 33 31 22 21 25 13 29 20 237 341 172 mAT10985 31537 32343 22721 18 28 14 31 22 168 195 159 mAT 10986 39 38 21 15 19 14 27 20 233 286 184 mAT 10987 33 27 22 15 23 15 28 23 196 235 172 mAT10988 41 67 25 17 29 14 32 25 169 181 130 mAT 10989 47 73 21 16 22 eleven 24 19 161 206 186 mAT 10969 37 34 20 16 20 eleven 26 19 21 22 29 mAT 10970 38 25 19 14 16 15 23 17 35 23 28 mAT 10971 32 31 20 15 13 13 20 19 44 29 24 mAT 10964 19999 23855 5186 15 17 13 20 19 19 22 26 mAT 10965 thirty 23 16 19 20 12 26 23 58 53 43 mAT 10966 35 21 20 16 16 12 24 16 56 53 42 mAT 10967 35 thirty 21 17 19 13 23 21 61 71 45 mAT 10954 thirty 26 15 17 16 10 18 21 57 61 41 mAT10955 36 21 14 15 18 16 20 19 57 48 42 mAT10956 32 24 16 15 16 13 22 24 58 49 41 mAT10957 32 22 16 15 18 eleven 22 19 40 29 28 mAT 10977 36 28 23 17 19 13 24 21 17 20 25

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Signal binding (MFI) proteins RBD SARS-CoV-2, Spike S1 SARS-CoV-2, RBD SARS, Spike S1 SARS

SPIKE MERS and RBD MERS with monoclonal antibodies against SARS-CoV-2-S (with mFc)

Table 9

SARS-CoV-2

Protein Protein BtSARS-CoV2 spike protein (RBD)(R31 9F541).mFc (mAt10621L2) SARS-CoV2 spike protein (RBD)(R31 9F541).mFc (mAt10621Ll) Protein Protein Supernata nt SARSCoV-2 spikes (RBD) (R319F541).mm Η (mAT1062 0-L1) SARSCoV-2 spikes (RBD) (R319F541).mm H (mAt1062 0-L2) BtSARS-CoV2 spike protein (RBD)(R31 9-F541).hFc (mAt10622L2) SARS-CoV2 spike protein (RBD)(R31 9-F541).hFc (mAt10622Ll) SARSCoV-2 Spike (RBD, Fcmarker) (Sino 40592V05H) SARS-CoV2 (2019nCoV) spikes (SI subunit, Fc marker) (Sino 40591V02H) SARS-CoV2 (2019nCoV) spikes (SI subunit, Fc marker) (Sino 40591V08H) t mAT11010 11024 12885 9349 14432 15688 8880 9628 5136 10794 mAT11004 3350 11337 4299 4583 7625 4877 6905 4482 9526 m At 11000 17802 10971 11335 23007 11593 22316 5671 9356 5415 mATPOB 5134 4744 1396 2866 3812 3985 3749 2052 1037 mAT11008 4047 3178 3047 4260 4106 2570 2311 6880 1419 mAT10998 1847 3837 2228 2230 467 1740 2005 724 717 mAT10996 9142 2906 4319 8738 5398 2084 16101 1425 6232 mAT11002 11558 10181 2197 9530 5471 9382 8461 1107 2867

SARS MERS Protein Protein Protein Protein Protein Fragment Protein S1 Protein squirrel thorns thorns thorns squirrel Supernate ant human SARS coronavirus spikes (receptor-binding SHY domain), rabbit Fc (Sino 40150UZ 1B2) human SARS coronavirus (receptor-binding domain, His marker) (Sino 40150V08B2) S1 subunits of spines human SARS coronavirus coronavirus Hismarker) (Sino 40150V08B1) MERSCoV (NCoV/Ho new coronavirus) (ECD, AK 11297, Hismarker) (Sino 40069V08B) MERSCoV (NCoV/Ho new coronavirus) S2 (AK 726-1296, Hismarker) (Sino 40070V08B) thorns MERSCoV (NCoV/Ho new coronavirus) S1 (AK 1-725, Hismarker) (Sino 40070V08H) thorns MERSCoV (NCoV/ho new coronavirus) (RBD, AK 367606, Hismarker) (Sino 40071- V08B1) spikes MERSCoV (NCoV/hovy coronavirus) (AK 1725, Hismarker) (Sino 40069V08B1) MER S mFc (mAb 2663 -L1) ME R.h Fc (mA 266 4- Ll) BtMERS. hFc (mAb 2664- L2) mAT11010 18276 16793 7421 7 14 14 19 18 134 28 28 mAT11004 5524 740 33 15 20 12 26 17 228 24 25 mAtI 1000 39 31 18 13 19 9 27 17 384 82 49 mATPOB 615 667 339 18 17 13 15 18 156 16 24 mAT11008 120 174 31 18 16 15 20 18 45 19 32 mAt10998 29 37 16 19 18 14 24 19 48 29 32 mAt10996 1355 1279 28 13 21 14 26 18 185 132 95 mAt11002 80 56 31 10 22 13 25 18 288 52 32

Example 8. Analysis of antibody diversity against SARS-CoV-2-S.

Binding assay was performed to determine the binding profile of anti-SARS-COV-2S antibodies. For this assay, antigens were immobilized by amine coupling as described above for the Luminex binding assay. Briefly, approximately 9 million MagPlex microspheres for 16 different bead areas (Luminex Corp., MagPLex Microspheres, MagPLex catalog no. MC10000 and MC12000) were resuspended by vortexing in 500 μl of 0.1 M NaPO4, pH 6.2, and then centrifuged to remove the supernatant. The microspheres were resuspended in 160 μl of activation buffer and activated the carboxylate groups (-COOH) by adding 20 μl of 50 mg/ml N-hydroxysuccinimide (NHS, Thermo Scientific, catalog no. 24525), followed by the addition of 20 μl of 50 mg/ml 1-ethyl -3-[3 dimethylaminopropyl]carbodiimide (EDC, ThermoScientific, catalog no. 22980) at 25°C. After 10 min, the pH of the reaction was reduced to 5.0 by adding 600 μl of 50 mM MES, pH 5 (binding buffer), and the microspheres were vortexed and centrifuged to remove the supernatant. Activated microspheres were immediately mixed with 500 μL of 20 μg/mL SARS-CoV-2 spike protein (RBD)(R319-F541)-mmH in binding buffers and incubated for 2 h at 25°C. The binding reaction was stopped by adding 50 μl of 1 M Tris-HCl, pH 8.0, the microspheres were vortexed, centrifuged and washed three times with 1000 μl of PBS. Microspheres were resuspended in 250 μl PBS at 9 million microspheres/ml.

of 16 regions of microspheres with protein attached by amine binding were modified for quantitative binding assay as follows: microspheres were washed twice with PBS with 5% DMSO, and 500 μl of the chemical or enzyme was dissolved according to the manufacturer's recommendations and added at a concentration of 10 nM into the amine-linked microspheres described above. The reaction mixture was then vortexed and incubated for 2 h at room temperature with rotation. Microspheres were washed 3 times with PBS containing 2% BSA. Microspheres were resuspended in 1 ml PBS at a concentration of 9 million microspheres/ml.

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Protein-modified and non-protein-modified (intact) microspheres were mixed at 2700 beads/ml, and plated at 75 µl microspheres per well of a 96-well ProcartaPlex flat-bottom plate (ThermoFisher, catalog no. EPX-44444-000) and mixed with 25 µl of individual supernatants containing antibodies against SARS-CoV-2-S. Samples and microspheres were incubated for 2 h at 25°C and then washed twice with 200 μl DPBS with 0.05% Tween 20. To determine antibody levels associated with individual microspheres, 100 μl of 2.5 μg/ml F(ab ') ₂ goat anti-human kappa chains conjugated to R-phycoerythrin (Southern Biotech, catalog no. 2063-09) in blocking buffer (for hFc antibodies) or 100 µl 1.25 µg/ml AffiniPure F(ab') ₂ fragments of goat anti-mouse IgG antibody with R-phycoerythrin, specific for F(ab') ₂ fragment (Jackson Immunoresearch, No.: 115-116-072) in blocking buffer (for antibodies with mFc) or 100 µl 1, 25 μg/ml anti-His marker antibody conjugated to R-phycoerythrin (Biolegend, catalog no. 362603) in blocking buffer (ACE-2 control, R&D, catalog no. 9333H) and incubated for 30 min at 25° C. After 30 min, samples were washed twice with 200 μL wash buffer and resuspended in 150 μL wash buffer. The plates were read on FlexMap 3D® (Luminex Corp.) and Luminex xPonent® software version 4.3 (Luminex Corp.).

The results of the quantitative Luminex binding assay are shown in Table. 10 as a median fluorescence intensity (MFI) signal. To define clusters, data were normalized to intact protein (unmodified microspheres) and grouped into clusters. 46 anti-SARSCoV-2 antibodies were classified into 9 clusters with 2 or more antibodies, and 11 antibodies were classified as individual nodes. Clusters were assigned based on the results of hierarchical clustering and dendrogram. These results show that the 46 anti-SARS-CoV-2-S antibody supernatants had different characteristics and binding profiles, suggesting that this collection of antibodies bound to different epitopes on the SARS-CoV-2 spike protein.

Table 10

Binding signal (MFI) and cluster affiliation of monoclonal antibodies against SARS-CoV-2-S to RBD.mmH SARS-CoV-2-S (unmodified and chemically or enzymatically modified)

Sample CLUSTER NONMODIFIED ANALYSIS SARS-CoV2 spike protein (RBD)(R319) F541).mmH MODI SARSCoV-2 spike protein (RBD)(R3 19F541).mm H SARSCoV-2 spike protein MOD2 (RBD)(R3 19F541).mm H MOD3 SARSCoV-2 spike protein (RBD)(R3 19F541).mm H MOD4 SARSCoV-2 spike protein (RBD)(R3 19F541).mm H MOD5 SARSCoV-2 spike protein (RBD)(R3 19F541).mm H MOD6 SARSCoV-2 spike protein (RBD)(R3 19- F541).mm H MOD7 SARSCoV-2 spike protein (RBD)(R3 19F541).mm H Human ACE2 (10 nM) 1 5727 873 5119 1852 5106 202 5408 5013 Human ACE2 (100 nM) 1 10681 1447 10320 2260 9661 559 9593 8624 Human ACE2 (50 nM) 1 9269 991 8238 2185 7707 391 7859 7577 mAT10969 3 28551 54 24177 425 26049 3546 20577 23878 mAT10965 3 28080 38 21996 135 25727 3250 22419 24062 mAT10913 4 31694 102 28389 23270 29344 5018 28738 27854 mAT10920 4 35534 162 26783 28090 32185 7105 32942 30958 mAT10923 4 38711 153 32305 33866 36082 7540 35335 33924 mAT 10930 4 29502 110 21579 21533 27843 6195 26600 25103 mAT10940 4 38871 94 34337 33453 36690 7817 36128 34544 mAT10989 4 19671 49 16697 18260 15785 3369 19568 15206 mATIOOb 4 2044 thirty 705 3773 2553 517 2024 2503 mAT10934 5 33057 81 27716 25092 31664 6648 30801 29926 mAT10924 5 39205 118 32707 29366 36507 6378 35565 34210 mAT10939 5 33647 62 24895 26392 31390 6276 31275 29594 mAT10988 5 23009 68 15983 14842 20830 3536 20176 19499 mAT10957 5 20879 52 15728 19383 19993 3582 17727 17989 mAT10914 6 36047 143 32282 26967 34199 7162 32787 31823

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mAT10915 6 36690 159 32489 26427 33545 9731 33568 31823 mAT10932 6 34024 191 28833 28557 31560 9946 31123 29765 mAT10938 6 34522 174 28465 19403 31252 8932 29225 30918 mAT10941 6 36369 140 31868 26129 33637 9455 33154 31478 mAT10984 6 25759 109 22445 20925 24747 6880 23630 23895 mAT10985 6 27394 99 24286 22986 26151 5519 25874 25023 mAT10986 6 25414 118 20868 20557 23619 6591 23066 22813 mAT10977 6 16980 54 14108 16590 15851 3505 14528 12779 mAT 10933 7 35267 69 30617 5243 32665 6161 32930 31043 mAT10982 7 27505 80 20338 6650 25051 4585 24178 23770 mAT10987 7 29327 54 25311 2235 27981 4110 27095 25690 mAT10935 8 31883 81 28683 12724 30329 6457 27417 27785 mAT10970 8 32271 94 26863 22547 30537 7029 27679 28333 mAT10971 8 27415 106 23890 22184 27850 6869 25337 25164 mAT10964 8 29963 122 23580 23419 27896 7085 27483 25968 mAT10921 9 31657 91 28216 18123 30441 6821 28629 28756 mAT10966 9 29489 85 22836 19866 25736 5869 24217 26013 mAT10967 9 26784 107 20787 13760 25104 6192 21329 23434 mAT10954 9 28476 74 21915 19038 26186 5948 25299 24332 mAT10955 9 28637 39 24585 21155 27912 4141 23849 24862 mAT10996 S1 3403 20 5275 164 5562 488 3042 9125 mAT10937 S2 33561 94 24890 104 31164 5904 30327 28675 mAT10936 S3 32919 136 26818 312 31261 7856 31008 29293 mAT10922 S4 33183 102 25384 1107 31348 5822 31313 29386 mAT11002 S5 9881 16 3348 155 8615 153 9542 7562 mAT10956 S6 24562 29 21685 19337 23769 2275 19422 21961 matPOYU S7 6388 18 4155 5441 8832 384 7444 5766 mAT11008 S8 7096 26 926 1525 2776 198 2750 1007 mAT10998 S9 2557 18 247 1336 1524 104 2937 723 mAT11004 S10 6514 18 2205 604 3566 1155 4522 2229 mATPOOO S11 16670 19 3416 12787 13493 2009 17756 12409 MOD8- MOD9- MOD10- MOD11- MOD12- MOD13- MOD14- MOD15- protein protein protein protein protein protein protein protein thorns thorns thorns thorns thorns thorns thorns thorns SARS- SARS- SARS- SARS- SARS- SARS- SARS- SARS- Sample CLUSTER CoV-2 CoV-2 CoV-2 CoV-2 CoV-2 CoV-2 CoV-2 CoV-2 (RBD)(R3 (RBD)(R3 (RBD)(R3 (RBD)(R3 (RBD)(R3 (RBD)(R3 (RBD)(R3 (RBD)(R3 19- 19- 19- 19- 19- 19- 19- 19- F541).mm F541).mm F541).mm F541).mm F541).mm F541).mm F541).mm F541).mm Η H H H H H H H Human ACE2 (10 nM) 1 36 4500 4091 4618 4505 5094 4743 3173 Human ACE2 (100 nM) 1 36 6212 7922 8440 8957 8948 7927 5370 Human ACE2 (50 nM) 1 35 5518 6447 7064 7233 7600 7112 4407 mAT10969 3 154 18918 24407 22409 27036 24269 23672 14196 mAT10965 3 110 19061 22355 21414 25635 23144 23156 14072 mAT10913 4 15939 28645 27110 28878 31159 28971 27784 26272 mAT10920 4 17228 32758 31463 31910 35144 32185 32323 29949 mAT10923 4 20961 34187 33809 36323 38596 35381 33338 33131 mAT 10930 4 10235 23744 24516 26738 27958 26968 25126 23951 mAT10940 4 14572 35967 34704 36070 39285 35462 34922 33614 mAT10989 4 6136 17756 15530 16838 15137 17411 18100 15946 mATPOB 4 299 2442 3749 1076 4622 2818 3344 3568 mAT10934 5 6410 31261 30364 30709 32873 30502 28591 27785 mAT10924 5 6594 32856 33797 35875 38424 34647 33476 31524 mAT10939 5 4808 28465 29444 30699 33475 30596 29721 27129 mAT10988 5 2980 18329 19660 20692 21770 20130 18948 16558 mAT10957 5 2171 17357 19487 18596 21247 18757 17810 16081 mAT10914 6 5475 31226 31467 33235 35175 32626 31100 29217 mAT10915 6 9277 33442 31984 32902 35462 31937 32397 30009 mAT10932 6 9711 30122 29074 30433 33379 30283 29880 26795

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mAT10938 6 7536 28109 30308 31264 33394 30814 30538 27751 mAT10941 6 7518 29802 31421 33958 35290 32925 31777 29159 mAT10984 6 3527 20212 22065 22318 26163 23227 22283 19349 mAT10985 6 6821 23642 23572 24654 27394 24677 24493 20787 mAT10986 6 2838 20672 21766 21720 25207 23400 22214 19694 mAT10977 6 4005 14193 12616 13320 16332 13632 14312 13136 mAT10933 7 1556 27705 29926 30801 34427 30409 30525 24367 mAT10982 7 1065 20361 23131 23247 26412 24027 23549 16765 mAT10987 7 1444 25621 25345 26335 29995 27049 26082 22871 mAT10935 8 2534 26151 27958 28752 30847 28522 27452 24816 mAT10970 8 1968 25233 27793 27610 31869 29871 26909 23775 mAT10971 8 1598 22587 25646 24384 27391 25761 24774 19590 mAT10964 8 2414 24740 25658 26439 29113 27243 26783 22405 mAT10921 9 941 23674 27586 27367 30969 28480 28331 21220 mAT10966 9 833 21800 24332 24977 27440 26554 24585 18580 mAT10967 9 574 19521 22352 22997 25506 22641 22836 17387 mAT10954 9 929 22237 24516 23457 28200 24897 24539 19717 mAT10955 9 1141 22191 24805 23688 27210 25575 24677 18944 mAT10996 S1 28 8940 6336 6789 6229 5821 3484 1312 mAT10937 S2 1231 27597 27092 29937 32116 29661 29386 20543 mAT10936 S3 2916 29074 28775 30813 31711 29189 28522 21674 mAT10922 S4 2248 29845 28629 30373 32931 30625 28962 23399 mAT11002 S5 17 4144 6415 6790 8465 7688 6804 2016 mAT10956 S6 331 16954 21282 21524 26646 21547 22767 15077 matPOYU S7 162 5567 6718 9557 12522 5287 5898 4915 mAT11008 S8 60 2350 2759 2824 3301 2745 2130 2831 mAT10998 S9 85 1611 2260 1206 2513 2186 727 1029 mAT11004 S10 71 1465 12665 10667 5925 5531 11578 1144 mATPOOO S11 56 14151 19230 17204 21718 17952 17117 5151

Example 9. Binding kinetics of monoclonal antibodies against SARS-CoV-2-S on Biacore.

Equilibrium dissociation constants (KD) of various SARS-CoV-2-S antibodies from primary supernatants of CHOt cells or from hybridomas were determined using a Biacore T200/Biacore 8K real-time surface plasmon resonance biosensor. All binding assays were performed in a running buffer of 10 mM HEPES, 150 mM NaCl, 3 mM EDTA, and 0.05% v/v. surfactant Tween-20, pH 7.4 (HBS-ET) at 25°C. The surface of the Biacore CM5 sensor chip was first modified by amine coupling with a mouse monoclonal anti-human Fc antibody or a rabbit monoclonal anti-mouse Fcy antibody (GE, catalog no. BR-1008-38) to capture antibodies against SARS-CoV-2. Binding studies were performed using the human SARS-CoV-2 extracellular RBD domain expressed with a C-terminal myc-myc-hexahistidine marker (SARS-COV-2 RBD-MMH), SARS-CoV-2 extracellular RBD domain expressed with a C-terminal IgG2a mouse (RBD-mFc SARS-CoV-2) or the extracellular domain of the RBD of SARS-CoV-2 expressed with the C-terminal human IgG1 (RBD-hFc SARS-CoV-2). Single concentrations of SARS-COV-2 RBD-MMH (100 nM); RBD-mFc SARS-CoV-2 (50 nM) or RBD-hFc SARS-CoV-2 (50 nM) in HBS-ET working buffer was injected for 1.5 min at a flow rate of 30 μl/min, dissociation of various RBD reagents Antibody-bound SARS-CoV-2 was monitored for 2 minutes in HBS-ET running buffer. At the end of each cycle, the anti-SARS-CoV-2 RBD capture surface was regenerated using a 10-second injection of 20 mM phosphoric acid for the mouse anti-human Fc monoclonal antibody surface or a 40-second injection of 10 mM glycine-HCl buffer, pH 1. 5, for a rabbit polyclonal anti-mouse Fcy antibody. Association rate constants (k _a ) and dissociation rate constants (k d ) were determined by fitting real-time binding sensorgrams to a mass transfer-limited 1:1 binding model using BiaEvaluation software version 3.1 or Biacore Insight Evaluation software version 2.0 or curve fitting software . The binding dissociation equilibrium constant (K _D ) and dissociation half-life (t1/ ₂ ) were calculated from the kinetic rates as:

^k d ( ^m ) = ^{and tl/2} ( ^min ) ⁼

The binding kinetics parameters for various anti-SARS-CoV-2 monoclonal antibodies binding to various SARS-COV-2 RBD reagents of the present invention at 25°C are shown in Table 1. 11 and 12.

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Table 11

Binding kinetics of SARS-COV-2 RBD-MMH to anti-SARS-CoV-2 monoclonal antibodies at 25°C

Supernatant mAb uptake level (EO) Binding of 50 nM Ag (EO) k _a (1/Ms) k _d (1/s) KD (M) (min) mAT10913 2010 381 4.91E+05 2.28E02 4.64E08 0.5 mAT10914 3169 174 3.49E+05 1.36E- 02 3.89E08 0.8 mAT10915 824 109 8.85E+04 3.18E- 04 3,ZOEOO 36.3 mAT10932 2261 326 8.50E+04 1.26E- 04 1.48E- 00 92 mAT 10933 1414 428 1.05E+06 4.08E03 3.88E00 2.8 mAT10934 2918 981 1.01E+06 4.3 5E03 4.32E00 2.7 mAT10935 3293 694 2D1E+05 3.99E03 1.89E- 08 2.9 mAT10936 2491 717 3.03E+05 8.81E- 04 2.91E00 13.1 mAT10937 1846 504 3.81E+05 5.73E03 1.50E- 08 2 mAT10920 1295 234 6.22E+05 2.20E02 3.54E08 0.5 mAT10921 1024 141 9.52E+04 4.99E04 5.24E09 23.1 mAT10922 2395 786 3.91E+05 2.00E03 5.11E- 09 5.8 mAT10923 1278 322 2.94E+05 6.04E03 2.06E08 1.9 mAT10924 766 166 1.97E+05 3.65E03 1.85E- 08 3.2 mAT10930 3137 328 8.90E+04 1.85E- 03 2.08E08 6.2 mAT10938 2167 180 6.60E+04 3.48E04 5.28E09 33.2 mAT10939 1505 241 1.69E+05 3.38E03 2.00E08 3.4 mAT10940 2149 698 3.34E+05 2.3 8E03 7.15E- 09 4.9

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mAT10941 1811 288 0.85E+04 5D7E- 04 5.25E09 22.3 mAT10982 1096 188 1.32E+05 2.71E- 03 2.06E08 4.3 mAT10984 1654 387 1.55E+05 3.70E04 2,ZOEOO 31.2 mAT10085 1974 749 0.41E+05 1.45E- 03 1.54E- 00 8 mAT10986 1560 524 3.21E+05 2.56E04 7.07E- 10 45.2 mAT10987 1242 356 4.50E+05 1.04E- 02 2.32E08 1.1 mAT10988 1227 291 1.27E+06 3.52E02 2.77E08 0.3 mAT10989 692 257 1.60E+06 ZD4E- 03 1.06E- 00 3.7 MATYOOO 2200 427 1.80E+05 4.71E- 03 2.61E- 08 2.5 mAT10970 1865 438 1.37E+05 7.00E04 5.82E00 14.4 mAT10971 1482 358 1.68E+05 4.40E04 2.67E00 25.8 mAT10964 1208 460 1.06E+06 7.56E04 7D4E- 10 15.3 mAT10065 1046 168 1D0E+05 2.73E03 2.28E08 4.2 mAT10966 1422 343 1.57E+05 4.40E04 2.81E- 00 26.3 mAT10967 1421 175 1D2E+05 1.08E- 04 0.66E- 10 106.0 mAT10054 1150 338 2.34E+05 4.05E04 1.73E- 00 28.5 mAT10955 1032 199 1.38E+05 2.60E03 1.05E- 08 4.3 mAT10056 1303 184 2.02E+05 5.31E- 03 2.62E08 2.2 mAT10057 736 163 1D4E+05 ZD5E- 04 2.35E00 36.7 mAT10977 221 57 2,ЗЗЭ+05 7D7E- 04 3.08E00 16D mat! 1010 1027 108 ZD5E+05 1.48E- 03 4.42E00 7.8 mAT11004 1111 161 1.88E+05 ZD2E- 03 1.66E- 08 3.7 m At11000 381 16 1.40E+05 2.41E- 02 1.72E- 07 0.5 m At11006 1118 49 8.07E+04 3.67E04 4D0E00 31.5 mAT11008 887 56 6.73E+04 4.00E03 5.04E08 2.0 mAT10998 1155 69 1.05E+05 2.28E02 1D7E- 07 0.5 MATYOOB 616 28 1.53E+05 1D0E- 02 7D8E- 08 1.1 mat! 1002 1070 8 3.21E+05 2.54E02 7.03E08 0.5

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Table 12

Kinetics of binding of RBD-mFc SARS-CoV-2 or RBD-hFc SARS-CoV-2 to monoclonal antibodies against SARS-CoV-2-S at 25°C

Supernatant mAb uptake level (EO) Binding of 50 nM Ag (EO) to _a k _d KD 1½ (1/Ms) (1/s) (Μ) (min) mAT10913 961 575 6.23E+05 1.52E- 04 2.44Ε- 10 76.1 mAT10914 1467 313 1.83E+05 1.00E05* 5.47Ε- eleven 1155* mAT10915 392 141 2.81E+05 1.00E05* 3.56Ε- eleven 1155* mAT10932 1060 372 2.42E+05 1.00E05* 4.1 WE- eleven 1155* mAT 10933 681 465 1.23E+06 2.12E- 04 1.73Ε- 10 54.4 mAT10934 1401 949 1.41E+06 1.17E- 04 8.32Ε- eleven 98.3 mAT10935 1667 830 3.83E+05 1.00E05* 2.61Ε- eleven 1155* mAT10936 1171 699 6.52E+05 1.00E- 05* 1.53Ε- eleven 1155* mAT10937 904 575 6.39E+05 7.28E05 1.14Ε- 10 158.7 mAT10920 617 357 7.02E+05 2.92E04 4.16Ε- 10 39.5 mAT10921 489 170 2.66E+05 1.00E- 05* 3.75Ε- eleven 1155*

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mAT10922 1286 828 7D9E+05 2.42E05 3.36Ε- eleven 478.2 mAT10923 613 362 6.51E+05 2.83E05 4.35Ε- eleven 407.7 mAT10924 465 223 3.67E+05 8, BEOS 2.22Ε- 10 142.1 mAT10930 2156 449 2.32E+05 Ι,ΟΟΕ- 05* 4.31Ε- eleven 1155* mAT10938 1363 333 ZD1E+05 Ι,ΟΟΕ- 05* 3.22Ε- eleven 1155* mAT10939 904 324 2.99E+05 1.15E- 05 3.87Ε- eleven 1004.3 mAT10940 1508 893 5.61E+05 2.86E05 5.09Ε- eleven 403.8 mAT10941 1132 371 2.60E+05 1.00E- 05* 2.1 SEII 1155* mAT10982 529 236 ZD0E+05 1.69E- 05 5.44Ε- eleven 683.6 mAT10984 1213 573 4.02E+05 1.00E- 05* 2.49Ε- eleven 1155* mAT10985 1463 1040 1.09E+06 1.27E- 05 1.17Ε- eleven 910.9 mAT10986 1168 752 6,ЗЗЭ+05 1.00E- 05* 1.58Ε- eleven 1155* mAT10987 902 632 8.20E+05 1.70E- 04 2.08Ε- 10 67.8 mAT10988 892 628 1.24E+06 3.46E04 2.79Ε- 10 33.4 mAT10989 505 378 2.07E+06 9.3 0E05 4.50Ε- eleven 124.2 mAT10969 1658 738 3.05E+05 1.51E- 05 4.96Ε- eleven 764 mAT10970 1370 661 3.48E+05 1.00E- 05* 2.88Ε- eleven 1155* mAT10971 1081 556 3.95E+05 Ι,ΟΟΕ- 05* 2.53Ε- eleven 1155* mAT10964 875 651 1.43E+06 Ι,ΟΟΕ- 05* 7.00Ε- 12 1155* mAT10965 762 322 2.97E+05 Ι,ΟΟΕ- 05* 3.36Ε- eleven 1155* mAT10966 921 430 4.02E+05 Ι,ΟΟΕ- 05* 2.49Ε- eleven 1155* mAT10967 945 355 3.99E+05 Ι,ΟΟΕ- 05* 2.51Ε- eleven 1155*

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mAT10954 734 414 5.77E+05 1.00E- 05* 1.73E- eleven 1155* mAT10955 634 292 3.96E+05 2.34E05 5.92E- eleven 493.6 mAT10956 842 339 3.74E+05 1.48E- 04 3.95E- 10 78 mAT10957 449 209 3.58E+05 1.00E- 05* 2.79E- eleven 1155* mAT10977 161 102 5.56E+05 1.04E- 04 1.87E- 10 110.9 matPOYU 1014 163 4.24E+05 1.00E- 05* 2.3 6E- eleven 1155* m At11004 1101 241 3.46E+05 6.63E05 1.91E- 10 174.2 m At11000 380 61 4.38E+05 1.83E- 03 4D7E- 09 6.3 mATPOB 1112 75 1.88E+05 1.00E- 05* 5.32E- eleven 1155* mAT11008 872 110 1.61E+05 1.15E- 04 7.15E- 10 100.4 mAT10998 1140 227 3.30E+05 5.21E- 04 1.58E- 09 22.2 mAT10996 629 83 2.88E+05 9.32E04 3.24E09 12.4 mat! 1002 1068 60 2.69E+05 4.49E03 1.67E- 08 2.6

*: Estimated value based on the measurement limit of the dissociation rate constant and dissociation half-life under experimental conditions.

Example 10. Study of monoclonal antibodies against SARS-CoV-2-S using solid-phase blocking ELISA.

An ELISA-based blocking assay was developed to determine the ability of anti-SARS-CoV2-S antibodies to block the binding of the SARSCoV-2 spike protein receptor binding domain (RBD) to human angiotheisin-converting enzyme 2 (hACE2).

The SARS-CoV-2 protein used in the experiments consisted of a fragment of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (amino acids Arg319 to Phe541) expressed with the C-coyce Fc fragment of human IgGl (RBD-hFc SARS- CoV-2; see NCBI accession number MN908947.3). The human ACE2 protein used in the experiments was purchased from R&D systems and consisted of the amino acids glutamine-18 to serine-740 with a C-coice 1 OX-histidium marker (hACE2-His; NCBI accession number Q9BYF1).

Experiments were performed according to the following procedure. Anti-penta-His monoclonal antibody (Qiagen) was applied to a 96-well microtiter plate at a concentration of 1 μg/ml in PBS overnight at 4°C. The hACE2-His receptor was added at a concentration of 0.2 μg/ml in PBS and bound for 2 h at room temperature. Nonspecific binding sites were then blocked using 0.5% (w/v) BSA in PBS. In other microtiter plates, a constant amount of 10 pM or 15 pM (as indicated in Table 13) of SARS-CoV-2 RBD-hFc protein was bound to antibodies diluted in PBS + 0.5% BSA in a ratio of 1:10 or 1: 20. These antibody-protein complexes, after an hour's incubation, were transferred to a microtiter plate with immobilized hACE2-His. After 1.5 h of incubation at room temperature, wells were washed and plate-bound SARS-CoV-2 RBD-hFc protein was detected using horseradish peroxidase (HRP)-conjugated goat anti-human IgG antibody (Jackson). The plates were then developed using TMB substrate solution (BD Biosciences, catalog no. 555214) according to the manufacturer's recommendations, and the absorbance was measured at 450 nm on a Victor X5 plate reader.

Data were analyzed by calculating the % signal reduction of a fixed concentration of SARS-CoV-2-S RBD-hFc in the presence of antibody compared to the absence of antibody. In the calculations, the binding signal of a sample with a constant level of SARS-CoV-2-S RBD-hFc without the presence of antibody for each plate was considered 100% binding or 0% blocking; the initial signal of a pure medium sample without SARS-CoV-2 RBD-hFc was considered as 0% binding or 100% blocking.

The ability of anti-SARS-CoV-2-S antibodies to block the binding of the SARS-CoV-2-S RBD to human ACE2 was assessed using a blocking ELISA format. Single-point blocking of binding of 10 pM or 15 pM SARS-CoV-2-S RBD-hFc to hACE2-His test antibody supernatant, illustrated by an anti-His marker antibody applied to 96-well

-72044746 microtiter plates, detected with anti-hFc antibody conjugated to

PH.

Summary blocking results for the three analyzes are shown in Table. 13. SARS-CoV-2-S binding signal (450 nm) and calculated % blocking are shown. A range of blocking values were observed for the experimental samples. For samples reporting N/A in columns 6 and 7, the plate-corrected value is included in columns 4 and 5 because the data are consistent with a single plate switch for these samples. 43 of 46 antibody supernatants blocked >50% of SARS-CoV-2-S RBD-hFc binding to human ACE2 immobilized on the plate, with 16 of these blocking >90% of the signal.

Table 13

Results of solid-phase ELISA blocking

Supernata nt Fixed different concentration of SARS-CoV2 RBD Dilution of the supernate The significance of the binding of SARSCoV-2 RBDhFc to ACE2, % blocking of SARSCoV-2 RBD-hFc with ACE2, Binding of SARSCoV-2 RBDhFc to ACE2, representing % blocking of SARSCoV-2 RBD-hFc with ACE2, mAT10913 15 pM 1:10 presented with a HIS marker, corrected for the tablet (absorbance at 450 nm) 0.206 presented with a HIS marker, corrected for the tablet (absorbance at 450 nm) 80.5 recorded with HIS marker m (abs. at 450 nm) 0.206 presented with HISmarker (abs. at 450 nm) 80.5 mAT10914 15 pM 1:10 0.326 59.1 0.326 59.1 mAT10915 15 pM 1:10 0.171 89.7 0.171 89.7 mAT10932 15 pM 1:10 0.254 57.3 0.254 57.3 mAT10933 15 pM 1:10 0.158 96.3 0.158 96.3 mAT10934 15 pM 1:10 0.209 78 0.209 78 mAT10935 15 pM 1.10 0.238 69.4 0.238 69.4 mAT10936 15 pM 1:10 0.234 70.6 0.234 70.6 mAT10937 15 pM 1:10 0.176 88.1 0.176 88.1 mAT10920 15 pM 1:10 0.601 -56.5 0.601 -56.5 mAT10921 15 pM 1:10 0.192 82.7 0.192 82.7 mAT10922 15 pM 1:10 0.181 86.4 0.181 86.4 mAT10923 15 pM 1:10 0.237 43.6 0.237 43.6 mAT10924 15 pM 1:10 0.175 78.2 0.175 78.2 mAT 10930 15 pM 1:10 0.241 42.5 0.241 42.5 mAT10938 15 pM 1:10 0.169 87.5 0.169 87.5 mAT10939 15 pM 1:10 0.204 65.6 0.204 65.6

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mAT10940 15 pM 1:10 0.152 95.2 0.152 95.2 mAT10941 15 pM 1:10 0.174 97.2 0.174 97.2 mAT10982 15 pM 1:10 0.195 83.5 0.195 83.5 mAT10984 15 pM 1:10 0.166 96.3 N/A N/A mAT10985 15 pM 1:10 0.162 97 n/a n/a mAT10986 15 pM 1:10 0.158 97.8 n/a n/a mAT10987 15 pM 1:10 0.243 81.8 n/a n/a mAT10988 15 pM 1:10 0.244 84 0.244 84 mAT10989 15 pM 1:10 0.155 101.8 0.155 101.8 mAT10969 15 pM 1:10 0.221 87.8 0.221 87.8 mAT10970 15 pM 1:10 0.164 97.7 0.164 97.7 mAT10971 15 pM 1:10 0.17 96.7 0.17 96.7 mAT10964 15 pM 1:10 0.169 96.9 0.169 96.9 mAT10965 15 pM 1:10 0.158 98.8 0.158 98.8 mAT10966 15 pM 1:10 0.157 94.2 0.157 94.2 mAT10967 15 pM 1:10 0.145 97.9 0.145 97.9 mAT10954 15 pM 1:10 0.147 97.3 0.147 97.3 mAT10955 15 pM 1:10 0.162 92.7 0.162 92.7 mAT10956 15 pM 1:10 0.189 84.5 0.189 84.5 mAT10957 15 pM 1:10 0.154 95.1 0.154 95.1 mAT10977 15 pM 1:10 0.315 71.5 0.315 71.5 mAT11010 10 pM 1:20 0.186 82.1 0.186 82.1 mAT11004 10 pM 1:20 0.211 70 0.211 70 m At11000 10 pM 1:20 0.173 72.7 0.173 72.7 m At11006 10 pM 1:20 0.236 58 0.236 58 mAT11008 10 pM 1:20 0.213 69.1 0.213 69.1 mAT10998 10 pM 1:20 0.185 61.6 0.185 61.6 mAT10996 10 pM 1:20 0.295 -18.1 0.295 -18.1 mAT11002 10 pM 1:20 0.177 79.2 0.177 79.2

Example 11: Epitope mapping of anti-SARS-CoV-2-S monoclonal antibodies on the spike glycoprotein using hydrogen-deuterium exchange mass spectrometry.

Hydrogen-deuterium exchange mass spectrometry (HDX-MS) was performed to determine the amino acid residues of the SARS-CoV-2 spike protein receptor binding domain (RBD (amino acids R319-F541)) interacting with mAb10989, mAb10987, mAb10934, mAb10933, mAb10920,

- 74 044746 mAT10922, mAT10936, mAT10954, mAT10964, mAT10977, mAT10984 and mAT10986. A general description of HDXMS is presented, for example, in Ehring (1999) Analytical Biochemistry 267(2):252-259; m Engen and Smith (2001) Anal. Chem. 73:256A-265A.

HDX-MS experiments were performed on a comprehensive HDX/MS platform consisting of a Leaptec HDX PAL system for deuterium labeling and reaction stopping, a Waters Acquity I-Class (two-component solvent system) for sample digestion and loading, a Waters Acquity IClass (system for working with two-component solvents) for an analytical gradient and a Thermo Q Exactive HF mass spectrometer for measuring the mass of peptides.

The labeling solution was prepared as PBS buffer in D2O at pD 7.0 (10 mM phosphate buffer, 140 mM NaCl and 3 mM KCl, equivalent to pH 7.4 at 25°C). For deuterium labeling, 10 μl of RBD protein or RBD protein premixed with each of the 12 antibodies listed above was incubated at 20°C with 90 μl of D2O labeling solution at different time points in duplicate. For mAb10989, mAb10987, mAb10934, and mAb10933, the time points were 0 min (nondeuterated control), 5 min, and 10 min. For mAb10920, mAb10922, mAb10936, mAb10954, mAb10964, mAb10977, mAb10984, and mAb10986, the time points were 0 min (non-deuterated control) and 10 min. The deuteration reaction was stopped by adding 90 μL of pre-cooled reaction stop buffer (0.5 M TCEP-HCl, 4 M urea, and 0.5% formic acid) to each sample for 90 seconds of incubation at 20°C. After stopping the reaction, samples were injected into the Leaptec HDX PAL system for real-time pepsin/protease XIII digestion. Digested peptides were captured with a C18 column (2.1 mm x 5 mm, Waters) and separated with another C18 column (2.1 mm x 50 mm, Waters) at -5°C with a 20-minute gradient (for mAb10989, mAb10987, mAb10934 and mAb10933) or 10-minute gradient (for mAb10920, mAb10922, mAb10936, mAb10954, mAb10956, mAb10964, mAb10977 and mAb10984) from 0% to 90% mobile phase solution B (mobile phase solution A: 0.5% formic acid and 4.5 % acetonitrile in water, mobile phase solution B: 0.5% formic acid in acetonitrile). The eluted peptides were analyzed by mass spectrometry on Q Exactive HF in LC-MS/MS or LC-MS mode.

LC-MS/MS data for a nondeuterated RBD protein sample were compared to a database including amino acid sequences of RBD protein, pepsin, protease XIII, and their reverse sequences using the Byonic search algorithm (Protein Metrics). Search parameters were set to default using nonspecific enzymatic digestion and glycosylation of human proteins as the common variable modification. The list of identified peptides was then imported into HDExaminer software (version 3.1) to calculate deuterium absorbance (D-absorbance) and deuterium percentage difference (Δ%D) values for all deuterated samples. The difference in the percentage of deuterium (Δ%D) was calculated as follows.

Deuterium absorbance difference (AD) = D-absorbance (RBD-mAb) - D-absorbance (RBD only) up to

Difference in percentage absorption of deuterium (Δ%ϋ) = ---------------------------------------- --------x 100

Theoretical maximum D - peptide uptake

For both RBD alone and RBD complexed with mAb10989 samples, a total of 190 RBD peptides were identified, representing 86.06% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., Δ%D value less than -5%, eg -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 467-513 (DISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVL) (SEQ ID NO: 835) RBD were significantly protected by mAb10989.

For both RBD alone and RBD complexed with mAb10987 samples, a total of 187 RBD peptides were identified, representing 86.06% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., Δ%D value less than 5%, eg -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 432-452 (CVIAWNSNLDSKVGGNYNYL) (SEQ ID NO: 836) RBD were significantly protected by mAb10987.

For both RBD alone and RBD complexed with mAb10934 samples, a total of 188 RBD peptides were identified, representing 86.06% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., Δ%D value less than -5%, eg -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 432-452 (CVIAWNSNNLDSKVGGNYNYL) (SEQ ID NO: 836), 467-474 (DISTEIYQ) (SEQ ID NO: 837) and 480-513 (CNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVL) (SEQ ID NO: 838) RBD were significantly protected s mAT10934.

For both RBD alone and RBD complexed with mAb10933 samples, a total of 188 RBD peptides were identified, representing 86.06% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., Δ%D value less than 5%, e.g., -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 467-510 (DISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRV) (SEQ ID NO: 839) of the RBD were significantly protected by mAb10933.

For both RBD alone and RBD complexed with mAb10920 samples, a total of 75 RBD peptides were identified, representing 83.27% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., A%D value less than -5%, e.g., -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 471-486 (EIYQAGSTPCNGVEGF) (SEQ ID NO: 840) and 491-515 (PLQSYGFQPTNGVGYQPYRVVVLSF) (SEQ ID NO: 841) of the RBD were significantly protected by mAb10920.

For both RBD alone and RBD complexed with mAb10922 samples, a total of 86 RBD peptides were identified, representing 87.25% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., A%D value less than -5%, e.g., -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 432-452 (CVIAWNSNLDSKVGGNYNYL) (SEQ ID NO: 836) RBD were significantly protected by mAb10922.

For both RBD alone and RBD complexed with mAb10936 samples, a total of 81 RBD peptides were identified, representing 82.07% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., A%D value less than -5%, e.g., -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 351-360 (YAWNRKRISN) (SEQ ID NO: 842), 432-452 (CVIAWNSNNLDSKVGGNYNYL) (SEQ ID NO: 836), 467-486 (DISTEIYQAGSTPCNGVEGF) (SEQ ID NO: 843) and 491-513 ( PLQSYGFQPTNGVGYQPYRVVVL) (SEQ ID NO: 844) RBD were significantly protected by mAb10936.

For both RBD alone and RBD complexed with mAb10954 samples, a total of 84 RBD peptides were identified, representing 87.25% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., A%D value less than -5%, e.g., -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 400-422 (FVIRGDEVRQIAPGQTGKIADYN) (SEQ ID NO: 845), 453486 (YRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGF) (SEQ ID NO: 846) and 490-515 (FPLQSYGFQPTNGVGYQPYRVVVLSF) (SEQ ID NO: 847) RBD were significantly protected by mAb10954.

For both RBD alone and RBD complexed with mAb10964 samples, a total of 109 RBD peptides were identified, representing 83.67% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., A%D value less than 5%, e.g., -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 401-424 (VIRGDEVRQIAPGQTGKIADYNYK) (SEQ ID NO: 848) and 471-513 (EIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVL) (SEQ ID NO: 849) RBD were significantly protected by mAb10964.

For both RBD alone and RBD complexed with mAb10977 samples, a total of 78 RBD peptides were identified, representing 87.25% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., A%D value less than -5%, e.g., -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 351-364 (YAWNRKRISNCVAD) (SEQ ID NO: 850) and 471-486 (EIYQAGSTPCNGVEGF) (SEQ ID NO: 840) of the RBD were significantly protected by mAb10977.

For both RBD alone and RBD complexed with mAb10984 samples, a total of 88 RBD peptides were identified, representing 87.25% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., A%D value less than -5%, e.g., -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 400-422 (FVIRGDEVRQIAPGQTGKIADYN) (SEQ ID NO: 845) and 453486 (YRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGF) (SEQ ID NO: 846) RBD were significantly protected by mAb10984.

For both RBD alone and RBD complexed with mAb10986 samples, a total of 84 RBD peptides were identified, representing 87.25% RBD sequence coverage. Any peptide that exhibited a 5% or greater reduction in deuterium uptake (i.e., A%D value less than -5%, e.g., -6%, -10%, etc.) upon mAb binding was determined to be significantly protected. Peptides corresponding to amino acids 400-422 (FVIRGDEVRQIAPGQTGKIADYN) (SEQ ID NO: 845), 453486 (YRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGF) (SEQ ID NO: 846) and 490-515 (FPLQSYGFQPTNGVGYQPYRVVVLSF) (SEQ ID NO: 847) RBD were significantly protected by mAb10986.

Overall, the majority of neutralizing antibodies analyzed bound to the RBD, overlapping RBD residues that constitute the region of interaction with ACE2; Additionally, antibodies can be grouped based on their contact pattern with the RBD surface, as shown in FIG. 15. The above summary data is also presented in table. 14-25.

- 76 044746

Table 14

Spike protein receptor binding domain (RBD) peptides with significant protection upon RBD-mAb complex formation compared to RBD alone

RBD Leftovers 5 min incubation 10 min incubation RBD- mAT10989 RBD RBD- mAT10989 RBD D- absorption D- absorption ΔΌ D- absorption Dabsorption ΔΌ Δ% D 467-474 2.67 3.16 0.49 2.53 3.17 0.64 -10.5 470-473 0.48 0.98 0.50 0.47 0.98 0.51 -28.0 470-474 0.99 1.46 0.47 0.99 1.44 0.45 -16.9 471-474 0.51 0.89 0.38 0.51 0.89 0.38 -20.9 475-486 2.20 2.93 0.73 2,I 2.94 0.83 -9.7 475-487 3.31 4.50 1.19 3.61 4.48 0.87 -11.4 475-489 2.77 4.48 1.71 2.78 4.53 1.75 -16.0 475-490 2.63 4.96 2.33 2.67 4.97 2.30 -19.8 480-489 1.82 3.67 1.85 1.77 3.69 1.92 -26.2 483-486 0.31 0.78 0.47 0.30 0.78 0.48 -26.5 487-489 0.05 0.40 0.35 0.02 0.39 0.37 -40.4 487-490 oh and 0.90 0.79 oh and 0.84 0.73 -42.3 487-491 0.10 1.05 0.95 0.10 1.03 0.93 -52.0 487-495 0.62 1.59 - 0.67 1.57 - -17.4 0.97 0.90 487-509 5.63 6.99 1.36 5.68 7.02 1.34 -8.3 487-510 6.08 7.37 1.29 6.08 7.44 1.36 -7.7 487-512 5.72 6.48 0.76 5.60 6.77 1.17 -5.1 487-513 5.15 6.16 1.01 5.07 6.14 1.07 -5.3 488-490 0.03 0.22 0.19 0.00 0.23 0.23 -23.2 488-491 0.04 0.37 0.33 0.04 0.36 0.32 -36.3

- 77 044746

Table 15

Spike protein RBD peptides with significant protection upon complex formation

RBD-mAt10987 compared to RBD itself

RBD Leftovers 5 min incubation 10 min incubation RBDmAt10987 RBD RBDmAt10987 RBD Dabsorption D- absorption ΔΌ D- absorption D- absorption ΔΌ Δ% D 432-441 1.62 2.17 0.55 1.64 2.18 0.54 -7.6 432-449 5.60 6.59 0.99 5.54 6.59 1.05 -7.1 432-452 6.20 7.49 1.29 6.20 7.46 1.26 -7.5 433-441 1.50 2.00 0.50 1.49 2.01 0.52 -8.1 440-452 3.95 4.81 0.86 4.03 4.80 0.77 -8.3 442-449 2.49 2.98 0.49 2.60 2.99 0.39 -8.2

- 78 044746

Table 16

RBD peptides with significant protection upon formation of the RBD-mAt10934 complex compared to RBD alone

5 minutes incubation 10 min incubation RBD RBD- mAT10934 RBD RBD- mAT10934 RBD Leftovers D- absorption D- absorption AD D- absorption Dabsorption AD A% D 432-452 5.70 7.49 1.79 5.62 7.46 1.84 -10.6 433-441 1.60 2.00 0.40 1.63 2.01 0.38 -6.2 434-441 2.24 2.42 0.18 2.13 2.52 0.39 -5.3 440-452 3.12 4.81 1.69 3.10 4.80 1.70 -17.1 442-449 2.37 2.98 0.61 2.37 2.99 0.62 -11.4 442-452 2.67 4.21 1.54 2.66 4.23 1.57 -19.1 443-452 2.53 3.78 1.25 2.52 3.78 1.26 -17.5 444-451 1.79 2.73 0.94 1.80 2.73 0.93 -17.2 444-452 1.82 3.09 1.27 1.75 3.09 1.34 -20.7 445-452 1.24 2.42 1.18 1.24 2.43 1.19 -22.0 467-474 2.64 3.16 0.52 2.58 3.17 0.59 -10.2 470-473 0.51 0.98 0.47 0.55 0.98 0.43 -25.0 470-474 1.03 1.46 0.43 1.01 1.44 0.43 -16.0 471-474 0.56 0.89 0.33 0.55 0.89 0.34 -18.6 480-489 3.19 3.67 0.48 3.19 3.69 0.50 -6.8 487-489 0.04 0.40 - 0.06 0.39 - -38.6

- 79 044746

487-490 0.54 0.90 0.36 0.36 0.53 0.84 0.33 0.31 -18.8 487-491 0.63 1.05 0.42 0.70 1.03 0.33 -20.5 487-495 0.73 1.59 0.86 0.71 1.57 0.86 -16.0 487-509 5.55 6.99 1.44 5.57 7.02 1.45 -8.9 487-510 5.89 7.37 1.48 6.00 7.44 1.44 -8.5 487-513 4.37 6.16 1.79 4.79 6.14 1.35 -7.9 488-509 4.50 5.49 0.99 4.60 5.52 0.92 -6.2 488-510 5.84 6.58 0.74 5.65 6.67 1.02 -5.4 490-509 5.16 6.01 0.85 5.30 6.12 0.82 -5.8 490-512 5.15 6.37 1.22 5.30 6.28 0.98 -6.4 490-513 4.90 6.10 1.20 5.05 6.05 1.00 -6.1 503-509 1D9 1.39 0.20 1.21 1.41 0.20 -5.5

-80044746

Table 17

RBD peptides with significant protection upon formation of the RBD-mAt10933 complex compared to RBD alone

RBD Leftovers 5 min incubation 10 min incubation RBD- mAT10933 RBD RBD- mAT 10933 RBD D- absorption D- absorption AD D- absorption Dabsorption AD A% D 467-474 2.52 3.16 0.64 2.55 3.17 0.62 -11.7 470-474 1.03 1.46 - 1.03 1.44 - -15.6 0.43 0.41 471-474 0.54 0.89 0.35 0.54 0.89 0.35 -19.5 475-487 3.62 4.50 0.88 3.63 4.48 0.85 -9.6 475-489 3.21 4.48 1.27 3.26 4.53 1.27 -11.8 480-486 1.79 2.06 0.27 1.87 2.07 0.20 -5.1 480-489 2.13 3.67 1.54 2.18 3.69 1.51 -21.2 483-486 0.61 0.78 0.17 0.62 0.78 0.16 -9.3 487-489 0.02 0.40 0.38 0.02 0.39 0.37 -41.6 487-490 0.42 0.90 0.48 0.40 0.84 0.44 -25.6 487-491 0.46 1.05 0.59 0.46 1.03 0.57 -32.0 487-495 0.74 1.59 0.85 0.82 1.57 0.75 -14.8 487-509 6.01 6.99 0.98 6.14 7.02 0.88 -5.7 487-510 6.29 7.37 1.08 6.14 7.44 1.30 -7.0 488-490 0.19 0.22 0.03 0.13 0.23 0.10 -7.4 488-491 0.26 0.37 oh and 0.25 0.36 oh and -12.3

- 81 044746

Table 18

RBD peptides with significant protection upon formation of the RBD-mAt 10920 complex compared to RBD alone

RBD Leftovers 10 min incubation RBD-mAt10920 RBD D-absorption D-absorption Δϋ Δ%ϋ 471-486 4.63 5.40 -0.77 -6.6 475-486 2.74 3.27 -0.53 -6.5 491-513 5.45 6.57 -1.12 -6.6 495-510 4.51 5.43 -0.92 -8.5 495-513 4.41 5.13 -0.72 -5.4 496-515 3.58 4.35 -0.77 -5.4

Table 19

RBD peptides with significant protection when forming an RBD-mAb 10922 complex compared to RBD alone

10 min incubation RBD RBD-mAt10922 RBD Leftovers D-absorption D-absorption Δ D Δ %D 432-441 1.86 2.23 0.37 5.3 442-452 3.52 4.57 1.05 13.0

Table 20

RBD peptides with significant protection upon formation of the RBD-mAb 1093 6 complex compared to RBD alone

RBD Leftovers 10 min incubation RBD-mAt10936 RBD D-absorption D-absorption Δϋ Δ%ϋ 351-360 2.68 3.10 -0.42 -5.9 432-441 1.85 2.23 -0.38 -5.3 442-452 2.55 4.57 -2.02 -25.0 443-452 2.98 4.01 -1.03 -14.2 467-470 0.69 0.84 -0.15 -8.1 471-486 4.73 5.40 -0.67 -5.8 491-513 5.48 6.57 -1.09 -6.4 495-510 4.38 5.43 -1.05 -9.8

-82044746

Table 21

RBD peptides with significant protection upon formation of the RBD-mAt 10954 complex compared to RBD alone

RBD Leftovers 10 min incubation RBD-mAt10954 RBD D-absorption D-absorption AD A%D 400-420 3.67 4.56 -0.89 -5.5 401-420 3.39 4.22 -0.83 -5.5 401-421 3.44 4.28 -0.84 -5.2 406-420 3.32 4.10 -0.78 -7.2 406-421 3.23 4.11 -0.88 -7.6 406-422 3.41 4.16 -0.75 -5.9 407-420 2.86 3.62 -0.76 -7.7 407-422 2.97 3.74 -0.77 -6.6 453-466 1.53 2.23 -0.70 -7.1 453-470 3.63 4.53 -0.90 -6.7 453-471 4.42 5.22 -0.80 -5.6 471-486 4.34 5.40 -1.06 -9.1 472-486 4.47 5.29 -0.82 -7.6 490-512 5.64 6.65 -1.01 -5.9 490-513 5.61 6.57 -0.96 -5.3 491-513 5.26 6.57 -1.31 -7.7 493-512 4.86 5.69 -0.83 -5.7 493-513 4.74 5.72 -0.98 -6.4 495-510 4.77 5.43 -0.66 -6.2 495-513 4.10 5.13 -1.03 -7.6 496-512 3.60 4.60 -1.00 -8.6 496-515 3.43 4.35 -0.92 -6.4

Table 22

RBD peptides with significant protection upon formation of the RBD-mAt 10964 complex compared to RBD alone

RBD Leftovers 10 min incubation RBD-mAt10964 RBD D-absorption D-absorption AD A%D 401-421 3.87 4.84 -0.97 -6.0 406-419 3.34 3.91 -0.57 -5.8 406-420 3.47 4.15 -0.68 -6.3 406-421 3.53 4.22 -0.69 -5.9 406-422 3.66 4.37 -0.71 -5.6 406-424 3.31 4.24 -0.93 -6.5 410-422 3.04 3.56 -0.52 -5.8 471-486 4.65 5.41 -0.76 -6.4 475-489 3.34 4.56 -1.22 -11.3 480-489 2.32 3.19 -0.87 -12.1 487-509 6.38 7.58 -1.20 -7.4 495-513 4.50 5.20 -0.70 -5.2 496-512 4.17 4.80 -0.63 -5.4 496-513 3.90 4.85 -0.95 -7.5

-83044746

Table 23

RBD peptides with significant protection upon formation of the RBD-mAt10977 complex compared to RBD alone

RBD Leftovers 10 min incubation RBD-mAt10977 RBD D-absorption D-absorption AD A%D 351-364 4.82 5.38 -0.56 -5.2 471-486 3.81 5.40 -1.59 -13.6 472-486 4.20 5.29 -1.09 -10.1

Table 24

RBD peptides with significant protection upon formation of the RBD-mAt10984 complex compared to RBD alone

10 min incubation RBD RBD-mAt10984 RBD Leftovers D-absorption D-absorption AD A%D 400-420 3.73 4.56 -0.83 -5.2 401-421 3.47 4.28 -0.81 -5.1 406-420 3.35 4.10 -0.75 -7.0 406-421 3.31 4.11 -0.80 -6.9 406-422 3.47 4.16 -0.69 -5.5 407-420 2.88 3.62 -0.74 -7.5 407-422 2.94 3.74 -0.80 -6.8 453-466 1.51 2.23 -0.72 -7.3 453-470 3.70 4.53 -0.83 -6.2 453-471 4.49 5.22 -0.73 -5.1 471-486 4.45 5.40 -0.95 -8.1 472-486 4.63 5.29 -0.66 -6.1

- 84 044746

Table 25

RBD peptides with significant protection upon formation of the RBD-mAt10986 complex compared to RBD alone

10 min incubation RBD RBD-mAt10986 RBD Leftovers D-absorption D-absorption AD A%D 400-420 3.58 4.56 -0.98 -6.1 400-421 3.60 4.61 -1.01 -5.9 401-420 3.30 4.22 -0.92 -6.1 401-421 3.29 4.28 -0.99 -6.1 401-422 3.44 4.43 -0.99 -5.8 406-420 3.28 4.10 -0.82 -7.6 406-421 3.24 4.11 -0.87 -7.5 406-422 3.35 4.16 -0.81 -6.4 407-420 2.81 3.62 -0.81 -8.2 407-422 2.91 3.74 -0.83 -7.1 453-466 1.53 2.23 -0.70 -7.1 453-470 3.55 4.53 -0.98 -7.3 453-471 4.41 5.22 -0.81 -5.6 471-486 4.13 5.40 -1.27 -10.9 490-510 5.13 6.44 -1.31 -8.6 490-512 5.33 6.65 -1.32 -7.7 490-513 5.25 6.57 -1.32 -7.3 491-513 4.29 6.57 -2.28 -13.3 493-512 4.46 5.69 -1.23 -8.5 493-513 4.62 5.72 -1.10 -7.2 495-513 3.89 5.13 -1.24 -9.3 496-513 3.36 4.53 -1.17 -9.3 496-515 3.05 4.35 -1.30 -9.1

Example 12: Neutralization of wild-type SARS-CoV-2 spike protein and spike protein variants.

To test the ability of anti-SARS-CoV-2 antibodies to neutralize SARS-CoV-2 variants, these antibodies were screened against a panel of VSV pseudotype viruses expressing wild-type spike proteins and their variants. VSV pseudotype viruses were generated by transiently transfecting 293T cells with a plasmid encoding the SARS-CoV-2 spike protein or the same plasmid containing nucleotide sequence changes encoding known amino acid sequence variants of the SARS-CoV-2 spike protein. All plasmids were confirmed by Sanger sequencing. Cells were seeded in 15 cm plates at a rate of 1.2 x 10 ⁷ cells per plate in complete DMEM medium (1000 ml DMEM, Gibco; 100 ml FBS, Gibco; 10 ml PSG, Gibco) one day before transfection in an amount of 15 μg DNA spike gene/plate using 125 µl Lipofectamine LTX, 30 µl PLUS reagent and up to 3 ml OptiMem. 24 h after transfection, cells were washed with 10 ml PBS and then infected with VSVΔ ^G ′ ^mNeon virus at 0.1 MOI in 10 ml Opti-Mem. The virus was incubated with cells for 1 h, with gentle shaking every 10 min. Cells were washed 3 times with 10 ml PBS, then covered with 20 ml infection medium (1000 ml DMEM, Gibco; 10 ml sodium pyruvate, Gibco; 7 ml BSA, Sigma; 5 ml gentamicin, Gibco) before incubation at 37°C. 5% CO ₂ for 24 hours. Pseudovirus supernatant was collected in 250-ml centrifuge tubes on ice, then centrifuged at 3000 rpm for 5 minutes to pellet cell debris, aliquoted on ice, and then frozen at -80°C. Infectivity was tested on Vero cells before use in neutralization assays. This material was called the pseudovirus VSVΔ ^G ' ^mNeon /Spike or VSVΔ ^G ' ^mNeon /Spike_(variant amino acid mutation) (for example, VSVΔ ^G:mNeon /Spike_H49Y).

On day 1, Vero cells were seeded at 80% confluence in T225 flasks, cells were washed with PBS (Gibco: 20012-043), TrypLE was added to detach cells from the flask, and complete DMEM was added to inactivate trypsin. 20,000 Vero cells were seeded in 100 μl of prewarmed complete DMEM per well of a 96-well black polystyrene microplate (Corning: 3904). On 2

- Day 85 044746 pseudovirus VSVΔ ^G ' ^mNeon /Spike was thawed on ice and diluted with infectious medium. Antibodies were diluted in a 96-well U-bottom plate, creating a dilution of each antibody in 210 μl of infection medium at 2-fold assay concentration. 120 μl of diluted antibodies was transferred to a fresh U-bottom plate, and media and IgG1 control antibody were added to each plate. 120 μl of diluted pseudovirus was added to each well, except for control wells containing media. 120 μl of infection medium was added to these wells. The pseudovirus and antibodies were incubated for 30 min at room temperature, and then the medium was removed from the Vero cells. 100 μl of the antibody/pseudovirus mixture was added to the cells and then incubated at 37°C, 5% CO ₂ for 24 hours. On day 3, the supernatant was removed from the wells with cells and replaced with 100 μl of PBS. The plates were read on a SpectraMax i3 with a MiniMax imaging cytometer.

In addition to the neutralization ability assay with the non-replicating VSV-SARS-CoV-2S virus, the antibodies were also assayed with the SARS-CoV-2 virus. Monoclonal antibodies and antibody combinations were serially diluted in DMEM (Quality Biological) supplemented with 10% (v/v) heat-inactivated fetal bovine serum (Sigma), 1% (v/v) penicillin/streptomycin (Gemini Bio-products). and 1% (v/v) L-glutamine (2 mM final concentration, Gibco) (VeroE6 medium) to a final volume of 250 μl. Then, 250 μL of VeroE6 medium containing SARS-CoV-2 (WA-1) (1000 PFU/ml) was added to each serum dilution and to 250 μl of medium as an untreated control. Virus-antibody mixtures were incubated for 60 min at 37°C. After incubation, virus titers in the mixtures were determined using plaque assay. Finally, 50% plaque reduction neutralization titer (PRNT50) values (serum dilutions at which plaque formation was reduced by 50% relative to the untreated control) were calculated by fitting the percent neutralization data to a 4-parameter logistic curve (GraphPad Software, La. -Hoya, California, USA).

Half inhibitory concentration (IC50) of individual monoclonal antibodies against the VSV-SARS-CoV-2 pseudovirus encoding the Wuhan-Hu-1 spike protein (S-wt) sequence (NCBI accession number MN908947.3) and expressing the spike (S) protein, determined in Vero cells (Table 26). Most antibodies exhibited neutralization efficiencies in the picomolar (pM) range, and some exhibited neutralization efficiencies in the nanomolar (nM) range.

Although recombinant ACE2 could mediate neutralization of VSV-spike pseudoparticles as previously reported, its potency was much lower than that of monoclonal antibodies, inferior to the best neutralizing mAb by more than 1000-fold (Fig. 10A). In addition, neutralization assays confirmed the robust neutralizing activity of mAb10987, mAb10989, mAb10933, and mAb10934, including neutralization of SARS-CoV-2 in VeroE6 cells (Figure 10B). All neutralization assays yielded similar potencies for the four mAbs (mAb10987, mAb10989, mAb10933, and mAb10934), and no combination demonstrated synergistic neutralizing activity (Figure 10B).

Table 26

Neutralization efficiency of mAbs (IC50 (M)) against the wild-type strain of VSV-SARS-CoV-2-S pseudoparticles in Vero cells

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Amino acid variants of the spike (S) protein were identified from more than 7000 publicly available SARS-CoV-2 sequences representing isolates circulating worldwide and cloned into VSV pseudoparticles. To evaluate the effect of each variant on the neutralization efficiency of monoclonal antibodies, neutralization assays were performed with pseudoparticles encoding the indicated variant. In table Figure 27 shows the relative neutralization potency of monoclonal antibodies against variant-encoding pseudoparticles compared to SARS-CoV-2 spike protein (S-wt) at a single concentration of 5 μg/mL. The percentage of neutralization compared to S-wt was recorded for each individual antibody and variant. None of the antibodies showed loss of neutralizing ability at a concentration of 5 μg/ml, with the exception of mAb10985 and the R408I variant. These data demonstrate the broad scope of functional neutralization of monoclonal antibodies against SARS-CoV-2 spike protein variants circulating worldwide.

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To further investigate the effect of S protein variants on the neutralization efficiency of monoclonal antibodies, complete neutralization curves were constructed to determine the IC50 value of the most effective neutralizing antibodies against a subset of variants located in the receptor binding domain (RBD) of the S protein. Figure 28 shows the neutralization IC50 values for each pseudoparticle variant. The results of the pseudoparticle neutralization assay were characterized by internal variability of up to 3-fold differences, but this did not indicate a change in neutralization efficiency. These data demonstrate that the antibodies retained their neutralizing ability against a panel of different S protein RBD variants.

Table 27

Relative neutralization of VSV-SARS-CoV-2 S protein variants at 5 μg/ml antibody concentration in Vero cells

mat dt H49Y S50 L V341I N354D S359N V367F K378 R mAT10989 100% 100% 88% 100% 100% 99% 100% 100% mAT10987 100% 100% 96% 99% 100% 99% 100% 100% mAT10933 100% 100% 96% 99% 100% 99% 100% 99% mAT10977 100% 100% 98% 100% 99% 100% 100% 100% mAT10934 100% 100% 95% 100% 100% 99% 100% 99% mAT10964 100% 100% 90% 100% 99% 99% 100% 100% mAT10954 100% 100% 92% 100% 100% 99% 100% 100% mAT10984 100% 100% 95% 100% 99% 99% 100% 99% mAT10986 100% 100% 98% 100% 99% 99% 100% 100% mAT10966 100% 100% 90% 100% 99% 99% 100% 100% mAT10936 100% 100% 96% 100% 99% 99% 100% 100% mAT10955 100% 100% 95% 99% 99% 99% 100% 100% mAT10922 100% 100% 98% 99% 99% 99% 100% 99% mAT10970 100% 100% 99% 100% 100% 100% 100% 99% mAT10956 100% 100% 96% 99% 99% 99% 100% 100% mAT10924 100% 100% 96% 100% 99% 99% 100% 99% mAT10965 100% 100% 96% 100% 99% 100% 100% 100% mAT10971 100% 100% 90% 99% 99% 99% 100% 99% mAT10957 100% 100% 91% 99% 99% 98% 100% 99% mAT10935 100% But But But But 99% But 99% mAT10913 100% 100% 93% 100% 99% 98% 100% 99% mAT10939 100% 100% 93% 98% 99% 100% 100% 99% mAT10967 100% 100% 90% 99% 99% 98% 100% 100% mAT10985 100% 100% 96% 99% 99% 98% 100% 99% mAT10937 100% 100% 92% 99% 100% 98% 100% 99% mAT10920 100% 100% 92% 99% 99% 99% 100% 99% mAT10941 100% 99% 97% 99% 100% 99% 100% 100% mAT10988 100% 100% 99% 100% 99% 98% 100% 100% mAT10923 100% 101% 102 % 97% 103% 105% 104% 103% mAT10915 100% 100% 95% 100% 99% 99% 100% 99% mAT10932 100% 100% 93% 100% 99% 99% 100% 99% mAT10982 100% 100% 94% 99% 99% 99% 100% 100%

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mat R408I Q409 E A435 S K458 R G476 S Y483 A Y508 N H519 R D614 G mAT!0989 100% 101% 100% 99% 99% 100% 100% 97% 100% mAT10987 99% 100% 100% 99% 99% 99% 100% 97% 100% mAT!0933 100% 99% 100% 99% 99% 100% 100% 98% 100% mAT!0977 100% 100% 99% 99% 99% 99% 100% 97% 100% mAT!0934 100% 100% 100% 98% 98% 99% 100% 97% 100% mAT!0964 99% 100% 99% 98% 100% 99% 100% 96% 100% mAT!0954 100% 100% 100% 100% 100% 100% 100% 97% 100% mAT!0984 99% 100% 100% 99% 99% 100% 100% 96% 100% mAT!0986 100% 100% 100% 98% 99% 100% 100% 99% 100% mAT!0966 99% 100% 100% 99% 100% 99% 100% 96% 100% mAT!0936 99% 100% 100% 99% 99% 99% 100% 97% 100% mAT!0955 100% 100% 99% 99% 99% 99% 100% 97% 100% mAT!0922 99% 100% 100% 98% 99% 99% 100% 97% 99% mAT!0970 100% 101% 100% 100% 99% 99% 100% 99% 100% mAT!0956 100% 100% 99% 99% 100% 99% 100% 97% 100% mAT10924 99% 100% 100% 99% 99% 99% 99% 98% 100% mAT!0965 99% 100% 100% 99% 100% 99% 100% 98% 100% mAT!0971 99% 100% 100% 99% 99% 99% 100% 98% 100% mAT!0957 99% 100% 99% 98% 99% 99% 100% 98% 100% mAT!0935 But But But But 98% But 99% But But mAT!0913 99% 100% 100% 99% 98% 99% 99% 97% 100% mAT!0939 99% 100% 99% 98% 97% 98% 100% 96% 100% mAT!0967 99% 99% 99% 98% 99% 98% 100% 97% 100% mAT!0985 26% 100% 100% 99% 99% 100% 99% 97% 99% mAT!0937 100% 99% 99% 99% 99% 100% 99% 98% 100% mAT!0920 99% 100% 100% 99% 98% 100% 99% 98% 100% mAT10941 99% 100% 100% 98% 98% 98% 100% 96% 100% mAT!0988 100% 101% 99% 99% 99% 100% 99% 98% 100% mAT!0923 103% 104% 100% 100% 96% 98% 101% 97% 101% mAT!0915 98% 100% 100% 98% 97% 100% 99% 97% 100% mAT!0932 99% 100% 99% 99% 98% 100% 99% 98% 100% mAT!0982 99% 100% 99% 98% 99% 99% 100% 98% 100%

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Table 28

Biacore.

The equilibrium dissociation constant (KD) for various SARS-COV-2 RBD reagents bound to purified anti-SARS-COV-2 monoclonal antibodies (mAbs) isolated from CHOt cells was determined using a Biacore T200/Biacore 8K biosensor based on surface plasmon resonance in real time. All binding studies were performed in 10 mM running buffer

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HEPES, 150 mM NaCl, 3 mM EDTA and 0.05% v/v. surfactant Tween-20, pH 7.4 (HBS-ET) at 25°C and 37°C. The surface of the Biacore CM5 sensor chip was first modified by amine coupling of a mouse anti-human Fc mAb (Regeneron, mAb2567) to capture the anti-SARS-CoV-2 mAb. Binding studies were performed on the human SARS-CoV-2 extracellular RBD domain expressed with the C-terminal myc-myc-hexahistidine marker (RBD-MMH SARSCOV-2) and the SARS-CoV-2 extracellular RBD domain expressed with the C-terminal IgG2a mice (RBDmFc SARS-CoV-2). The use of these reagents made it possible to test the ability of antibodies to bind monomeric and dimeric RBD peptides, respectively.

Various concentrations of hRBD-MMH SARS-COV-2 (90 nM-3.33 nM, 3-fold dilution) and RBD-mFc SARS-CoV-2 (30 nM-1.11 nM, 3-fold dilution) in working buffer HBS-ET was administered over 3 min at a flow rate of 50 μL/min, while the dissociation of mAbs bound to various SARS-COV-2 RBD reagents was monitored over 6–10 min in HBS-ET running buffer. At the end of each cycle, the anti-SARS-COV-2 RBD mAb capture surface was regenerated using a 12-second injection of 20 mM phosphoric acid when using the mouse anti-human Fc mAb surface. Association rate constants (k _a ) and dissociation rate constants (k d ) were determined by fitting real-time binding sensorgrams to a mass transfer-limited 1:1 binding model using BiaEvaluation software version 3.1 or Biacore Insight Evaluation software version 2.0 or curve fitting software . The binding dissociation equilibrium constant (K _D ) and dissociation half-life (t1/ ₂ ) were calculated from the kinetic rates as:

kd 1п(2)

K _D (M) = - uG/Nmin)»^^

The binding kinetics parameters for various anti-SARS-CoV-2 mAbs binding to various SARS-COV-2 RBD reagents of the present invention at 25°C and 37°C are shown in Table. 29-32, respectively.

Table 29

Parameters of the binding kinetics of RBD-MMH SARS-COV-2 with monoclonal ___________ antibodies against SARS-COV-2-S at 25°C____________

Captured mAb (antibody no.) mAb uptake level (EO) Binding of 90 nM Ag (EO) k _a (1/Ms) M1/s) KD (M) GL (min) mAT10913 287+3 55.9 4.04E+05 2.12E-02 5.26E-08 0.5 mAT10914 310+2 51.1 8.81E+04 3.76E-03 4.26E-08 3.1 mAT10915 310+2 63.2 9.61E+04 1.08E-04 1.1 ZE-09 106.9 mAT10920 307+3 73.9 4.52E+05 1, ZOE-02 2.87E-08 0.9 mAT10921 307+3 61.4 1.01E+05 4.75E-04 4.71E-09 24.3 mAT10922 312.2+1.7 120.2 6.14E+05 1.48E-03 2.41E-09 7.8 mAT10923 283+2 80.4 4.66E+05 6.17E-03 1.32E-08 1.9 mAT10924 319+2 94.6 2.07E+05 1.74E-03 8.40E-09 6.6 mAT10930 284.7 ± 0.7 59.6 1.24E+05 3.34E-03 2.70E-08 3.5 mAT10932 315+3 79.4 8.99E+04 1.21E-04 1.35E-09 95.5 mAT 10933 280+1 99.8 1.52E+06 2.78E-03 1.83E-09 4.2 mAT10934 280+1 103.4 4.82E+06 5.77E-03 1.20E-09 2.0 mAT10935 337+2 107.8 3.93E+05 4.19E-03 1.07E-08 2.8 mAT10936 311+2 107.3 5.45E+05 1.07E-03 1.97E-09 10.8 mAT10937 311+2 102.2 5.72E+05 4.76E-03 8.34E-09 2.4 mAT10938 338+3 61.5 7.27E+04 1.75E-04 2.41E-09 66.0 mAT10939 343+2 82.3 1.63E+05 2.84E-03 1.74E-08 4.1 mAT10940 338+3 103.5 8.01E+05 2.51E-03 3.13E-09 4.6 mAT10941 327+1 92.1 1.20E+05 4.12E-04 3.43E-09 28.0 mAT10954 286.9 ± 3 110.5 4.04E+05 3.64E-04 8.99E-10 31.7 mAT10955 298.3 ± 2.5 88.8 1.61E+05 2.12E-03 1.32E-08 5.4 mAT10956 293.7 ± 0.6 86.6 2.22E+05 4.06E-03 1.82E-08 2.8 mAT10957 286.7 ± 2 93.0 1.38E+05 2.53E-04 1.84E-09 45.7

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mAT10964 259.6 ± 1.2 99.9 1.65E±06 3.90E-04 2.36E-10 29.6 mAT10965 253.1 ± 1.9 63.6 1.24E±05 2.92E-03 2.35E-08 4.0 mAT10966 266.6 ± 3 97.4 2.37E±05 3.65E-04 1.54E-09 31.6 mAT10967 260.2 ± 0.9 70.7 1.24E±05 6.28E-05 5.08E-10 183.9 mAT10969 272.2 ± 1.3 87.1 2.45E±05 3.80E-03 1.55E-08 h,o mAT10970 307.3 ± 1.3 102.8 2.27E±05 Ι,ΙΟΕ-03 4.85E-09 10.5 mAT10971 263.1 ± 1.1 89.3 2.15E±05 3.75E-04 1.74E-09 30.8 mAT10977 305 ± 3 98.5 2.43E±05 2.57E-04 1.06E-09 44.9 mAT10982 267.8 ± 0.5 69.3 1.23E±05 2.06E-03 1.68E-08 5.6 mAT10984 334 ±2.1 117.9 2.04E±05 4.26E-04 2.09E-09 27.1 mAT10985 306.9 ±2.1 113.4 1.44E±06 1.55E-03 1.08E-09 7.5 mAT10986 268.8 ± 0.9 104.3 4.64E±05 1.49E-04 3.21E-10 77.5 mAT10987 270.8 ± 1.3 78.0 5.60E±05 1.20E-02 2D4E-08 1.0 mAT10988 279.2 ± 2.3 63.6 8.29E±05 2.71E-02 3.27E-08 0.4 mAT10989 316.7 ± 1.6 114.3 1.86E±06 2.78E-03 1.50E-09 4.2 mAT10996 414.2 ±2.8 37.5 1.41E±05 2.28E-02 1.61E-07 0.5 mAT10998 212.3 ± 1 17.7 3.54E±05 1.84E-02 5.21E-08 0.6 mAT11000 322.6 ±3.5 73.6 1.09E±06 1D4E-03 1.04E-09 Yu, 1 mAT11002 291.7 ±2.7 13.8 1.65E±05 6.73E-03 4.07E-08 1.7 mAT11004 232.9 ± 0.6 76.4 3.79E±05 3.24E-03 8.54E-09 3.6 m At 11006 277.2 ± 1.1 66.9 9.67E±04 4.40E-04 4.55E-09 26.3 mAT11008 214.9 ± 1.5 40.8 9.30E±04 3.27E-03 3.52E-08 3.5 mAT11010 221.8 ± 1.3 76.8 1.11E±06 2.74E-03 2.47E-09 4.2 mAT1932 205 ± 0.8 5.3 n/s N/S N/S N/S

Table 30

Parameters of the binding kinetics of RBD-MMH SARS-COV-2 with monoclonal antibodies against SARS-COV-2-S at 37°C

Captured mAb (antibody no.) mAb uptake level (EO) Binding of 90 nM Ag (EO) k _a (1/Ms) LD1/S) KD (M) C/2 (min) mAT10913 366±6 49 5.29E±05 5.56E-02 1.05E-07 0.2 mAT10914 401±3 63 2.51E±05 1.58E-02 6.27E-08 0.7 mAT10915 401±3 93 1.57E±05 7.57E-04 4.84E-09 15.3 mAT10920 394±3 73 6.10E±05 3.41E-02 5.60E-08 o, s

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mAT10921 394+3 87 1.60E+05 2.07E-03 1.29E-08 5.6 mAT10922 405.6+ 1.7 130 1.04E+06 9.27E-03 8.89E-09 1.2 mAT10923 355+3 84 6.15E+05 2.76E-02 4.48E-08 0.4 mAT10924 406+5 110 2.99E+05 6.18E-03 2.07E-08 1.9 mAT 10930 373.9 + 3.5 42 2.30E+05 1.87E-02 8.14E-08 0.6 mAT10932 406+4 119 1.43E+O5 6.55E-04 4.57E-09 17.6 mAT 10933 368+3 124 2.37E+06 8.28E-03 3.49E-09 1.4 mAT10934 368+3 117 4.62E+06 2.32E-02 5.02E-09 0.5 mAT10935 430+5 75 4.37E+05 3.74E-02 8.56E-08 o, s mAT10936 402+3 126 9.75E+05 5.51E-03 5.65E-09 2.1 mAT10937 402+3 107 9.68E+05 2.43E-02 2.51E-08 0.5 mAT10938 434+3 100 1.06E+05 1.12E-03 1.05E-08 10.3 mAT10939 439+5 90 2.40E+05 9.46E-03 3.95E-08 1.2 mAT10940 434+3 124 1.42E+06 1.23E-02 8.70E-09 0.9 mAT10941 418+3 134 1.97E+05 1.75E-03 8.87E-09 6.6 mAT10954 371.8 + 2 131 5.68E+05 1.35E-03 2.38E-09 8.6 mAT10955 384.1 + 6.3 81 2.85E+05 1.26E-02 4.43E-08 0.9 mAT10956 383 ± 2.3 89 3.56E+05 1.30E-02 3.65E-08 0.9 mAT10957 322 + 2.1 124 2.44E+05 6.19E-04 2.54E-09 18.7 mAT10964 333.3 + 4.6 121 3.68E+06 2.08E-03 5.64E-10 5.6 mAT10965 326.8+ 1.2 67 2.23E+05 9.19E-03 4.12E-08 1.3 mAT10966 350.2 + 2.9 118 4.40E+05 1.67E-03 3.79E-09 6.9 mAT10967 336 + 2.2 108 1.91E+05 2.62E-04 1.38E-09 44.1 mAT10969 349.5 ± 3 86 4.07E+05 1.59E-02 3.92E-08 0.7 mAT10970 393.8 + 3.4 104 Z,33e+O5 7.58E-03 2.28E-08 1.5 mAT10971 347+ 1.9 116 3.92E+05 9.79E-04 2.50E-09 I,8 mAT10977 341 ± 1.4 122 4.35E+05 1.31E-03 3.01E-09 8.8 mAT10982 347.5+ 1.3 67 1.94E+05 9.42E-03 4.85E-08 1.2 mAT10984 422.5 ± 0.7 144 3.28E+05 1.82E-03 5.55E-09 6.3 mAT10985 395.5 + 2.5 134 2.57E+06 4.23E-03 1.65E-09 2.7 mAT10986 349.3 ± 1.5 129 8.24E+05 5.83E-04 7.07E-10 19.8 mAT10987 354 + 5.3 82 8.38E+05 2.51E-02 3.00E-08 0.5 mAT10988 364.4 + 2.6 52 9.19E+05 5.78E-02 6.29E-08 0.2 mAT10989 405.6+ 1.9 128 2.97E+06 1.16E-02 3.90E-09 1.0 mAT10996 524.3 ± 2.8 43 1.06E+05 1.25E-02 1.19E-07 0.9 mAT10998 271.1 + 0.6 15 2.81E+05 7.54E-03 2.68E-08 1.5 mAT11000 418.2+ 1 87 2.89E+05 9.10E-03 3.14E-08 1.3 mAT11002 370.1 + 2.5 12 2.81E+05 7.54E-03 2.68E-08 1.5 mAT11004 297.8 ± 0.4 79 1.75E+06 1.48E-03 8.48E-10 7.8 mAT11006 350.2+ 1.2 92 6.28E+05 1.48E-02 2.35E-08 0.8 mAT11008 289.4 + 2.7 38 1.42E+05 1.51E-03 1.06E-08 7.6 mAT11010 286.3 ± 0.5 96 1.67E+05 1.45E-02 8.71E-08 0.8 mAT1932 265.3 ± 1.4 5 N/S N/S N/S N/S

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Table 31

Parameters of the binding kinetics of RBD-mFc SARS-CoV-2 with monoclonal antibodies against SARS-COV-2-S at 25°C

Captured mAb (antibody no.) mAb uptake level (EO) Binding of 30 nM Ag (EO) k _a (1/Ms) M1/s) KD (M) t'/2 (min) mAT10913 107+0.4 65 5.00E+06 2.77E-04 5.53E-11 41.7 mAT10914 116+0.8 44 2.59E+05 1.40E-04 5.40E-10 82.5 mAT10915 103+0.2 41 2.83E+05 9.1 ZE-06 3.23E-11 1265.1 mAT10920 116+0.9 69 5.08E+06 2.55E-04 5.02E-11 45.3 mAT10921 104+0.2 39 2.66E+05 3.34E-05 1.25E-10 345.8 mAT10922 111.4 + 0.8 80 3.20E+06 5.64E-05 1.76E-11 204.8 mAT10923 110+1.0 71 3.69E+06 1.35E-04 3.67E-11 85.6 mAT10924 121+0.5 74 8.09E+05 7.63E-05 9.43E-11 151.4 mAT 10930 104.2 + 0.9 61 9.43E+05 1.71E-04 1.81E-10 67.5 mAT10932 121+0.8 60 2.95E+05 2.85E-05 9.67E-11 405.3 mAT10933 108+0.5 72 6.16E+06 6.10E-05 9.89E-12 189.3 mAT10934 113+0.5 70 1D2E+07 1.56E-04 1.39E-11 74.0 mAT10935 128+0.8 88 1.35E+06 1.07E-04 7.94E-11 107.9 mAT10936 117+0.4 74 1.78E+06 5.04E-05 2.83E-11 229.2 mAT10937 106+0.3 67 1.78E+06 5.40E-05 3.04E-11 213.9 mAT10938 128+1.5 47 2.42E+05 1.69E-05 7.02E-11 683.4 mAT10939 127+0.8 67 7.22E+05 8.74E-05 1.21E-10 132.2 mAT10940 102+0.4 67 3.72E+06 4.66E-05 1.25E-11 247.9

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mAT10941 125+0.2 68 3.70E+05 3.48E-05 9.43E-11 331.9 mAT10954 108.8+1 86 2.35E+06 4.78E-05 2, OZE-11 241.6 mAT10955 109.8 + 0.8 76 1.20E+06 9.22E-05 7.71E-11 125.3 mAT10956 104.1 + 0.5 74 1.46E+06 1, ZOE-04 8.87E-11 88.8 mAT10957 104.7 + 0.5 77 1.02E+06 3.35E-05 3.27E-11 344.8 mAT10964 93.3 ± 0.3 70 9.30E+06 3.69E-05 3.97E-12 313.0 mAT10965 94.2 ± 0.8 63 6.94E+05 1.56E-04 2.25E-10 74.0 mAT10966 100.2 + 0.4 73 1.50E+06 3.37E-05 2.24E-11 342.7 mAT10967 93.3 ± 0.2 60 6.64E+05 1.35E-05 2, OZE-11 855.6 mAT10969 111.4 + 0.8 80 4.64E+05 1.00E-04 2.16E-10 115.5 mAT10970 113.4 + 0.7 85 2D9E+06 4.05E-04 1.85E-10 28.5 mAT10971 99 + 0.5 72 1.40E+06 4.09E-05 2.92E-11 282.4 mAT10977 109.1 + 0.4 73 1.82E+06 2.29E-05 1.26E-11 504.4 mAT10982 94.8 + 0.1 59 9.10E+05 8.06E-05 8.86E-11 143.3 mAT10984 121 + 0.6 89 1.39E+06 3.97E-05 2.86E-11 290.9 mAT10985 112.7 + 0.3 77 8.09E+06 8.51E-05 1.05E-11 135.7 mAT10986 94.2 ± 0.5 66 2.70E+06 2.40E-05 8.88E-12 481.3 mAT10987 98 ± 0.7 73 3.19E+06 4.24E-04 1,ЗЗЭ-10 27.2 mAT10988 101.6 + 0.6 69 4.96E+06 5.08E-04 1.02E-10 22.7 mAT10989 112.1 + 0.4 77 1.08E+07 9.63E-05 8.95E-12 119.9 mAT10996 104.2 + 0.9 61 5.62E+05 8.02E-04 1.43E-09 14.4 mAT10998 94.8 + 0.1 59 1.47E+06 3.58E-03 2.44E-09 3.2 mAT11000 112.7 + 0.3 77 1.11E+06 1.27E-04 1D5E-10 90.9 m At11002 121 + 0.6 89 5.54E+05 2.47E-03 4.46E-09 4.7 mAT11004 94.2 ± 0.5 66 6.95E+05 6.40E-05 9.21E-11 180.5 mATPOB 98 ± 0.7 73 3.30E+05 5.21E-05 1.58E-10 221.7 mAT11008 101.6 + 0.6 69 3.90E+05 1.92E-04 4.92E-10 60.2 mAT11010 112.1 + 0.4 77 1.14E+06 8.99E-05 7.89E-11 128.5 mAT1932 97.8 ± 0.2 3 N/S N/S N/S N/S

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Table 32

Parameters of the binding kinetics of RBD-mFc SARS-CoV-2 with monoclonal ___________ antibodies against SARS-COV-2-S at 37°C____________

Captured mAb (antibody no.) mAb10913 mAb uptake level (EO) 147+0.8 Binding of 30 nM Ag (EO) 75 k _a (1/Ms) 6.32E+06 M1/s) 1.73E-03 KD (M) 2.74E-10 t'/2 (min) 6.7 mAT10914 163+1.2 70 6.91E+05 2.20E-04 ZD8E-10 52.5 mAT10915 141+0.6 63 4.41E+05 6.89E-05 1.56E-10 167.6 mAT10920 155+1.1 83 6.31E+06 7.53E-04 1D9E-10 15.3 mAT10921 135+0.3 62 4.58E+05 1.25E-04 2.73E-10 92.4 mAT10922 149.1 ± 1 97 4.60E+06 1.60E-04 3.49E-11 72.2 mAT10923 144+0.8 88 5.53E+06 1.85E-04 3.36E-11 62.4 mAT10924 160+1.1 98 1.17E+06 1.31E-04 1D2E-10 88.2 mAT 10930 142.9 + 0.4 72 1.49E+06 5.97E-04 3.99E-10 19.3 mAT10932 164+ 1.5 89 4.48E+05 6.86E-05 1.53E-10 168.4 mAT 10933 152+ 0.9 89 7.30E+06 7.94E-05 1.09E-11 145.5 mAT10934 151+0.7 87 1.36E+07 2.93E-04 2.16E-11 39.4 mAT10935 171+0.8 101 5.68E+06 4.94E-04 8.69E-11 23.4 mAT10936 161+ 1.0 94 3.81E+06 6.75E-05 1.77E-11 171.1 mAT10937 141+0.6 85 4.47E+06 5.74E-05 1.29E-11 201.2 mAT10938 172+1.2 76 3.78E+05 6.56E-05 1.73E-10 176.1 mAT10939 169+0.6 92 1.06E+06 1.65E-04 1.55E-10 70.0 mAT10940 136+0.6 85 5.54E+06 5.04E-05 9D0E-12 229.2 mAT10941 164+0.8 100 8.02E+05 8.01E-05 1.00E-10 144.2 mAT10954 142.4 + 0.8 105 3.02E+06 1D2E-04 3.69E-11 103.1 mAT10955 146.8 + 0.7 91 1.92E+06 3.88E-04 2.02E-10 29.8 mAT10956 136.6 + 0.4 91 2.17E+06 3.42E-04 1.58E-10 33.8 mAT10957 137.7+1.2 100 1.55E+06 7D9E-05 4.63E-11 160.6 mAT10964 122.5 ± 0.3 84 1.05E+07 1.26E-04 1.20E-11 91.7 mAT10965 125.7+1 81 1.42E+06 3.38E-04 2.37E-10 34.2 mAT10966 137.3 + 1.1 92 2.45E+06 9.93E-05 4.05E-11 116.3 mAT10967 123.3 + 0.9 81 1.45E+06 3,ZZE-05 2.29E-11 346.8 mAT10969 149.1 ± 1 97 8D1E+05 1.41E-04 1.74E-10 81.9 mAT10970 149.9 + 0.6 102 2.18E+06 4.20E-04 1.92E-10 27.5 mAT10971 136.1 + 0.8 90 2.37E+06 9.41E-05 3.97E-11 122.7 mAT10977 145.8 + 0.7 93 2.50E+06 1.07E-04 4.28E-11 107.9 mAT10982 125.5 + 0.8 74 1.23E+06 2.58E-04 2.10E-10 44.8 mAT10984 158.4 + 0.7 110 2.07E+06 8.36E-05 4.04E-11 138.2

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mAT10985 151.8 ±0.7 87 9.36E±06 3.75E-04 4.01E-11 30.8 mAT10986 125 ± 0.7 83 4.59E±06 5.79E-05 1.26E-11 199.5 mAT10987 131.5 ±0.7 87 5.04E±06 3.90E-04 7.75E-11 29.6 mAT10988 138.6 ±0.5 82 8.34E±06 7.90E-04 9.47E-11 14.6 mAT10989 146.1 ±0.6 92 1.38E±07 3.65E-04 2.65E-11 31.6 mAT10996 142.9 ±0.4 72 9.35E±05 2.47E-03 2.64E-09 4.7 mAT10998 125.5 ±0.8 74 8.79E±05 1.97E-02 2.24E-08 0.6 mATPOOO 151.8 ±0.7 87 1.63E±06 2.71E-04 1.66E-10 42.6 mAT11002 158.4 ±0.7 110 5.06E±05 1.65E-02 3.26E-08 0.7 m At11004 125 ± 0.7 83 1.01E±06 1.18E-04 1.17E-10 97.9 mAT11006 131.5 ±0.7 87 3.88E±05 7.65E-05 1.97E-10 151.0 mAT11008 138.6 ±0.5 82 4.64E±05 4.05E-04 8.72E-10 28.5 mAT11010 146.1 ±0.6 92 1.59E±06 8.02E-05 5.05E-11 144.0 mAT1932 128 ± 0.3 5 N/S N/S N/S N/S

Example 14 Antibodies against SARS-CoV-2 block RBD binding to hACE2 as determined by ELISA.

An ELISA-based blocking assay was used to determine the ability of anti-SARS-CoV-2 antibodies to block the binding of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein to its receptor, human angiotensin-converting enzyme 2 (hACE2).

The SARS-CoV-2 protein used in this analysis consisted of a fragment of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (amino acids Arg319 to Phe541) expressed with the C-terminal Fc fragment of human IgG1 (RBD-hFc SARS -CoV-2). The human ACE2 protein used in the experiments was purchased from R&D Systems and consisted of amino acids Gln18 to Ser740 with a C-terminal 10X histidine marker (hACE2-His; NCBI accession number Q9BYF1).

Experiments were performed according to the following procedure. Anti-penta-His monoclonal antibody (Qiagen) was applied to a 96-well microtiter plate at a concentration of 1 μg/ml in PBS overnight at 4°C. The hACE2-His receptor was added at a concentration of 0.2 μg/ml in PBS and bound for 2 h at room temperature (RT). Nonspecific binding sites were then blocked using 0.5% (w/v) BSA in PBS. In other microtiter plates, a constant amount of 100 pM SARS-CoV-2 RBD-hFc protein was coupled to anti-SARS-COV-2 antibodies and IgG1 isotype control antibody diluted in PBS +0.5% BSA to concentrations ranging from 0.0008 nM to 50 nM. After an hour's incubation, the mixture solutions were transferred to a microtiter plate with immobilized hACE2-His. After 1.5 h of incubation at room temperature, wells were washed and plate-bound SARS-CoV2 was detected using horseradish peroxidase (HRP)-conjugated goat anti-human IgG antibody (Jackson). The plates were then developed using TMB substrate solution (BD Biosciences, #555214) according to the manufacturer's recommendations, and absorbance was measured at 450 nm on a Victor X5 plate reader.

Binding data were analyzed using a sigmoidal dose response model in Prism™ software (GraphPad). The calculated IC50 value, defined as the concentration of antibody required to reduce 50% the binding of SARS-CoV-2 RBD-hFc to hACE2-His immobilized on the plate, was used as an indicator of blocking efficiency. Percent blocking was determined based on the background-corrected binding signal observed at the highest antibody concentration assayed using this formula and was reported for all antibodies assayed:

_0/ [Experimental signal _{(maximum conc} . _Ab ) Blocked = background signal,^,]

II [MAXIMUM SIGNAL(hEGF.mFc _only ) - background '

SIGNAL (buffer)]

Antibodies that blocked binding by 50% or less at the highest concentration tested were classified as nonblocking and IC50 values for these antibodies were not recorded.

The ability of anti-SARS-CoV-2 antibodies to block the binding of the SARS-CoV-2 RBD to human ACE2 was assessed using a blocking ELISA. In this assay, 100 pM SARS-CoV-2 RBD-hFc was titrated with a wide range of anti-SARS-CoV-2-S antibody concentrations and the inhibition of RBD binding to hACE2-His in the presence of antibody was assessed. RBD-hFc bound to the plate was detected using an anti-hFc antibody conjugated to HRP.

Summary of Blocking IC50 and Maximum Blocking at Largest Analyzes

- 97 044746 concentrations of antibodies against SARS-CoV-2-S are given in table. 33 and the blocking curves are shown in FIG. 1-8. Forty-four of the 46 antibodies analyzed demonstrated blocking the binding of RBD.hFc to hACE-2 in a concentration-dependent manner. IC50 values ranged from 41 pM to 4.5 nM, and maximum blocking values ranged from 55% to approximately 100% at the highest antibody concentration assayed. Two antibodies out of 46 analyzed did not show blocking activity under the assay conditions. The nonspecific isotype control antibody did not demonstrate blocking activity, as expected.

Table 33

Blocking ability of anti-SAR-COV-2 antibodies on the binding of RBD-hFc spike protein to immobilized human ACE-2

Blocking Blocking Cycle number binding 100 pM binding 100 pM mat analysis (RBD).hFc with ACE2, (RBD).hFc with ACE2, 1С ₅₀ , m % blocking mAT10913 1 2D7E-10 80 mAT10914 1 9.80E-10 93 mAT10915 1 3.21E-10 99 mAT10920 1 3.38E-10 95 mAT10920 3 1.39E-10 87 mAT10921 1 4,ЗЗЭ-10 99 mAT10921 3 5.07E-10 94 mAT10922 2 6.65E-11 97 mAT10923 1 1.49E-10 94 mAT10923 3 1.84E-10 85 mAT10924 1 1.63E-10 98 mAT10924 2 1.27E-10 98 mAT 10930 2 2.82E-10 86 mAT10932 1 3.73E-10 99 mAT10933 1 7.07E-11 99 mAT10933 3 6.53E-11 95 mAT 10933 2 5.22E-11 101 mAT10934 1 6.60E-11 96 mAT10934 3 5.97E-11 98 mAT10934 2 4.80E-11 96 mAT10935 1 1.02E-10 99 mAT10935 2 6.94E-11 98 mAT10936 1 8.75E-11 95 mAT10936 2 7D0E-11 97 mAT!0937 1 6.49E-11 99 mAT10938 1 2.75E-10 99 mAT10939 1 1.75E-10 97 mAT10939 3 2.63E-10 93 mAT10940 1 6.52E-11 92 mAT10941 1 2.27E-10 100

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mAT10941 2 2.06E-10 100 mAT10954 2 7D1E-11 95 mAT10955 2 1.41E-10 97 mAT10956 2 1.85E-10 99 mAT10957 2 1.69E-10 99 mAT10964 3 6.83E-11 93 mAT10964 2 6.25E-11 95 mAT10965 2 2DZE-10 97 mAT10966 2 1.60E-10 99 mAT10967 2 2.80E-10 98 mAT10969 3 2D5E-10 95 mAT10970 2 1.07E-10 97 mAT10971 2 1.49E-10 98 mAT10977 3 8.71E-11 77 mAT10977 2 7D1E-11 65 mAT10982 2 1D6E-10 93 mAT10984 2 7.75E-11 90 mAT10985 3 6.96E-11 97 mAT10985 2 4D1E-11 99 mAT10986 2 7.54E-11 98 mAT10987 3 2.85E-10 93 mAT10987 2 1.81E-10 95 mAT10988 2 8.64E-11 95 mAT10989 3 5.91E-11 96 mAT10989 2 4.28E-11 98 mAT10996 3 6D0E-09 71 mAT10998 h 4,ZOE-09 55 mAT11000 3 4.50E-09 75 mAT11002 h N/B 7 mAT11004 3 N/B 9 mAT11006 3 2.20E-10 85 mAT11008 3 1.49E-09 93 mAT11010 3 1D7E-10 83 mAT193250, 1 - -8 control IgGl mAb193250, control IgGl 3 - -19 mAb193250, control IgGl 2 - -15

Note: RBD-hFc at a concentration of 100 pM was titrated with antibodies against SARS-COV-2-S in serial dilutions from 50 nM, bound RBD-hFc on immobilized hACE2 with a 10x histidine marker was detected using an anti-hFc antibody conjugated to HRP. N/A - no blocking detected.

Example 15. Cross competition between mAb10987, mAb10989, mAb10933 and mAb10934.

mAb10987, mAb10989, mAb10933 and mAb10934 were examined in competitive cross-linking assays (Fig. 11), identifying several pairs of non-competing mAbs with picomolar neutralizing potency that can be combined to produce antibody mixtures, for example, mAb10987 and mAb0933.

Anti-SARS-CoV-2-S mAb epitopes were combined in a sandwich format with pre-mixing of competing mAbs, pairwise combining them with each other upon binding to the SARS-CoV-2 RBD-MMH protein using a ForteBio biolayer interferometry device

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Octet HTX (Molecular Devices ForteBio LLC, Fremont, CA, USA) with running buffer 10 mM HEPES, 150 mM NaCl, 0.05% (v/v) Tween-20, pH 7.4, 1 mg/ml BSA . Analyzes were performed at 30°C and continuous stirring at 1000 rpm. After obtaining an initial baseline signal in 20 μg/mL running buffer, anti-COVID19 mAb was captured on the anti-human Fc (AHC) biosensor tips for 300 s. To block the remaining free unsaturated binding sites on the AHC tips of the biosensors, all sensors were exposed to a blocking solution containing 100 μg/ml nonspecific IgG1 for 240 s. After this, the biosensors were immersed in wells containing a solution of pre-mixed 100 nM SARS CoV-2 RBD-MMH protein and 600 nM of the second mAb binding site on the anti-COVID19 mAb for 300 s. At each step, the binding response was recorded, and the specific signal was normalized by subtracting the self-blocking control competitive mAb from the data set. Data analysis was performed using Octet Data Analysis HT 10.0 software using the Epitope Binning procedure.

Comparison of cross-competitive binding assays with the HDX-MS results described above provided structural insight into the mechanism by which non-competitive antibody pairs can simultaneously bind the RBD and thus may be ideal partners for a therapeutic antibody mixture. mAb10987 and mAb10933 represent such a pair of antibodies. The target of mAb10933 is the spine-loop region at one edge of the ACE2 interaction surface. Within this region, the residues showing the most significant HDX protection by mAb10933 face up, suggesting that the Fab region of mAb10933 bound the RBD from the upstream direction, where mAb10933 significantly conflicted with ACE2. To avoid competition with mAb10933, mAb10987 bound only to HDX-defined protected regions at the front or bottom left (Fig. 12, front view of mAb10987). This is consistent with the neutralization data described above, as mAb10987 may be located in a position that is likely to interfere with ACE2.

Example 16 Determination of the structure of the spike protein associated with antibodies.

To better understand the binding of mAb10933 and mAb10987 to the RBD of the spike protein, structural analysis was performed using cryoelectron microscopy (cryoEM). Fab fragments of mAb10933 and mAb10987 were isolated using the FabALACTICA kit (Genovis). 600 μg Fab mAb10933 and 600 μg Fab mAb10987 were mixed with 300 μg RBD SARS-CoV-2-S and incubated on ice for ~1 hour, then injected into a Superdex 200 enhanced gel filtration column equilibrated to 50 mM Tris, pH 7.5, 150 mM NaCl. Peak fractions containing the mAb10933 Fab - mAb10987 Fab - RBD complex were collected and concentrated using a 10 kDa MWCO centrifugal filter. To obtain a cryoEM array, the protein sample was diluted to 1.5 mg/mL and 0.15% Amphipol PMAL-C8 was added. 3.5 μl of protein was applied to an UltrAufoil grid immediately cleaned with plasma (1.2/1.3, 300 mesh/inch). Excess solution was removed with filter paper and immersed frozen in liquid ethane using a Vitrobot Mark IV. The cryoEM array was transferred to a Titan Krios (Thermo Fisher) equipped with a K3 detector (Gatan). Movies were collected using an EPU (Thermo Fisher) at 105,000x magnification, corresponding to a pixel size of 0.85 A. A dose rate of 15 electrons per pixel per second was used, and each video recording was 2 seconds long, corresponding to a total dose of ~40 electrons per A2 .

All cryoEM data processing was performed using cryoSPARC version 2.14.2. 2821 videos were aligned using fragment motion correction and fragment CTF estimation. The 2197 aligned micrographs were selected for further processing based on the estimated defocus values and CTF fitting resolutions. An initial set of particles selected by the small object picker was subjected to 2D classification to generate patterns for template selection. The 989,553 particles selected by template selection were subjected to multiple rounds of 2D classification to remove unbound FAB and particles containing incomplete complex. Ab initio reconstruction with three classes resulted in one class containing 61,707 particles that corresponded to the mAb10933 Fab -mAb10987 Fab - RBD complex. Heterogeneous refinement of particles of this class followed by inhomogeneous refinement resulted in a map with a resolution of 3.9 A (FSC=0.143) containing 48140 particles, which was used to build the model. Models of the RBD (taken from PDB code 6M17) and two Fabs (taken from previous antibody structures, except for the lambda light chain of mAb10987, which was obtained from PDB code 5U15) were manually placed onto this map. These models were then manually rebuilt using Coot and refined in real space by comparing them to a map using Phenix.

Confirming the above data, single-particle cryo-EM of the SARSCoV-2 spike RBD complex bound to the Fab fragments of mAb10933 and mAb10987 showed that the two antibodies in this mixture could simultaneously bind to different regions of the RBD (Figs. 13A, 13B and 14). A 3D reconstructed map of the complex with a nominal resolution of 3.9 Å shows that both Fab fragments bound to different epitopes on the RBD, confirming that they are not competing antibodies. mAb10933 bound at the top of the RBD, largely overlapping the ACE2 binding site.

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On the other hand, the epitope for mAb10987 was located on the side of the RBD, away from the epitope of mAb10933, and had virtually no overlap with the ACE2 binding site.

Example 17: Cross-competition between mAbs against SARS-CoV-2-S.

Binding competition between anti-SARS-CoV-2-S monoclonal antibodies was determined using real-time label-free biolayer interferometry on the Octet HTX biosensor platform (Pall ForteBio Corp.). The entire experiment was performed at 25°C in a buffer of 10 mM HEPES, 150 mM NaCl, 3 mM EDTA and 0.05% v/v. surfactant Tween-20, 1 mg/ml BSA, pH 7.4 (HBS-EBT) while shaking the plate at 1000 rpm. To assess whether two mAbs are able to compete with each other for binding to the corresponding epitopes on the extracellular RBD domain of SARS-COV-2-S expressed with a C-terminal myc-myc-hexahistidine marker (RBDMMH SARS-COV-2), ~ 0.51 nm RBD-MMH SARS-COV-2-S was first captured on Octet biosensor tips coated with anti-penta-His antibody (Fortebio Inc, #18-5122) by dipping the biosensor tips for 1 minute into wells containing 10 μg /ml RBD-MMH SARS-COV-2-S solution. The SARS-COV-2-S RBD-MMH-capturing biosensor tips were then loaded with the first anti-SARS-CoV-2-S monoclonal antibody (hereafter referred to as mAb-1) by dipping into wells containing 50 μg/mL mAb-1 solution. for 5 min. The biosensor tips were then immersed in wells containing a 50 μg/mL solution of a second monoclonal antibody against SARS-CoV-2 (hereinafter referred to as mAb-2) for 5 min. The biosensor tips were washed in HBS-ET buffer after each experimental step. The binding reaction was monitored in real time throughout the experiment, recording the binding response at the end of each step. The binding reaction of mAb-2 with RBD-MMH SARS-COV-2, previously complexed with mAb-1, was compared and the competitive/non-competitive behavior of various monoclonal antibodies against SARS-CoV-2 was determined, as shown in Table. 34.

Table 34

Cross-competition between antibodies against SARS-CoV-2-S

mAT-1 mAb-2, competing with mAb-1 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT10998 mAT!0984 mATPO About mAT!0921 mAT!0971 mAT!0938

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mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT10941 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT11002 mAT!0933 mAT!0940 mAT!0922 mAT!1004 mAT!0937 mAT!0936 mAT!0934 mAT10924 mAT10977 mAT10989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT10998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT!0915

- 102044746

mAT10989 mAT10965 mAT10967 mAT10986 mAT10955 mAT10954 mAT10933 mATPOOO mAT10985 mAT10937 mAT10936 mAT10934 mAT10977 mAT10924 mAT109 20 mAT10913 mAT10923 mAT10930 mAT10969 mAT10988 mAT10964 mAT10996 mAT10966 mAT10998 mAT10984 mATPOB mAT10921 mAT10971 mAT109 38 mAT10932 mAT10970 mAT10957 mAT10956 mAT10941

- 103 044746

mAT10939 mAT10935 mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT10986 mAT!0955 mAT!0954 mAT!0933 mAT!0987 mAT!0940 mAT!0922 mAT11004 mAT!0937 mAT!0936 mAT!0934 mAT10920 mAT!0977 mAT!0924 mAT!0989 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT10996 mAT!0966 mAT10998 mAT!0984 mATPOB

- 104044746

mAT10921 mAT10971 mAT10938 mAT10932 mAT10970 mAT10957 mAT10956 mAT10941 mAT10939 mAT10935 mAT10914 mAT10982 mAT11008 mAT10915 mAT10965 mAT10967 mAT10986 mAT10955 mAT10954 mAT11002 mAT10933 mAT10987 mAT10940 mAT10922 mAT11004 mAT10937 mAT10936 mAT10934 mAT10913 mAT10977 mAT10924 mAT10989 mAT10920 mAT10923

-105044746 mAT!0930 mAT10969 mAT!0988 mAT10964 mAT!0996 mAT10966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!09 32 mAT!0970 mAT!0957 mAT!0956 mAT10941 mAT10939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0933 mAT11004 mAT!0937 mAT!0936

- 106 044746

mAT!0934 mAT10923 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT10913 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955

- 107 044746

mAT!0954 mAT11002 mAT!0933 mAT11004 mAT!0937 mAT10936 mAT!0934 mAT10930 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982

- 108 044746

mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT10955 mAT!0954 mAT11002 mAT!0933 mAT!0937 mAT!0936 mAT!0934 mAT10969 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0988 mAT!0964 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941

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mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT10915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0933 mAT!0985 mAT!0937 mAT!0936 mAT!0934 mAT!0988 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971

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mAT!0938 mAT10932 mAT!0970 mAT!0957 mAT!0956 mAT10941 mAT!0939 mAT!0935 mAT10914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT!0933 mAT!0936 mAT!0934 mAT10964 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT10988 mAT!0996 mAT10966 mAT!0998 mAT!0984

-Ill 044746

mATPOB mAT10921 mAT10971 mAT10938 mAT10932 mAT10970 mAT10957 mAT10956 mAT10941 mAT10939 mAT10935 mAT10914 mAT10982 mAT11008 mAT10915 mAT10965 mAT10967 mAT10986 mAT10955 mAT10954 mAT11002 mAT10933 mAT10936 mAT10934 mAT10996 mAT10977 mAT10924 mAT10989 mAT10920 mAT10913 mAT10923 mAT10930 mAT10969 mAT10988

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mAT!0964 mAT10966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0933 mAT!0985 mAT!0934 mAT!0966 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913

-IZ044746

mAT10923 mAT10930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!097 0 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT! 0935 mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0933 mAT!0985 mAT!0934 mAT!0998 mAT!0977

- 114 044746 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0984 m AtPOOB mAT!0921 mAT!0971 mAT!0938 mAT !0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!098 6 mAT!0955 mAT!0954 mAT11002

- 115 044746

mAT!0985 mAT!0936 mAT!0984 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986

- 116 044746

mAT10955 mAT10954 mAT11002 mAT10985 mATPOB mAT10977 mAT10924 mAT10989 mAT10920 mAT10913 mAT10923 mAT10930 mAT10969 mAT10988 mAT10964 mAT10996 mAT10966 mAT10998 mAT10984 mAT10921 mAT10971 mAT10938 mAT10932 mAT10970 mAT10957 mAT10956 mAT10941 mAT10939 mAT10935 mAT10914 mAT10982 mAT11008 mAT10915 mAT10965

- 117 044746

mAT10967 mAT!0986 mAT!0955 mAT!0954 mAT!1002 mAT10933 mAT!0985 mAT10921 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT10964 mAT10996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982

- 118 044746

mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0985 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0971 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935

- 119044746

mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0985 mAT!0938 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941

- 120 044746

mAT10939 mAT10935 mAT10914 mAT10982 mAT11008 mAT10915 mAT10965 mAT10967 mAT10986 mAT10955 mAT10954 mAT11002 mAT10985 mAT10932 mAT10977 mAT10924 mAT10989 mAT10920 mAT10913 mAT10923 mAT10930 mAT10969 mAT10988 mAT10964 mAT10996 mAT10966 mAT10998 mAT10984 mATPOB mAT10921 mAT10971 mAT10938 mAT10970 mAT10957

- 121 044746

mAT!0956 mAT10941 mAT!0939 mAT!0935 mAT!0914 mAT10982 mAT!1008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0985 mAT10970 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938

- 122 044746

mAT!0932 mAT!0957 mAT10956 mAT!0941 mAT!0939 mAT10935 mAT!0914 mAT!0982 mAT!1008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0985 mAT!0936 mAT10957 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB

- 123 044746

mAT10921 mAT10971 mAT10938 mAT10932 mAT10970 mAT10956 mAT10941 mAT10939 mAT10935 mAT10914 mAT10982 mAT11008 mAT10915 mAT10965 mAT10967 mAT10986 mAT10955 mAT10954 mAT11002 mAT10985 mAT10956 mAT10977 mAT10924 mAT10989 mAT10920 mAT10913 mAT10923 mAT10930 mAT10969 mAT10988 mAT10964 mAT10996 mAT10966 mAT10998

- 124 044746

mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT10932 mAT!0970 mAT!0957 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0985 mAT10941 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996

- 125 044746

mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0985 mAT10939 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988

- 126 044746

mAT10964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!094 1 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT! 0915 mAT10965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0977 mAT!0924 mAT!0989 mAT10920 mAT!0935 mAT!0913 mAT!0923 mAT!0930 mAT10969

- 127044746

mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0985 mAT10914 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923

- 128 044746

mAT!0930 mAT10969 mAT!0988 mAT!0964 mAT10996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0933 mAT!0985 mAT10982 mAT!0977 mAT!0924 mAT!0989

- 129044746

mAT10920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT10996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!093 2 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mAT!0985 mAT11008 mAT!0977

- 130 044746 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT10988 mAT!0964 mAT!0996 mAT10966 mAT!0998 m At!0984 matPOB mat!0921 mat!0971 mat!0938 mat! 0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002

- 131 044746

mAT10933 mAT!0985 mAT!0915 mAT!0924 mAT!0989 mAT!0920 mAT10913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT!0965 mAT!0967 mAT!0986 mAT!0955

- 132 044746

mAT10954 mAT11002 mAT10985 mAT10965 mAT10924 mAT10989 mAT10920 mAT10913 mAT10923 mAT10930 mAT10969 mAT10988 mAT10964 mAT10996 mAT10966 mAT10998 mAT10984 mATPOB mAT10921 mAT10971 mAT10938 mAT10932 mAT10970 mAT10957 mAT10956 mAT10941 mAT10939 mAT10935 mAT10914 mAT10982 mAT11008 mAT10915 mAT10967 mAT10986

- 133 044746

mAT!0955 mAT!0954 mAT11002 mAT!0985 mAT!0967 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008 mAT!0915 mAT!0965

- 134 044746

mAT10986 mAT10955 mAT10954 mAT11002 mAT!0985 mAT10924 mAT!0989 mAT!0920 mAT10913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0986 mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT10935 mAT!0914 mAT10982 mAT11008 mAT!0915

-135044746

mAT10965 mAT10967 mAT10955 mAT10954 mAT11002 mAT10985 mAT10955 mAT10924 mAT10989 mAT10920 mAT10913 mAT10923 mAT10930 mAT10969 mAT10988 mAT10964 mAT10996 mAT10966 mAT10998 mAT10984 mATPOB mAT10921 mAT10971 mAT10938 mAT10932 mAT10970 mAT10957 mAT10956 mAT10941 mAT10939 mAT10935 mAT10914 mAT10982 mAT11008

- 136044746

mAT!0915 mAT10965 mAT!0967 mAT!0986 mAT10954 mAT11002 mAT!0985 mAT!0924 mAT10989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mAT10954 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT10941 mAT!0939 mAT10935 mAT!0914 mAT10982

- 137044746

mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT11002 mAT10985 mAT11002 mAT!0977 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0964 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!0956 mAT!0941 mAT!0939 mAT!0935 mAT!0914 mAT!0982 mAT11008

- 138 044746

mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT10954 mAT!0933 mAT!0985 mAT!0936 mAT!0933 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0996 mAT!0966 mATPOOB mAT!0914 mAT11008 mAT11002 mAtIIOOO mAT!0937 mAT!0936 mAT!0934 mAtIIOOO mAT!0924 mAT!0933 mAT!0985 μΑτΙΙΟΙΟ

- 139044746

mAT!0985 mAT!0924 mAT!0969 mAT!0996 mAT!0966 mAT!0998 mAT!0984 mATPOB mAT!0921 mAT!0971 mAT!0938 mAT!0932 mAT!0970 mAT!0957 mAT!095 6 mAT!0941 mAT!0935 mAT!0914 mAT !0982 mAT11008 mAT!0915 mAT!0965 mAT!0967 mAT!0986 mAT!0955 mAT!0954 mAT11002 mATPOOO μΑτΙΙΟΙΟ μΑτΙΙΟΙΟ mATPOOO mAT!0985 mAT!0987 mAT!0989 mAT!0920 mAT!0940

- 140 044746

mAT10922 mAT11004 mAT10937 mAT10936 mAT10934 mAT10940 mAT10977 mAT10989 mAT10920 mAT10987 mAT10922 mAT11004 mAT10937 mAT10936 mAT10934 mAT10922 mAT10977 mAT10989 mAT10920 mAT10987 mAT10940 mAT11004 mAT10937 mAT10936 mAT10934 mAT11004 mAT10977 mAT10989 mAT10920 mAT10913 mAT10923 mAT10987 mAT10940 mAT10922 mAT10937 mAT10936

- 141 044746

mAT!0934 mAT!0937 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT10913 mAT!0923 mAT!0930 mAT!0969 mAT!0933 mAT!0987 mAT!0940 mAT!0922 mAT!1004 mAT!0936 mAT!0934 mAT!0936 mAT!0977 mAT!0924 mAT!0989 mAT!0920 mAT!0913 mAT!0923 mAT!0930 mAT!0969 mAT!0988 mAT!0964 mAT!0998 mAT!0970 mAT11002 mAT!0933 mAT!0987 mAT!0940 mAT!0922

- 142 044746

mAT11004 mAT10937 mAT10934 mAT10934 mAT10977 mAT10924 mAT10989 mAT10920 mAT10913 mAT10923 mAT10930 mAT10969 mAT10988 mAT10964 mAT10996 mAT10966 mAT10933 mAT10987 mAT10940 mAT10922 mAT11004 mAT10937 mAT10936

Example 18: pH sensitivity of anti-SARS-CoV-2-S monoclonal antibodies binding to monomeric SARS-CoV-2-S RBD reagents measured at 37°C.

Dissociation rate constants (kd) for various anti-SARS-CoV2-S monoclonal antibodies in pH 7.4, pH 6.0 and pH 5.0 buffers were determined using a Biacore T200 real-time surface plasmon resonance (SPR) biosensor . All binding studies were performed at 37°C using three running buffers: (i) PBS, 0.05% v/v. surfactant Tween-20, pH 7.4 (PBS-T-pH 7.4) (ii) PBS, 0.05% v/v. surfactant Tween-20, pH 6.0 (PBS-T-pH 6.0) and (iii) PBS, 0.05% v/v. surfactant Tween-20, pH 5.0 (PBS-T-pH 5.0). The surface of the Biacore CM5 sensor chip was first modified by amine coupling with a mouse anti-human Fc mAb (Regeneron) to capture anti-SARS-CoV-2-S monoclonal antibodies. Binding studies were performed on the extracellular RBD domain of human SARS-COV-2-S expressed with a C-terminal myc-myc-hexahistidine marker (RBD-MMH SARS-COV-2). Unit concentrations of SARS-COV-2-S RBD-MMH (90 nM) in PBS-T-pH 7.4 buffer were injected at a flow rate of 25 μL/min for 3 minutes, followed by dissociation of bound SARS-COV-2 RBD-MMH -S in working buffers PBS-T-pH 7.4, PBS-T-pH 6.0 or PBST-pH 5.0 for 5 min.

Dissociation rate constants (k _d ) in four working buffers with different pH were determined by fitting real-time binding sensorgrams to a 1:1 binding model using curve fitting software Scrubber 2.0c. The dissociative half-life (t1/ ₂ ) was calculated from kd values as follows:

u/ ί A ^,P(2) 1½ (min)

kd and t1/ ₂ values for binding of SARS-COV-2-S RBD-MMH to various anti-SARS-CoV-2-S monoclonal antibodies in PBS-T-pH 7.4 followed by dissociation in PBS-T-pH 7, 4 and PBS-TpH 6.0 at 37°C are shown in table. 35. kd and t1/ ₂ values for binding of SARS-COV-2-S RBD-MMH to various anti-SARS-CoV-2-S monoclonal antibodies in PBS-T-pH 7.4 followed by dissociation in PBS-T-pH 7.4 and PBS-T-pH 5.0 at 37°C are shown in table. 36. Comparison of half-life (tVz) of SARS-COV-2 RBD-MMH in pH 7.4, pH 6.0 and pH 5.0 buffers.

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Binding of SARS-COV-2-S RBD-MMH to anti-SARS-CoV-2-S monoclonal antibodies in buffer

Table 35

PBS-T-pH 7.4 and dissociation in PBS-T-pH 7.4 and pH 6.0 buffer at 37°C

Working buffer: PBS-T, pH 7.4 at 37 °C. Working buffer: PBS-T, transition to pH 6.0 at 37°C The ratio is not 1½ Captured mAb mAb uptake level (EO) Binding of 90 nM RBD.mmh (EO) kd (1/s) 1½ (min) mAb uptake level (EO) Binding of 90 nM RBD.mmh (EO) kd (1/s) 1½ (min) pH 7.4 / pH 6.0 mAT!0913 427 69 4,ZOE-02 0.3 421 67 4.38E-02 0.3 1 mAT!0914 388 69 9.41E-03 1.2 386 62 1D6E-02 1 1.2 mAT10915 319 84 7.43E-04 15.5 312 88 1.51E-03 7.7 2 mAT!0932 432 133 6.60E-04 17.5 438 131 1.28E-03 9 1.9 mAT!0933 360 124 7.85E-03 1.5 353 119 8.53E-03 1.4 1.1 mAT!0934 341 107 1.74E-02 0.7 334 108 2D1E-02 0.5 1.2 mAT10935 407 76 2.78E-02 0.4 404 72 1.71E-02 0.7 0.6 mAT!0936 381 124 5.29E-03 2.2 375 120 8.69E-03 1.3 1.6 mAT!0937 330 94 2.09E-02 0.6 323 98 2.09E-02 0.6 1 mAT!0924 385 111 5.69E-03 2 379 110 1.20E-02 1 2.1 mAT10938 407 95 1.05E-03 eleven 407 90 2.99E-03 3.9 2.8 mAT10940 343 119 1.08E-02 1.1 339 127 1.04E-02 1.1 1 mAT10941 398 129 1.65E-03 7 396 127 2.04E-03 5.7 1.2 mAT10920 383 79 2.47E-02 0.5 380 73 5.39E-02 0.2 2.2 mAT!0921 345 89 1.79E-03 6.5 339 92 2.01E-02 0.6 11.3 mAT!0923 355 87 2.35E-02 0.5 349 88 2.43E-02 0.5 1 mAT!0939 410 90 9.48E-03 1.2 412 83 1D8E-02 1 1.2 mAT!0922 251 85 9.07E-03 1.3 240 92 9.61E-03 1.2 1.1 mAT!0930 377 50 1.92E-02 0.6 372 46 1.67E-02 0.7 0.9 mAT10982 389 79 9.90E-03 1.2 387 74 7.72E-03 1.5 0.8 mAT!0984 378 133 1.71E-03 6.8 370 135 1.94E-03 5.9 1.1 mAT10985 457 172 3.63E-03 3.2 464 172 ZD9E-OZ 3.6 0.9 mAT!0986 413 155 6.29E-04 18.4 411 152 1.24E-03 9.3 2 mAT!0987 379 105 2.37E-02 0.5 372 109 1.83E-02 0.6 0.8 mAT10988 467 109 4.35E-02 0.3 469 103 5.37E-02 0.2 1.2 mAT!0989 382 126 9.32E-03 1.2 375 119 7.36E-03 1.6 0.8 mAT!0970 340 93 7.65E-03 1.5 334 96 6.37E-03 1.8 0.8 mAT!0971 350 125 9.44E-04 12.2 342 125 1.27E-03 9.1 1.3 mAT!0964 380 140 1.94E-03 6 379 137 2.51E-03 4.6 1.3 mAT!0965 290 65 8.66E-03 1.3 281 70 9.47E-03 1.2 1.1

- 144 044746

mAT!0966 417 152 1.60E-03 7.2 409 149 1.41E-03 8.2 0.9 mAT!0967 372 118 2.98E-04 38.8 367 115 3.45E-04 33.5 1.2 mAT!0954 336 118 1.74E-03 6.6 331 124 2.70E-03 4.3 1.6 mAT!0955 404 100 1.22E-02 0.9 403 97 1.46E-02 0.8 1.2 mAT10956 452 114 1.25E-02 0.9 446 106 1.50E-02 0.8 1.2 mAT!0957 388 136 5.80E-04 19.9 382 140 7.67E-04 15.1 1.3 mAT!0977 293 44 1.59E-02 0.7 285 44 3.39E-02 0.3 2.1 mAT!0969 340 72 1.86E-02 0.6 336 71 1.01E-02 1.1 0.5 mAT10996 408 35 4.69E-02 0.2 405 37 4.37E-02 0.3 0.9 mAT!0998 308 20 2.86E-02 0.4 307 19 2.84E-02 0.4 1 mAT11002 373 10 2.60E-02 0.4 368 4 5.91E-03 2 0.2 mATPOOO 404 88 1.48E-03 7.8 403 90 2.85E-03 4.1 1.9 mAT11004 356 97 1.47E-02 0.8 353 96 2.09E-02 0.6 1.4 mATPOB 398 105 1.46E-03 7.9 398 98 1.98E-03 5.8 1.4 mAT11008 341 112 1,ZZE-OZ 8.7 338 118 1.28E-03 9 1 mAT11010 432 157 3.90E-03 3 431 156 7.51E-03 1.5 1.9 Isotype control 430 4 N/S N/S 427 9 N/S N/S N/S

Table 36

Binding of SARS-COV-2-S RBD-MMH to anti-SARS-CoV-2 monoclonal antibodies in PBS-T buffer pH 7.4 and dissociation in PBS-T buffer pH 7.4 and pH 5.0 at 37°C

Working buffer: PBS-T, pH 7.4 at 37 °C. Working buffer: PBS-T, transition to pH 5.0 at 37 °C Ratio1½ Captured mAb mAb uptake level (EO) Binding of 90 nM RBD.mmh (EO) kd (1/s) 1½ (min) mAb uptake level (EO) Binding of 90 nM RBD.mmh (EO) kd (1/s) 1½ (min) pH 7.4 / pH 5.0 mAT10913 427 69 4,ZOE-02 0.3 430 65 3.53E-02 0.3 0.8 mAT10914 388 69 9.41E-03 1.2 391 57 1.00E-02 1.2 1.1 mAT10915 319 84 7.43E-04 15.5 316 94 2.05E-03 5.6 2.8 mAT10932 432 133 6.60E-04 17.5 452 131 2.11E-03 5.5 3.2 mAT10933 360 124 7.85E-03 1.5 353 114 1D4E-02 1 1.5 mAT10934 341 107 1.74E-02 0.7 338 109 1.71E-02 0.7 1 mAT10935 407 76 2.78E-02 0.4 413 70 1.28E-02 0.9 0.5 mAT10936 381 124 5.29E-03 2.2 379 116 1.60E-02 0.7 3 mAT10937 330 94 2.09E-02 0.6 326 104 1.55E-02 0.7 0.7 mAT10924 385 111 5.69E-03 2 390 FROM 1.48E-02 0.8 2.6 mAT10938 407 95 1.05E-03 eleven 417 82 7.61E-03 1.5 7.2 mAT10940 343 119 1.08E-02 1.1 341 135 8.23E-03 1.4 0.8 mAT10941 398 129 1.65E-03 7 407 128 2.21E-03 5.2 1.3

- 145 044746

mAT!0920 383 79 2.47E-02 0.5 382 68 2.93E-02 0.4 1.2 mAT!0921 345 89 1.79E-03 6.5 345 100 5.46E-02 0.2 30.6 mAT10923 355 87 2.35E-02 0.5 357 90 2DZE-02 0.5 0.9 mAT!0939 410 90 9.48E-03 1.2 419 78 1D4E-02 1 1.2 mAT!0922 251 85 9.07E-03 1.3 240 102 8.08E-03 1.4 0.9 mAT!0930 377 50 1.92E-02 0.6 383 44 1.20E-02 1 0.6 mAT10982 389 79 9.90E-03 1.2 391 66 6.27E-03 1.8 0.6 mAT!0984 378 133 1.71E-03 6.8 378 140 2,ZZE-OZ 5 1.4 mAT10985 457 172 3.63E-03 3.2 471 170 3.36E-03 3.4 0.9 mAT!0986 413 155 6.29E-04 18.4 417 148 3.18E-03 3.6 5.1 mAT!0987 379 105 2.37E-02 0.5 377 115 8.80E-03 1.3 0.4 mAT10988 467 109 4.35E-02 0.3 492 103 6.98E-02 0.2 1.6 mAT!0989 382 126 9.32E-03 1.2 379 105 6.13E-03 1.9 0.7 mAT!0970 340 93 7.65E-03 1.5 341 102 6.02E-03 1.9 0.8 mAT!0971 350 125 9.44E-04 12.2 352 129 1.70E-03 6.8 1.8 mAT!0964 380 140 1.94E-03 6 379 132 3.02E-03 3.8 1.6 mAT!0965 290 65 8.66E-03 1.3 284 77 7.40E-03 1.6 0.9 mAT!0966 417 152 1.60E-03 7.2 422 151 1.25E-03 9.2 0.8 mAT!0967 372 118 2.98E-04 38.8 377 114 4.05E-04 28.5 1.4 mAT!0954 336 118 1.74E-03 6.6 335 132 5,ZZE-OZ 2.2 3.1 mAT10955 404 100 1.22E-02 0.9 416 96 1.85E-02 0.6 1.5 mAT!0956 452 114 1.25E-02 0.9 462 101 2D8E-02 0.5 1.7 mAT10957 388 136 5.80E-04 19.9 390 146 7.93E-04 14.6 1.4 mAT!0977 293 44 1.59E-02 0.7 287 46 4.81E-02 0.2 3 mAT!0969 340 72 1.86E-02 0.6 344 69 1,ZZE-02 0.9 0.7 mAT10996 408 35 4.69E-02 0.2 415 42 9.02E-02 0.1 1.9 mAT!0998 308 20 2.86E-02 0.4 311 21 2.32E-02 0.5 0.8 mAT11002 373 10 2.60E-02 0.4 371 1 7D5E-04 16.2 0 mATPOOO 404 88 1.48E-03 7.8 411 96 2.46E-03 4.7 1.7 mAT11004 356 97 1.47E-02 0.8 362 98 2.70E-02 0.4 1.8 mATPOB 398 105 1.46E-03 7.9 411 93 2.10E-03 5.5 1.4 mAT11008 341 112 1,ZZE-OZ 8.7 340 127 Ι,ΙΟΕ-03 10.5 0.8 matPOYU 432 157 3.90E-03 3 440 156 7D5E-03 1.6 1.8 Isotype control 430 4 n/s N/S 435 15 N/S N/S N/S

Example 19. Binding of antibodies against SARS-CoV-2-S to virus-like particles.

To investigate the ability of a panel of anti-SARS-CoV-2-S monoclonal antibodies to bind the SARS-CoV-2 spike glycoprotein, we developed an in vitro binding assay using vesicular stomatitis virus (VSV) spedotyped for the SARS-CoV-2 spike protein in a detection platform based on electrochemiluminescence (MSD).

Pseudotyped vesicular stomatitis virus (VSV) virus-like particles (VLPs) were generated from HEK293T cells to transiently express SARS-CoV-2 spike protein (accession number MN908947.3, amino acids 16-1211). In addition, VLPs expressing VSV alone were prepared as a negative binding control.

Experiments were performed according to the following procedure. The above VLPs from two

- 146 044746 sources were diluted in PBS, seeded into 96-well carbon electrode plates (MULTIARRAY high-bind plate, MSD) and incubated overnight at 4°C to ensure VLP adhesion. Nonspecific binding sites were blocked with 2% (w/v) BSA in PBS for 1 h at room temperature (RT). Anti-SARS-CoV-2 antibodies and a non-binding control human IgG1 diluted in PBS + 0.5% BSA were added to the plate-bound particles at concentrations ranging from 0.0008 nM to 50 nM, buffer without antibodies was added in duplicate, and the plates were incubated. for 1 hour at room temperature with shaking. The plates were then washed with 1X PBS to remove unbound antibodies using an AquaMax2000 plate washer (MDS Analytical Technologies). Plate-bound antibodies were detected using anti-human IgG conjugated to SULFO-TAGTM (Jackson Immunoresearch) for 1 h at room temperature. After washing, the plates were developed using reading buffer (MSD) according to the procedure recommended by the manufacturer, and luminescence signals were recorded using a SECTOR Imager 600 (Meso Scale Development). Direct binding signals (in RLU) were recorded for VLPs expressing SARS-CoV-2 and VLPs containing only VSV.

The ability of anti-SARS-CoV-2-S monoclonal antibodies to bind to VLPs expressing SARS-CoV-2-S compared to binding to nonspecific VLPs expressing VSV was assessed using an immunobinding assay. Binding to immobilized VLPs on High Bind 96-well plates (MSD) was performed using a series of antibody dilutions, with bound antibodies detected using anti-human IgG conjugated to SULFO-TAGTM. Electrochemiluminescent binding signals were recorded on a Sector Imager 600 (MSD). RLU values were determined for antibody binding to VLPs. All antibodies showed concentration-dependent binding, and binding ratios of VLPs expressing SARS-COV-2-S and VLPs containing only VSV were analyzed at 5.5 nM and 0.20 nM.

Summary results of the binding of mAbs against SARS-CoV-2-S at two concentrations to VLPs expressing VSV/spike and VSV only are shown in Table. 37. 44 of 46 antibodies analyzed specifically bound to VSV/spike, with a VSV ratio of 3 or more at all concentrations. At 0.2 nM antibody, the VSV/spike to VSV ratio ranged from 3 to 56, and at 5 nM, from 3 to 303. Although two antibodies (mAb10998 and mAb11002) showed weak binding to VSV/Spike VLPs, when the ratio to VLP VSV less than 3, their signals at 5 nM were higher for VSV/spike than for VSV. The nonspecific isotype IgG1 antibody showed minimal binding, as expected.

Table 37

Binding specificity of anti-SARS-COV-2-S antibodies to VSV spike protein-expressing VLPs compared to VSV using electrochemiluminescence

Antibody binding signal (RLU) Ratio Antibody concentration 5.5 nm 0.20 nm 5.5 nm 0.20 nm No. mAb VSV/ Spike VSV VSV/ Spike VSV VSV/ Spike: VSV VSV/ Spike: VSV No. experiment mAT10913 1140 302 434 51 4 9 1 mAT10914 6139 1823 911 85 3 eleven 1 mAT10915 16763 702 2868 77 24 37 1 mAT10920 7757 2536 1332 102 3 13 3 mAT10921 8174 705 938 89 12 eleven 3 mAT10922 1458 129 562 39 eleven 6 2 mAT10923 1444 132 446 33 eleven 14 3 mAT10924 1922 353 375 57 5 7 1 mAT 10930 1488 291 429 38 5 4 2 mAT10932 11774 105 1282 35 113 37 1 mAT 10933 631 82 446 29 8 16 1 mAT10934 1099 124 648 29 9 22 1 mAT10935 2526 387 611 47 7 13 1 mAT10936 5087 228 1702 41 22 42 1 mAT10937 1056 204 374 43 5 9 1 mAT10938 11418 395 1223 37 29 33 1

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mAT10939 4656 637 948 99 7 10 3 mAT10940 947 58 384 34 16 And 1 mAT10941 7297 69 958 17 106 56 1 mAT10954 9727 205 2114 48 47 8 2 mAT10955 2189 270 397 55 8 6 2 mAT10956 1006 373 263 71 3 6 2 mAT10957 10624 127 1606 68 84 AND 2 mAT10964 14252 47 9486 26 303 24 2 mAT10965 1039 87 279 58 12 14 2 mAT10966 9176 97 1406 88 95 15 2 mAT10967 10744 122 1090 32 88 8 2 mAT10969 1163 334 262 42 3 6 3 mAT10970 5640 76 1061 50 74 13 2 mAT10971 7995 60 1372 27 134 20 2 mAT10977 26895 4283 9330 165 6 2 2 mAT10982 1875 220 427 36 9 6 2 mAT10984 9142 195 2270 33 47 9 2 mAT10985 1497 90 529 65 17 8 2 mAT10986 11155 177 2315 65 63 AND 2 mAT10987 1146 168 699 53 7 8 2 mAT10988 967 163 438 39 6 4 2 mAT10989 2195 128 1533 66 17 13 2 mAT10996 812 309 82 65 3 1 3 mAT10998 2253 1590 122 104 1 1 3 mAT11000 580 139 94 47 4 2 3 mAT11002 419 283 47 50 1 1 3 mAT11004 1061 56 386 28 19 14 3 mATPOB 26528 6299 7159 247 4 29 3 mAT11008 508 48 80 28 AND 3 3 μΑτΙΙΟΙΟ 349 64 96 thirty 5 3 3 Isotype control IgGl FROM 84 32 21 1 2 1 Isotypic IgGl control 167 127 75 35 1 2 3 Isotype control IgGl 94 99 99 31 1 1 2

Example 20. Binding of anti-SARS-CoV-2-S antibodies to cells expressing the spike protein.

To investigate the ability of a panel of anti-SARS-CoV-2-S monoclonal antibodies to bind cells expressing SARS-CoV-2-S, we developed an in vitro binding assay using cells expressing SARS-CoV-2-S on a detection platform based on electrochemiluminescence (MSD).

Inducible Jurkat/Tet3G/hCD20/Tet-3G cells were modified to transiently express the SARS-CoV-2 spike protein (accession number MN908947.3, amino acids 16-1211, Jurkat/Tet3G/hCD20/TetOn 3G Inducible SARS-CoV-2 Spike Protein High Sorted) and subjected to flow cytometric sorting to select cells with high levels of SARS-CoV-2 protein expression. Parental Jurkat/Tet3G/hCD20/Tet-3G cells were also included in the experiments as a negative binding control.

Experiments were performed according to the following procedure. Cells of the two lines described above were induced with 1 μg/ml doxycycline at 37°C for 36 hours before collection, centrifuged, washed with PBS, then diluted with PBS, seeded in 96-well carbon electrode plates (MULTI-ARRAY high-bind plate , MSD), and incubated overnight at 4°C to ensure cell adhesion. Nonspecific binding sites were blocked with 2% (w/v) BSA in PBS for

- 148 044746 hours at room temperature (RT). Anti-SARS-CoV-2 antibodies and a non-binding control human IgG1 diluted in PBS+0.5% BSA were added to the plate-bound cells at concentrations ranging from 0.0008 nM to 50 nM, buffer without antibodies was added in duplicate, and the plates were incubated. for one hour at room temperature with shaking. The plates were then washed with 1X PBS to remove unbound antibodies using an AquaMax2000 plate washer (MDS Analytical Technologies). Plate-bound antibodies were detected using SULFO-TAGTM-conjugated anti-human IgG (Jackson Immunoresearch) for one hour at room temperature. After washing, the plates were developed using reading buffer (MSD) according to the procedure recommended by the manufacturer, and luminescence signals were recorded using a SECTOR Imager 600 (Meso Scale Development). Direct binding signals (in RLU) were recorded for cells expressing SARS-CoV-2-S and a negative control cell line.

The ability of anti-SARS-CoV-2 monoclonal antibodies to bind to cells expressing the SARS-CoV-2 spike protein compared to binding to parent cells was assessed using an immunobinding assay. Binding to immobilized cells on High Bind 96-well plates (MSD) was performed using a series of antibody dilutions, with bound antibodies detected using anti-human IgG conjugated to SULFO-TAGTM. Electrochemiluminescent binding signals were recorded on a Sector Imager 600 (MSD). All antibodies showed concentration-dependent binding, and binding ratios of spike protein-expressing cells to parental cells were analyzed at 5.5 and 0.20 nM.

Summary results of the binding of anti-SARS-COV-2-S mAb at two concentrations to spike protein-expressing cells and parent Jurkat cells are shown in Table. 38. 44 of 46 antibodies analyzed specifically bound to Jurkat/spike cells (Jurkat/Tet3G/hCD20/Tet-On 3G Inducible SARS-CoV-2 Spike Protein High Sorted cells) with a ratio to parent cells of 4 or higher at any concentration . At a concentration of 0.2 nM, the ratio of binding signals to Jurkat/spike cells and parent cells ranged from 4 to 36, and at 5 nM, the ratio ranged from 4 to 63. Although two antibodies (mAb10998 and mAb11002) showed weak binding to Jurkat/spike cells spike with a parent cell binding ratio of less than 4, at 5 nM the binding signals were higher for Jurket/spike than for parent cells. The nonspecific isotype IgG1 antibody showed minimal binding, as expected.

Table 38

Binding specificity of anti-SARS-CoV-2-S antibodies to spike protein-expressing Jurkat cells compared to parental cells using electrochemiluminescence

Antibody binding signal (RLU) Ratio Concentration antibodies 5.5 nm 0.2 nm 5.5 nm 0.2 nm No. mAb Jurkat/ Spike Original Jurkat/ Spike Original Jurkat/Spike: original Jurkat/Spike: original mAT10913 907 174 576 36 5 16 mAT10914 1624 569 262 64 3 4 mAT10915 1814 217 269 42 8 6 mAT10920 3501 597 1970 80 6 25 mAT10921 3746 272 436 60 14 7 mAT10922 399 63 225 22 6 10 mAT10923 2561 103 1137 46 25 25 mAT10924 1418 121 336 24 12 14 mAT 10930 673 151 175 25 4 7 mAT10932 1525 65 206 29 23 7 mAT 10933 898 171 671 73 5 9 mAT10934 762 146 697 46 5 15

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mAT10935 1572 209 513 28 8 19 mAT10936 995 116 567 28 9 21 mAT10937 867 95 388 thirty 9 13 mAT10938 1678 165 195 thirty 10 7 mAT10939 3195 292 901 119 AND 8 mAT10940 657 51 291 19 13 16 mAT10941 1196 37 192 33 33 6 mAT10954 929 110 327 46 8 7 mAT10955 750 134 274 28 6 10 mAT10956 801 136 214 42 6 5 mAT10957 846 76 211 48 eleven 4 mAT10964 896 37 724 20 24 36 mAT10965 681 49 135 69 14 2 mAT10966 969 65 245 53 15 5 mAT10967 928 121 168 26 8 6 mAT10969 2793 124 774 35 23 22 mAT10970 743 59 246 57 13 4 mAT10971 839 42 263 23 20 12 mAT10977 2031 975 604 76 2 8 mAT10982 737 117 211 25 6 8 mAT10984 889 95 282 26 9 AND mAT10985 527 63 P 179 65 8 3 mAT10986 1050 92 341 33 AND 10 mAT10987 632 83 471 31 8 15 mAT10988 367 83 272 41 4 7 mAT 10989 778 62 778 38 13 20 mAT10996 1399 172 185 27 8 7 mAT10998 1277 393 128 65 3 2 mATPOOO 1745 70 261 22 25 12 mAT11002 241 160 thirty 36 2 1 mAT11004 2031 48 748 34 43 22 mATPOB 5052 1055 1044 70 5 15 mAT11008 2382 38 237 50 63 5 MATIOYU 387 52 140 33 8 4 Isotype control IgGl 95 34 62 22 3 3 Isotype control IgGl 58 65 21 48 1 0 Isotype control IgGl 64 73 118 62 1 2

All literature cited herein is incorporated herein by reference to the same extent as if each individual publication, database entry (e.g., Genbank sequences or GeneID entries), patent application, or patent had been expressly and separately cited to be incorporated by reference. It is intended by the present inventors that this incorporation by reference statement is intended to apply to each individual publication, database entry (e.g., Genbank sequences or GeneID entries), patent application, or patent, even if such reference is not directly adjacent to special statement of incorporation by reference. The inclusion in the description of specific incorporation statements, if any, does not in any way impair

- 150 044746 specified general statement of incorporation by reference. Citation of references herein is not intended as an admission that the reference is prior art, nor is it an admission of the content or date of those publications or documents.

Sequence listing <110> Regeneron Pharmaceuticals, Inc.

< 12 0> ANTIBODIES AND ANTIGEN-BINDING FRAGMENTS AGAINST SARS-COV-2 SPIKE GLYCOPROTEIN < 130> 10753WO01 < 160>850 < 170> PatentIn version 3.5 < 210>1 < 211>360 < 212> DNA < 213> Art natural sequence <220>

<223> Synthetic <400> 1

gaggtgcagc tggtggagtc tgggggaggc ttggtacagc ctggagggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagg aattatgaaa tgaactgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtttcatac attactagta gtggtagtac catgtactac 180 gcagactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240 ctgcaaatga acagcctgag agccgaggac acggctgttt attackgtgc gagagacggc 300 ttttactact actacgctat ggacgtctgg ggccaaggga ccacggtcac cgtctcctca 360

<210> 2 <211> 120 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>2

Glu Val Gln Leu Val Glu Ser Gly 15

Gly Gly Leu Val Gln Pro Gly Gly

1015

Ser Leu Arg Leu Ser Cys Ala Ala

Ser Gly Phe Thr Phe Arg Asn Tyr 25 30

Glu Met Asn Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Tyr Ile Thr Ser Ser Gly Ser

Thr Met Tyr Tyr Ala Asp Ser Val

- 151 044746

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Asn 70

Ala Lys Asn Ser Leu Tyr 75 80

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp 90

Thr Ala Val Tyr Tyr Cys 95

Ala Arg Asp Gly Phe

100

Tyr Tyr Tyr Tyr Ala

105

Met Asp Val Trp Gly Gln

110

Gly Thr Thr Val Thr Val Ser Ser

115120 <210>3 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>3 ggattcacct tcaggaatta tgaa <210>4 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>4

Gly Phe Thr Phe Arg Asn Tyr Glu <210>5 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>5 attactagta gtggtagtac catg <210>6 <211>8 <212> PROTEIN <213> Artificial sequence <220>

- 152 044746 < 223> Synthetic < 400>6

Ile Thr Ser Ser Gly Ser Thr Met 15 < 210>7 < 211>39 < 212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>7 gcgagagacg gcttttacta ctactacgct atggacgtc <210>8 <211>13 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>8

Ala Arg Asp Gly Phe Tyr Tyr Tyr Tyr Ala Met Asp Val

510 < 210>9 < 211>333 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic <400>9 cagtctgtgt tgacgcagcc gccctcagtg tctgcggccc caggacagaa ggtcaccatc60 tcctgctctg gaagcagctc caacattggg aataattatg tatcctggta ccagcagctc120 ccaggaacag cccccaaact cctcatttat gacaataata ag cgaccctc agggattcct180 gaccgattct ctggctccaa gtctggcacg tcagccaccc tgggcatcac cggactccag240 actggggacg aggccgatta ttactgcgga acatgggata gcagcctgag tgttggccga300 gtcttcggaa ctgggaccaa ggtcaccgtc cta333 <210 >10 <211>111 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic

- 153 044746 <400> 10

Gln Ser 1

Val Leu

Thr Gln 5

Pro Pro

Ser Val

Ser Ala

Ala Pro

Lys Val

Thr Ile

Ser Cys

Ser Gly

Ser Ser 25

Ser Asn

Ile Gly 30

Tyr Val

Ser Trp 35

Tyr Gln

Gln Leu

Pro Gly

Thr Ala

Pro Lys 45

Ile Tyr

Asp Asn

Asn Lys

Arg Pro 55

Ser Gly

Ile Pro

Asp Arg

Gly Ser 65

Lys Ser

Gly Thr 70

Ser Ala

Thr Leu

Gly Ile 75

Thr Gly

Thr Gly

Asp Glu

Ala Asp 85

Tyr Tyr

Cys Gly 90

Thr Trp

Asp Ser

Ser Val

Gly Arg

100

Val Phe

Gly Thr

Gly Thr 105

Lys Val

Thr Val

110

Gly Gln 15

Asn Asn

Leu Leu

Phe Ser

Leu Gln 80

Ser Leu 95

Leu <210> 11 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>11 agctccaaca ttgggaataa ttat <210>12 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>12

Ser Ser Asn Ile Gly Asn Asn Tyr <210>13 <211>9 <212> DNA <213> Artificial sequence <220>

- 154 044746 <223> Synthetic <400>13 gacaataat <210>14 <211>3 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>14

Asp Asn Asn < 210>15 < 211>36 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>15 ggaacatggg atagcagcct gagtgttggc cgagtc <210>16 <211>12 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>16

Gly Thr Trp Asp Ser Ser Leu Ser Val Gly Arg Val

510 <210>17 <211>1353 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 17

gaggtgcagc tggtggagtc tgggggaggc ttggtacagc ctggagggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagg aattatgaaa tgaactgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtttcatac attactagta gtggtagtac catgtactac 180 gcagactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240

- 155 044746

ctgcaaatga acagcctgag agccgaggac acggctgttt attackgtgc gagagacggc 300 ttttactact actacgctat ggacgtctgg ggccaaggga ccacggtcac cgtctcctca 360 gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacacc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcggggaga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtacacc tgcccccatc ccgggatgag 1080 ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140 gccgtggagt ggggagagcaa tggggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1260 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320 cagaagtccc tctccctgtc tccggggtaaa tga 1353

<210> 18 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 18

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Arg Asn Tyr 25 30

Glu Met Asn Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Tyr Ile Thr Ser Ser Gly Ser

55

Thr Met Tyr Tyr Ala Asp Ser Val 60

- 156 044746

Lys 65

Leu

Ala

Gly

Phe

Leu 145

Trp

Leu

Ser

Pro

Lys 225

Pro

Ser

Asp

Asn

Val

Gly Arg Phe

Gln Met Asn

Arg Asp Gly

100

Thr Thr Val

115

Pro Leu Ala 130

Gly Cys Leu

Asn Ser Gly

Gln Ser Ser

180

Ser Ser Leu

195

Ser Asn Thr 210

Thr His Thr

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Thr Ile Ser

Ser Leu Arg 85

Phe Tyr Tyr

Thr Val Ser

Pro Ser Ser

135

Val Lys Asp

150

Ala Leu Thr 165

Gly Leu Tyr

Gly Thr Gln

Lys Val Asp

215

Cys Pro Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

Arg Asp Asn

Ala Glu Asp

Tyr Tyr Ala

105

Ser Ala Ser 120

Lys Ser Thr

Tyr Phe Pro

Ser Gly Val

170

Ser Leu Ser

185

Thr Tyr Ile 200

Lys Lys Val

Cys Pro Ala

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Gln

Leu His Gln

Ala Lys Asn 75

Thr Ala Val

Met Asp Val

Thr Lys Gly

125

Ser Gly Gly

140

Glu Pro Val 155

His Thr Phe

Ser Val Val

Cys Asn Val

205

Glu Pro Lys

220

Pro Glu Leu 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu

Ser Leu Tyr

Tyr Tyr Cys 95

Trp Gly Gln 110

Pro Ser Val

Thr Ala Ala

Thr Val Ser

160

Pro Ala Val

175

Thr Val Pro 190

Asn His Lys

Ser Cys Asp

Leu Gly Gly

240

Leu Met Ile

255

Ser His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

- 157 044746

305

310

315

320

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

325 330335

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

340 345350

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

355 360365

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

370 375380

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

385 390 395400

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

405 410415

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

420 425430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440445

Gly Lys

450 <210>19 <211>654 <212> DNA <213> Artificial sequence

Synthetic <220> <223>

<400>

cagtctgtgt tcctgctctg ccaggaacag gaccgattct actggggacg gtcttcggaa accctgttcc atctccgact tgacgcagcc gaagcagctc cccccaaact ctggctccaa aggccgatta ctgggaccaa ccccctcctc tctaccccgg gccctcagtg caacattggg cctcatttat gtctgg cacg ttactgcgga ggtcaccgtc cgaggagctg cgccgtgacc tctgcggccc aataattatg gacaataata tcagccaccc acatgggata ctaggccagc caggccaaca gtggcctgga caggacagaa tatcctggta agcgaccctc tgggcatcac gcagcctgag ccaaggccgc aggccaccct aggcc gactc ggtcaccatc ccagcagctc agggattcct cggactccag tgttggccga cccctccgtg ggtgtgcctg ctcccccgtg

120

180

240

300

360

420

480

- 158 044746 aaggccggcg tcctacctgt acccacgagg tggagaccac ccctgacccc gctccaccgt caccccctcc cgagcagtgg ggagaagacc aagcagtcca aagtcccacc gtggccccca acaacaagta ggtcctactc ccgagtgctc cgccgcctcc ctgccaggtg ctga

540

600

654 <210> 20 <211> 217 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 20

Gln Ser 1

Val Leu

Thr Gln 5

Pro Pro

Ser Val

Ser Ala

Ala Pro

Lys Val

Thr Ile

Ser Cys

Ser Gly

Ser Ser 25

Ser Asn

Ile Gly 30

Tyr Val

Ser Trp 35

Tyr Gln

Gln Leu

Pro Gly

Thr Ala

Pro Lys 45

Ile Tyr

Asp Asn

Asn Lys

Arg Pro 55

Ser Gly

Ile Pro

Asp Arg

Gly Gln 15

Asn Asn

Leu Leu

Phe Ser

Gly Ser 65

Lys Ser

Gly Thr

Ser Ala

Thr Leu

Gly Ile 75

Thr Gly

Leu Gln

Thr Gly

Asp Glu

Ala Asp 85

Tyr Tyr

Cys Gly 90

Thr Trp

Asp Ser

Ser Leu 95

Ser Val

Gly Arg

100

Val Phe

Gly Thr

Gly Thr 105

Lys Val

Thr Val

110

Leu Gly

Glin Pro

Lys Ala 115

Ala Pro

Ser Val

120

Thr Leu

Phe Pro

Pro Ser 125

Ser Glu

Glu Leu

130

Gln Ala

Asn Lys

Ala Thr 135

Tyr Pro 145

Gly Ala

Val Thr

150

Val Ala

Lys Ala

Gly Val

Glu Thr 165

Thr Thr

Tyr Ala

Ala Ser

Ser Tyr

Leu Ser

Leu Val

Trp Lys

Pro Ser

170

Leu Thr

Cys Leu

140

Ile Ser

Asp Phe

Ala Asp 155

Lys Gln

Pro Glu

Ser Ser

Ser Asn

Gln Trp

Pro Val

160

Asn Lys 175

Lys Ser

- 159 044746

180 185190

His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu

195 200205

Lys Thr Val Ala Pro Thr Glu Cys Ser

210215 <210>21 <211>348 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 21 gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca ggatactttg tggtggagtc cctctgggtt ggctggagtg agggccgatt gcctgagacc actactgggg tggaggaggc caccgtcagt ggtctcagtt caccatctcc tga ggacacg ccagggaacc ttggtccagc agcaactaca atttatagcg agacacaatt gccgtgtatt ctggtcaccg ctggggggtc tgaactgggt gtggcagcac ccaagaacac actgtgcgag tctcctca cctgagactc ccgccaggct attctacgca gctgtatctt agatctgggg

120

180

240

300

348 <210> 22 <211> 116 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>22

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn 20 2530

Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

- 160 044746

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

Arg Asp Leu Gly Gly Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser

115 <210>23 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>23 gggttcaccg tcagtagcaa ctac <210>24 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>24

Gly Phe Thr Val Ser Ser Asn Tyr <210>25 <211>21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>25 atttatagcg gtggcagcac a <210>26 <211>7 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 26

Ile Tyr Ser Gly Gly Ser Thr

5

- 161 044746 <210> 27 <211> 30 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic <400>27 gcgagagatc tggggggata ctttgactac <210>28 <211>10 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>28

Ala Arg Asp Leu Gly Gly Tyr Phe Asp Tyr

510 < 210 > 29 < 211 > 318 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic <400> 29

gacatccaga tgaccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggccagtca gagttttagt agctggttgg cctggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctataag gcgtctagtt tagagagtgg ggtcccatca 180 aggttcagcg gcagtggatc tggacagaa ttcactctca ccatcagcag cctgcagcct 240 gatgattttg caacttatta ctgccaacag tataatagtt attacacttt tggccagggg 300

accaagctgg agatcaaa 318 < 210>30 < 211>106 < 212> PROTEIN < 213> Artificial sequence < 220>

<223> Synthetic <400> 30

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

5 10 15

- 162 044746

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Phe Ser Ser Trp 20 2530

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Tyr Thr 85 9095

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100105 <210>31 <211>18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>31 cagagtttta gtagctgg18 <210>32 <211>6 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>32

Gln Ser Phe Ser Ser Trp < 210>33 < 211>9 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400> 33 aaggcgtct <210> 34

- 163 044746 <211> 3 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>34

Lys Ala Ser <210>35 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>35 caacagtata atagttatta cact24 <210>36 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>36

Gln Gln Tyr Asn Ser Tyr Tyr Thr 15 <210>37 <211>1341 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 37

gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt caccgtcagt agcaactaca tgaactgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggcagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagacc tgaggacacg gccgtgtatt actgtgcgag agatctgggg 300 ggatactttg actactgggg ccagggaacc ctggtcaccg tctcctcagc ctccaccaag 360 ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctgggggg cacagcggcc 420 ctggggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 480

- 164 044746

gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 540 ctcagcagcg tggtgaccgt gccctccagc agcttggggca cccagaccta catctgcaac 600 gtgaatcaca agccagcaa caccaaggtg gacaagaaag ttgagcccaa atcttgtgac 660 aaaactcaca catgcccacc gtgccagca cctgaactcc tggggggacc gtcagtcttc 720 ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc 780 gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc 840 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cagtaccgt 900 gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc 960 aaggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg 1020 cagccccgag aaccacaggt gtacaccctg ccccatccc gggatgagct gaccaagaac 1080 caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg 1140 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1200 ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1260 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagtccctc 1320 tccctgtctc cggggtaaatg a 1341

<210> 38 <211> 446 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>38

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn 20 2530

Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala

- 165 044746

Arg

Thr

Pro

Val 145

Ala

Gly

Gly

Lys

Cys 225

Leu

Glu

Lys

Lys

Leu 305

Lys

Asp Leu Gly

100

Val Ser Ser

115

Ser Ser Lys 130

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Gln Thr

195

Val Asp Lys 210

Pro Pro Cys

Phe Pro Pro

Val Thr Cys

260

Phe Asn Trp

275

Pro Arg Glu 290

Thr Val Leu

Val Ser Asn

Gly Tyr Phe

Asp Tyr Trp

105

Gly Gln Gly

Thr Leu Val 110

Ala Ser Thr

Lys Gly Pro 120

Ser Val Phe

125

Pro Leu Ala

Ser Thr Ser

135

Gly Gly Thr

Ala Ala Leu

140

Gly Cys Leu

Phe Pro Glu

150

Pro Val Thr

Val Ser Trp 155

Asn Ser Gly

160

Gly Val His 165

Thr Phe Pro

170

Ala Val Leu

Gln Ser Ser

175

Leu Ser Ser

Tyr Ile Cys

Lys Val Glu

215

Pro Ala Pro

230

Lys Pro Lys 245

Val Val Val

Tyr Val Asp

Glu Gln Tyr

295

His Gln Asp

310

Lys Ala Leu 325

Val Val Thr

185

Asn Val Asn 200

Pro Lys Ser

Glu Leu Leu

Asp Thr Leu

250

Asp Val Ser

265

Gly Val Glu 280

Asn Ser Thr

Trp Leu Asn

Pro Ala Pro

330

Val Pro Ser

His Lys Pro

205

Cys Asp Lys

220

Gly Gly Pro 235

Met Ile Ser

His Glu Asp

Val His Asn

285

Tyr Arg Val

300

Gly Lys Glu 315

Ile Glu Lys

Ser Ser Leu 190

Ser Asn Thr

Thr His Thr

Ser Val Phe

240

Arg Thr Pro

255

Pro Glu Val 270

Ala Lys Thr

Val Ser Val

Tyr Lys Cys

320

Thr Ile Ser

335

- 166 044746

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345350

Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375380

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

385 390 395400

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

405 410415

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440445 <210>39 <211>642 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 39

gacatccaga tgaccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggccagtca gagttttagt agctggttgg cctggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctataag gcgtctagtt tagagagtgg ggtcccatca 180 aggttcagcg gcagtggatc tggacagaa ttcactctca ccatcagcag cctgcagcct 240 gatgattttg caacttatta ctgccaacag tataatagtt attacacttt tggccagggg 300 accaagctgg agatcaaacg aactgtggct gcaccatctg tcttcatctt cccgccactct 360 gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420 agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480 agtgtcacag agcaggacag caagcacagc acctacagcc tcagcagcac cctgacgctg 540 agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcacca tcaggggcctg 600 agctcgcccg tcacaaagag cttcaacagg gggagagtgtt ag 642

<210>40 <211>213 <212> PROTEIN

- 167 044746 <213> Artificial sequence <220>

<223> Synthetic <400> 40

Asp Ile Gln Met 1

Thr Gln Ser Pro 5

Ser Thr Leu Ser

Ala Ser Val Gly 15

Asp Arg Val Thr 20

Ile Thr Cys Arg

Ala Ser Gln Ser 25

Phe Ser Ser Trp 30

Leu Ala Trp Tyr

Gln Gln Lys Pro 40

Gly Lys Ala Pro

Lys Leu Leu Ile 45

Tyr Lys Ala Ser 50

Ser Leu Glu Ser

Gly Val Pro Ser 60

Arg Phe Ser Gly

Ser Gly Ser Gly 65

Thr Glu Phe Thr

Leu Thr Ile Ser

Ser Leu Gln Pro

Asp Asp Phe Ala

Thr Tyr Tyr Cys 85

Gln Gln Tyr Asn 90

Ser Tyr Tyr Thr 95

Phe Gly Gln Gly

100

Thr Lys Leu Glu

Ile Lys Arg Thr 105

Val Ala Ala Pro

110

Ser Val Phe Ile

115

Phe Pro Pro Ser

120

Asp Glu Gln Leu

Lys Ser Gly Thr 125

Ala Ser Val Val

130

Cys Leu Leu Asn

135

Asn Phe Tyr Pro

140

Arg Glu Ala Lys

Val Gln Trp Lys 145

Val Asp Asn Ala

150

Leu Gln Ser Gly

155

Asn Ser Gln Glu

160

Ser Val Thr Glu

Gln Asp Ser Lys 165

Asp Ser Thr Tyr 170

Ser Leu Ser Ser

175

Thr Leu Thr Leu

180

Ser Lys Ala Asp

Tyr Glu Lys His 185

Lys Val Tyr Ala 190

Cys Glu Val Thr

195

His Gln Gly Leu

200

Ser Ser Pro Val

Thr Lys Ser Phe 205

Asn Arg Gly Glu Cys

210

- 168 044746 <210> 41 <211> 1341 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 41

gaggtgcagc tggtggagtc tgggggaggc ttggtacagc ctggagggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagg aattatgaaa tgaactgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtttcatac attactagta gtggtagtac catgtactac 180 gcagactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240 ctgcaaatga acagcctgag agccgaggac acggctgttt attackgtgc gagagacggc 300 ttttactact actacgctat ggacgtctgg ggccaaggga ccacggtcac cgtctcctca 360 gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 420 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacgaagacc 600 tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 660 aaatatggtc ccccatgccc accgtgccca gcaccaggcg gtggcggacc atcagtcttc 720 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 780 gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 840 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cagtaccgt 900 gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 960 aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1020 cagccccgag agccacaggt gtacaccctg ccccatccc aggaggat gaccaagaac 1080 caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1140 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1200 ggctccttct tcctctacag caggctcacc gtggacaaga gcaggtggca ggaggggaat 1260 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagtccctc 1320 tccctgtctc tgggtaaatg a 1341

<210> 42 <211> 446 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic

- 169 044746 <400> 42

Glu Val Gln Leu Val

5

Glu Ser Gly Gly Gly

Leu Val Gln Pro Gly

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Phe Thr Phe Arg Asn 30

Glu Met Asn Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Ser Tyr Ile Thr Ser 50

Ser Gly Ser Thr Met 55

Tyr Tyr Ala Asp Ser 60

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Asn 70

Ala Lys Asn Ser Leu 75

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Arg Asp Gly Phe

100

Tyr Tyr Tyr Tyr Ala

105

Met Asp Val Trp Gly

110

Gly Thr Thr Val Thr 115

Val Ser Ser Ala Ser

120

Thr Lys Gly Pro Ser

125

Phe Pro Leu Ala Pro

130

Cys Ser Arg Ser Thr

135

Ser Glu Ser Thr Ala

140

Leu Gly Cys Leu Val 145

Lys Asp Tyr Phe Pro 150

Glu Pro Val Thr Val 155

Trp Asn Ser Gly Ala

165

Leu Thr Ser Gly Val

170

His Thr Phe Pro Ala

175

Leu Gln Ser Ser Gly

180

Leu Tyr Ser Leu Ser

185

Ser Val Val Thr Val

190

Ser Ser Ser Leu Gly 195

Thr Lys Thr Tyr Thr 200

Cys Asn Val Asp His

205

Pro Ser Asn Thr Lys 210

Val Asp Lys Arg Val

215

Glu Ser Lys Tyr Gly 220

Pro Cys Pro Pro Cys 225

Pro Ala Pro Gly Gly 230

Gly Gly Pro Ser Val 235

Gly

Tyr

Val

Val

Tyr 80

Cys

Gln

Val

Ala

Ser 160

Val

Pro

Lys

Pro

Phe 240

- 170 044746

Leu Phe

Pro Pro

Glu Val

Thr Cys

260

Gln Phe

Asn Trp 275

Lys Pro

290

Arg Glu

Lys Pro 245

Val Val

Tyr Val

Glu Gln

Lys Asp

Val Asp

Asp Gly

280

Phe Asn 295

Thr Leu

250

Val Ser 265

Val Glu

Ser Thr

Met Ile

Gln Glu

Val His

Tyr Arg

300

Ser Arg

Asp Pro

270

Asn Ala 285

Val Val

Thr Pro 255

Glu Val

Lys Thr

Ser Val

Leu Thr 305

Val Leu

His Gln

310

Asp Trp

Leu Asn

Gly Lys 315

Glu Tyr

Lys Cys

320

Lys Val

Ser Asn

Lys Gly 325

Leu Pro

Ser Ser

330

Ile Glu

Lys Thr

Ile Ser

335

Lys Ala

Lys Gly

340

Glin Pro

Arg Glu

Pro Gln 345

Val Tyr

Thr Leu

350

Pro Pro

Ser Gln

Glu Glu 355

Met Thr

Lys Asn

360

Gln Val

Ser Leu

Thr Cys 365

Leu Val

Lys Gly

370

Phe Tyr

Pro Ser

Asp Ile 375

Ala Val

Glu Trp

380

Glu Ser

Asn Gly

Gln Pro 385

Glu Asn

Asn Tyr

390

Lys Thr

Thr Pro

Pro Val 395

Leu Asp

Ser Asp

400

Gly Ser

Phe Phe

Leu Tyr 405

Ser Arg

Leu Thr

410

Val Asp

Lys Ser

Arg Trp 415

Gln Glu

Gly Asn

420

Val Phe

Ser Cys

Ser Val

425

Met His

Glu Ala

430

Leu His

Asn His

Tyr Thr 435

Gln Lys

Ser Leu

440

Ser Leu

Ser Leu

Gly Lys 445 <210> 43 <211> 351 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 43 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc

- 171 044746

tcctgtgcag cctctggggtt aatagtcagt cgcaactaca tgatctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtatatt actgtgcgag agatctggggt 300 acaggaggta tggacgtctg gggccaaggg accacggtca ccgtctcctc a 351

<210> 44 <211> 117 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 44

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Leu Ile Val Ser Arg Asn 25 30

Tyr Met Ile Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Ser Gly Gly Ser

55

Thr Phe Tyr Ala Asp Ser Val Lys 60

Gly Arg Phe Thr Ile Ser Arg His 65 70

Asn Ser Lys Asn Thr Leu Tyr Leu

80

Gln Met Asn Ser Leu Arg Ala Glu 85

Asp Thr Ala Val Tyr Tyr Cys Ala

95

Arg Asp Leu Gly Thr Gly Gly Met

100

Asp Val Trp Gly Gln Gly Thr Thr

105 110

Val Thr Val Ser Ser

115 <210> 45 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 45 gggttaatag tcagtcgcaa ctac

- 172 044746 <210> 46 <211> 8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>46

Gly Leu Ile Val Ser Arg Asn Tyr < 210>47 < 211>21 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>47 atttatagcg gtggtagcac a21 <210>48 <211>33 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>48 gcgagagatc tgggtacagg aggtatggac gtc <210>49 <211>11 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>49

Ala Arg Asp Leu Gly Thr Gly Gly Met Asp Val

510 < 210> 50 < 211> 321 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400> 50

- 173 044746

gacatccagt tgaccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgct gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120 gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180 aggttcagcg gcagtggatc tggacagaa ttcactctca caatcagcag cctgcagcct 240 gaagatttg caacttatta ctgtcaacag cttaatagtt accctctcac tttcggcgga 300 gggaccaagg tggagatcaa a 321

<210> 51 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>51

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

5 1015

Asp Arg Val Thr Ile Thr Cys Trp Ala Ser Gln Gly Ile Ser Ser Tyr 20 2530

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100105 <210>52 <211>18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 52 cagggcatta gcagttat

- 174 044746 <210> 53 <211> 6 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>53

Gln Gly Ile Ser Ser Tyr < 210>54 < 211>9 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>54 gctgcatcc <210>55 <211>3 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>55

Ala Ala Ser <210>56 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>56 caacagctta atagttaccc tctcact <210>57 <211>9 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 57

Gln Gln Leu Asn Ser Tyr Pro Leu Thr

- 175 044746 <210> 58 <211> 1332 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>58 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc60 tcctgtgcag cctctgggtt aatagtcagt cgcaactaca tgatctgggt ccgccaggct120 ccagggaagg ggctggagtg ggtctca gtt atttatagcg gtggtagcac attctacgca180 gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt240 caaatgaaca gcctgagagc tgaggacacg gccgtatatt actgtgcgag agatctgggt300 acaggaggta tggacgtctg gggccaaggg accac ggtca ccgtctcctc agcctccacc360 aagggcccat cggtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctac acctgc600 aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt660 cccccatgcc caccgtgccc agcaccaggc ggtggcggac catcagtctt cctgttcccc720 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtgg tggtg780 gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg840 cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc900 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc960 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga1020 gagccacagg tgtacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc1080 ctgacctgcc tggtcaaagg ct tctacccc agcgacatcg ccgtggagtg ggagagcaat1140 gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc1200 ttcctctaca gcaggctcac cgtggacaag agcaggtggc aggaggggaa tgtcttctca1260 tgctccgtga tg catgaggc tctgcacaac cactacacac agaagtccct ctccctgtct 1320 ctgggtaaat ga1332 <210>

<211>

<212>

<213>

443

PROTEIN

Artificial sequence

- 176 044746 <220>

<223> Synthetic <400> 59

Glu Val Gln Leu Val 1 5

Glu Ser Gly Gly Gly 10

Leu Val Gln Pro Gly

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Leu Ile Val Ser Arg 30

Tyr Met Ile Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Ser Val Ile Tyr Ser 50

Gly Gly Ser Thr Phe 55

Tyr Ala Asp Ser Val 60

Gly Arg Phe Thr Ile 65

Ser Arg His Asn Ser 70

Lys Asn Thr Leu Tyr 75

Gln Met Asn Ser Leu

Arg Ala Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Asp Leu Gly Thr

100

Gly Gly Met Asp Val

105

Trp Gly Gln Gly Thr

110

Val Thr Val Ser Ser

115

Ala Ser Thr Lys Gly 120

Pro Ser Val Phe Pro

125

Ala Pro Cys Ser Arg 130

Ser Thr Ser Glu Ser

135

Thr Ala Ala Leu Gly 140

Leu Val Lys Asp Tyr 145

Phe Pro Glu Pro Val 150

Thr Val Ser Trp Asn 155

Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe

170

Pro Ala Val Leu Gln

175

Ser Gly Leu Tyr Ser

180

Leu Ser Ser Val Val

185

Thr Val Pro Ser Ser

190

Leu Gly Thr Lys Thr

195

Tyr Thr Cys Asn Val

200

Asp His Lys Pro Ser 205

Thr Lys Val Asp Lys

210

Arg Val Glu Ser Lys

215

Tyr Gly Pro Pro Cys

220

Gly

Asn

Val

Lys

Leu 80

Ala

Thr

Leu

Cys

Ser 160

Ser

Ser

Asn

Pro

Pro

Pro Cys Pro Ala Pro

Gly Gly Gly Gly Pro

Ser Val Phe Leu Phe

- 177 044746

225

230

235

Pro Lys Pro Lys Asp

245

Thr Leu Met Ile Ser

250

Arg Thr Pro Glu Val

255

Cys Val Val Val Asp

260

Val Ser Gln Glu Asp

265

Pro Glu Val Gln Phe

270

Trp Tyr Val Asp Gly

275

Val Glu Val His Asn

280

Ala Lys Thr Lys Pro

285

Glu Glu Gln Phe Asn

290

Ser Thr Tyr Arg Val

295

Val Ser Val Leu Thr

300

Leu His Gln Asp Trp 305

Leu Asn Gly Lys Glu 310

Tyr Lys Cys Lys Val 315

Asn Lys Gly Leu Pro

325

Ser Ser Ile Glu Lys

330

Thr Ile Ser Lys Ala

335

Gly Gln Pro Arg Glu

340

Pro Gln Val Tyr Thr

345

Leu Pro Pro Ser Gln

350

Glu Met Thr Lys Asn

355

Gln Val Ser Leu Thr

360

Cys Leu Val Lys Gly

365

Tyr Pro Ser Asp Ile

370

Ala Val Glu Trp Glu

375

Ser Asn Gly Gln Pro

380

Asn Asn Tyr Lys Thr 385

Thr Pro Pro Val Leu 390

Asp Ser Asp Gly Ser 395

Phe Leu Tyr Ser Arg

405

Leu Thr Val Asp Lys

410

Ser Arg Trp Gln Glu

415

Asn Val Phe Ser Cys

420

Ser Val Met His Glu

425

Ala Leu His Asn His

430

240

Thr

Asn

Arg

Val

Ser 320

Lys

Glu

Phe

Glu

Phe 400

Gly

Tyr

Thr Gln Lys Ser Leu 435

Ser Leu Ser Leu Gly 440

Lys <210> 60 <211> 645 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic

- 178 044746

<400> 60 gacatccagt tgaccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgct gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120 gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180 aggttcagcg gcagtggatc tggacagaa ttcactctca caatcagcag cctgcagcct 240 gaagatttg caacttatta ctgtcaacag cttaatagtt accctctcac tttcggcgga 300 gggaccaagg tggagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcaggggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 645

<210> 61 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>61

Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly 1 5 1015

Asp Arg Val Thr Ile Thr Cys Trp Ala Ser Gln Gly Ile Ser Ser Tyr 20 2530

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105110

Pro Ser Val Phe Ile Phe Pro Pro

Ser Asp Glu Gln Leu Lys Ser Gly

- 179 044746

115

120

125

Thr Ala Ser Val Val Cys Leu Leu

130 135

Asn Asn Phe Tyr Pro Arg Glu Ala

140

Lys Val Gln Trp Lys Val Asp Asn

145 150

Ala Leu Gln Ser Gly Asn Ser Gln

155 160

Glu Ser Val Thr Glu Gln Asp Ser

165

Lys Asp Ser Thr Tyr Ser Leu Ser

170 175

Ser Thr Leu Thr Leu Ser Lys Ala 180

Asp Tyr Glu Lys His Lys Val Tyr

185 190

Ala Cys Glu Val Thr His Gln Gly

195 200

Leu Ser Ser Pro Val Thr Lys Ser

205

Phe Asn Arg Gly Glu Cys

210

<210> 62 <211> 1329 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400>62 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt caccgtcagt agcaactaca tgaactgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggcagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagacc tgaggacacg gccgtgtatt actgtgcgag agatctgggg 300 ggatactttg actactgggg ccagggaacc ctggtcaccg tctcctcagc ctccaccaag 360 ggcccatcgg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 420 ctggggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 480 gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 540 ctcagcagcg tggtgaccgt gccctccagc agcttggggca cgaagaccta cacctgcaac 600 gtagatcaca agccagcaa caccaaggtg gacaagag ttgagtccaa atatggtccc 660 ccatgcccac cgtgcccagc accaggcggt ggcggaccat cagtcttcct gttcccccca 720 aaacccaagg acactctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 780 gtgagccagg aagaccccga ggtccagttc aactggtacg tggatggcgt ggaggtgcat 840

- 180 044746 aatgccaaga ctcaccgtcc aaaggcctcc ccacaggtgt acctgcctgg cagccggaga ctctacagca tccgtgatgc ggtaaatga caaagccgcg tgcaccagga cgtcctccat acaccctgcc tcaaaggctt acaactacaa ggctcaccgt atgaggctct gga ggagcag ctggctgaac cgagaaaacc cccatcccag ctaccccagc gaccacgcct ggacaagagc gcacaaccac ttcaacagca ggcaaggagt atctccaaag gaggagatga gacatcgccg cccgtgctgg aggtggcagg tacacacaga cgtaccgtgt acaagtgcaa ccaaagggca ccaagaacca tggag tggga actccgacgg aggggaatgt agtccctctc ggtcagcgtc ggtctccaac gccccgagag ggtcagcctg gagcaatggg ctccttcttc cttctcatgc cctgtctctg

900

960

1020

1080

1140

1200

1260

1320

1329 <210> 63 <211> 442 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 63

Glu Val 1

Gln Leu

Val Glu 5

Ser Leu

Arg Leu 20

Ser Cys

Tyr Met

Asn Trp 35

Val Arg

Ser Val

Ile Tyr

Ser Gly

Gly Arg 65

Phe Thr

Ile Ser

Gln Met

Asn Ser

Leu Arg 85

Arg Asp

Leu Gly

100

Gly Tyr

Thr Val

Ser Ser 115

Ala Ser

Pro Cys

Ser Arg

Ser Thr

Ser Gly

Ala Ala

Gln Ala 40

Gly Ser 55

Arg His

Pro Glu

Phe Asp

Thr Lys

120

Ser Glu

Gly Gly 10

Ser Gly 25

Pro Gly

Thr Phe

Asn Ser

Asp Thr

Tyr Trp 105

Gly Pro

Ser Thr

Leu Val

Phe Thr

Lys Gly

Tyr Ala 60

Lys Asn 75

Ala Val

Gly Gln

Ser Val

Ala Ala

Glin Pro

Val Ser

Leu Glu 45

Asp Ser

Gly Gly 15

Ser Asn

Trp Val

Val Lys

Thr Leu

Tyr Tyr

Gly Thr

110

Phe Pro 125

Leu Gly

Tyr Leu 80

Cys Ala 95

Leu Val

Leu Ala

Cys Leu

- 181 044746

130

135

140

Val 145

Ala

Gly

Gly

Lys

Cys 225

Lys

Val

Tyr

Glu

His 305

Lys

Gln

Met

Pro

Lys Asp Tyr

Leu Thr Ser

Leu Tyr Ser

180

Thr Lys Thr

195

Val Asp Lys 210

Pro Ala Pro

Pro Lys Asp

Val Val Asp

260

Val Asp Gly

275

Gln Phe Asn 290

Gln Asp Trp

Gly Leu Pro

Pro Arg Glu

340

Thr Lys Asn

355

Ser Asp Ile 370

Phe Pro Glu

150

Pro Val Thr

Val Ser Trp 155

Asn Ser Gly

160

Gly Val His 165

Thr Phe Pro

170

Ala Val Leu

Gln Ser Ser

175

Leu Ser Ser

Tyr Thr Cys

Arg Val Glu

215

Gly Gly Gly

230

Thr Leu Met 245

Val Ser Gln

Val Glu Val

Ser Thr Tyr

295

Leu Asn Gly

310

Ser Ser Ile 325

Pro Gln Val

Gln Val Ser

Ala Val Glu

375

Val Val Thr

185

Asn Val Asp 200

Ser Lys Tyr

Gly Pro Ser

Ile Ser Arg

250

Glu Asp Pro

265

His Asn Ala 280

Arg Val Val

Lys Glu Tyr

Glu Lys Thr

330

Tyr Thr Leu

345

Leu Thr Cys 360

Trp Glu Ser

Val Pro Ser

His Lys Pro

205

Gly Pro Pro

220

Val Phe Leu 235

Thr Pro Glu

Glu Val Gln

Lys Thr Lys

285

Ser Val Leu

300

Lys Cys Lys 315

Ile Ser Lys

Pro Pro Ser

Leu Val Lys

365

Asn Gly Gln

380

Ser Ser Leu 190

Ser Asn Thr

Cys Pro Pro

Phe Pro Pro

240

Val Thr Cys

255

Phe Asn Trp 270

Pro Arg Glu

Thr Val Leu

Val Ser Asn

320

Ala Lys Gly

335

Gln Glu Glu 350

Gly Phe Tyr

Pro Glu Asn

- 182 044746

Asn

385

Tyr

Lys

Thr

Thr

Pro

390

Pro

Val

Leu

Asp

Ser

395

Asp

Gly

Ser

Phe

Phe

400

Leu

Tyr

Ser

Arg

Leu

405

Thr

Val

Asp

Lys

Ser

410

Arg

Trp

Gln

Glu

Gly 415

Asn

Val

Phe

Ser

Cys 420

Ser

Val

Met

His

Glu

425

Ala

Leu

His

Asn

His

430

Tyr

Thr

Gln

Lys

Ser

435

Leu

Ser

Leu

Ser

Leu

440

Gly

Lys <210> 64 <211> 360 <212> DNA <213> Artificial sequence

Synthetic <220>

<223>

<400>

caggtgcagc tcctgtgcag ccaggcaagg gcagactccg ctgcaaatga ccgggctact tggtggagtc cgtctggatt ggctggagtg tgaagggccg acagcctgag actacggtat tgggggaggc caccttcagt ggtggcagtt attcaccatc agccgaggac ggacgtctgg gtggtcca gc tactatggca atatggtatg tccagagaca acggctgtgt ggccaaggga ctgggaggtc tgcactgggt atggaagtaa attccaagaa attactgtgc ccacggtcac cctgagactc ccgccaggct taaattctat cacgctgtat ggcagctcgg cgtctcctca

120

180

240

300

360 <210> 65 <211> 120 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 65

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala

Ser Gly Phe Thr Phe Ser Tyr Tyr 25 30

Gly Met His Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ala Val Ile Trp Tyr Asp Gly Ser

55

Asn Lys Phe Tyr Ala Asp Ser Val 60

- 183 044746

Lys 65 Gly Arg Phe Thr Ile 70 Ser Arg Asp Asn Ser 75 Lys Asn Thr Leu Tyr 80 Leu Gln Met Asn Ser 85 Leu Arg Ala Glu Asp 90 Thr Ala Val Tyr Tyr 95 Cys Ala Ala Ala Arg 100 Pro Gly Tyr Tyr Tyr 105 Gly Met Asp Val Trp 110 Gly Gln Gly Thr Thr 115 Val Thr Val Ser Ser 120

<210> 66 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>66 ggattcacct tcagttacta tggc <210>67 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>67

Gly Phe Thr Phe Ser Tyr Tyr Gly <210>68 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>68 atatggtatg atggaagtaa taaa <210>69 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic

- 184 044746 <400>69

Ile Trp Tyr Asp Gly Ser Asn Lys 15 <210>70 <211>39 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>70 gcggcagctc ggccgggcta ctactacggt atggacgtc <210>71 <211>13 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>71

Ala Ala Ala Arg Pro Gly Tyr Tyr Tyr Gly Met Asp Val 1 510 <210>72 <211>321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 72 gacatccaga tgacccagtc tccatcctca ctgtctgctt ctgtaggaga cagagtcacc atcacttgtc gggcgagtca gggcattagc aattatttag cctggtttca gcagaaacca gggaaagccc ctaattccct gatctatgct gcatccagtt tgcaacgtgg ggtcccatca aagttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct gaagattttg caacttatta ctgccaacag tataatagtt accctcggac gttcggccaa gggaccaagg tggaaatcaa a

120

180

240

300

321 <210> 73 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 73

- 185 044746

Asp Ile Gln Met 1

Thr Gln Ser Pro 5

Ser Ser Leu Ser 10

Ala Ser Val Gly 15

Asp Arg Val Thr 20

Ile Thr Cys Arg

Ala Ser Gln Gly 25

Ile Ser Asn Tyr 30

Leu Ala Trp Phe

Gln Gln Lys Pro 40

Gly Lys Ala Pro

Asn Ser Leu Ile 45

Tyr Ala Ala Ser 50

Ser Leu Gln Arg

Gly Val Pro Ser 60

Lys Phe Ser Gly

Ser Gly Ser Gly 65

Thr Asp Phe Thr 70

Leu Thr Ile Ser

Ser Leu Gln Pro

Glu Asp Phe Ala

Thr Tyr Tyr Cys 85

Gln Gln Tyr Asn 90

Ser Tyr Pro Arg 95

Thr Phe Gly Gln

100

Gly Thr Lys Val

Glu Ile Lys 105 <210> 74 <211> 18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>74 cagggcatta gcaattat <210>75 <211>6 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>75

Gln Gly Ile Ser Asn Tyr <210>76 <211>27 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic

- 186 044746 <400>76 caacagtata atagttaccc tcggacg <210>77 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>77

Gln Gln Tyr Asn Ser Tyr Pro Arg Thr 15 < 210>78 < 211>1353 < 212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 78 caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgtgcag cgtctggatt caccttcagt tactatggca tgcactgggt ccgccaggct 120 ccaggcaagg ggctggagtg ggtggcagtt atatggtatg atggaagtaa taaattctat 180 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaggac acggctgtgt attackgtgc ggcagctcgg 300 ccggggctact actacggtat ggacgtctgg ggccaaggga ccacggtcac cgtctcctca 360 gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacacc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcggggaga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtacacc tgcccccatc ccgggatgag 1080

- 187 044746 ctgaccaaga gccgtggagt ctggactccg cagcagggga cagaagtccc accaggtcag gggagagcaa acggctcctt acgtcttctc tctccctgtc cctgacctgc tgggcagccg cttcctctac atgctccgtg tccgggtaaa ctggtcaaag gagaacaact a gcaagctca atgcatgagg tga gcttctatcc acaagaccac ccgtggacaa ctctgcacaa cagcgacatc gcctcccgtg gagcaggtgg ccactacacg

1140

1200

1260

1320

1353 <210> 79 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 79

Gln Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly 10

Val Val

Glin Pro

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Phe Thr

Phe Ser

Gly Met

His Trp 35

Val Arg

Gln Ala

Pro Gly

Lys Gly

Leu Glu 45

Ala Val

Ile Trp

Tyr Asp

Gly Ser 55

Asn Lys

Phe Tyr 60

Ala Asp

Gly Arg 15

Tyr Tyr

Trp Val

Ser Val

Lys Gly 65

Arg Phe

Thr Ile

Ser Arg

Asp Asn

Ser Lys 75

Asn Thr

Leu Tyr 80

Leu Gln

Met Asn

Ser Leu 85

Arg Ala

Glu Asp 90

Thr Ala

Val Tyr

Tyr Cys 95

Ala Ala

Ala Arg

100

Pro Gly

Tyr Tyr

Tyr Gly 105

Met Asp

Val Trp

110

Gly Gln

Gly Thr

Thr Val 115

Thr Val

Ser Ser

120

Ala Ser

Thr Lys

Gly Pro 125

Ser Val

Phe Pro

130

Leu Ala

Pro Ser

Ser Lys 135

Ser Thr

Ser Gly

140

Gly Thr

Ala Ala

Leu Gly 145

Cys Leu

Val Lys

150

Asp Tyr

Phe Pro

Glu Pro 155

Val Thr

Val Ser

160

Trp Asn

Ser Gly

Ala Leu 165

Thr Ser

Gly Val

170

His Thr

Phe Pro

Ala Val 175

- 188 044746

Leu

Ser

Pro

Lys 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Lys

Gln Ser Ser

180

Gly Leu Tyr

Ser Leu Ser

185

Ser Val Val

Thr Val Pro 190

Ser Ser Leu

195

Ser Asn Thr 210

Thr His Thr

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Leu Val 370

Ser Asn Gly

Asp Ser Asp

Ser Arg Trp

Gly Thr Gln

Thr Tyr Ile 200

Cys Asn Val

205

Asn His Lys

Lys Val Asp

215

Cys Pro Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Asp

Lys Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe 405

Gln Gln Gly

Lys Lys Val

Glu Pro Lys

220

Ser Cys Asp

Cys Pro Ala

Pro Glu Leu 235

Leu Gly Gly

240

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Gln

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Leu Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

410

Asn Val Phe

Lys Asp Thr

Leu Met Ile

255

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Ser Cys Ser

Ser His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

415

Val Met His

- 189 044746

420

425

430

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

435 440445

Gly Lys

450 <210>80 <211>645 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 80 gacatccaga tgaccagtc tccatcctca ctgtctgctt ctgtaggaga cagagtcacc 60 atcacttgtc gggcgagtca gggcattagc aattatttag cctggtttca gcagaaacca 120 gggaaagccc ctaattccct gatctatgct gcatccagtt tgcaacgtgg ggtcccatca 180 aagttcagcg gcagtggatc tggacagat ttcactctca ccatcagcag cctgcagcct 240 gaagatttg caacttatta ctgccaacag tataatagtt accctcggac gttcggccaa 300 gggaccaagg tggaaatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcaggggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 645

<210> 81 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 81

Asp Ile Gln Met

Thr Gln Ser Pro Ser Ser Leu Ser Ala 5 10

Ser Val Gly

Asp Arg Val Thr

Ile Thr Cys Arg Ala Ser Gln Gly Ile 25

Ser Asn Tyr 30

Leu Ala Trp Phe

Gln Gln Lys Pro Gly Lys Ala Pro Asn 40 45

Ser Leu Ile

- 190 044746

Tyr Ala 50

Ser Gly 65

Glu Asp

Thr Phe

Pro Ser

Ala Ser

Ser Gly

Phe Ala

Gly Gln

100

Val Phe

115

Ser Leu

Thr Asp 70

Thr Tyr 85

Gly Thr

Gln Arg 55

Phe Thr

Tyr Cys

Lys Val

Gly Val

Leu Thr

Gln Gln

Glu Ile 105

Ile Phe

Pro Pro

120

Ser Asp

Thr Ala

130

Ser Val

Val Cys

Leu Leu 135

Asn Asn

Pro Ser

Ile Ser 75

Tyr Asn

Lys Arg

Glu Gln

Phe Tyr

140

Lys Phe

Ser Leu

Ser Tyr

Thr Val

110

Leu Lys 125

Pro Arg

Ser Gly

Glin Pro

Pro Arg 95

Ala Ala

Ser Gly

Glu Ala

Lys Val 145

Gln Trp

Lys Val

150

Asp Asn

Ala Leu

Gln Ser 155

Gly Asn

Ser Gln

160

Glu Ser

Val Thr

Glu Gln 165

Asp Ser

Lys Asp

170

Ser Thr

Tyr Ser

Leu Ser 175

Ser Thr

Leu Thr

180

Leu Ser

Lys Ala

Asp Tyr 185

Glu Lys

His Lys

190

Val Tyr

Ala Cys

Glu Val 195

Thr His

Gln Gly

200

Leu Ser

Ser Pro

Val Thr 205

Lys Ser

Phe Asn Arg Gly Glu Cys

210 <210> 82 <211> 351 <212> DNA <213> Artificial sequence

Synthetic <220>

<223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg gactccgtga tggtggagtc cctctgggat ggctggagtg agggccgatt tggaggaggc caccgtcagt ggtctcagtt caccatctcc ttggtccagc agcaactaca atttatagcg agacacaatt ctggggggtc tgagctgggt gtggtag cac ccaagaacac cctgagactc ccgccaggct attctacgca gctgtatctt

120

180

240

- 191 044746 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agaacgtaac

300

351 tttgatgctt ttgatatctg gggccaaggg acaatggtca ccgtctcttc a <210> 83 <211> 117 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 83

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Ile Thr Val Ser Ser Asn 25 30

Tyr Met Ser Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Ser Gly Gly Ser

55

Thr Phe Tyr Ala Asp Ser Val Lys 60

Gly Arg Phe Thr Ile Ser Arg His 65 70

Asn Ser Lys Asn Thr Leu Tyr Leu

80

Gln Met Asn Ser Leu Arg Ala Glu 85

Asp Thr Ala Val Tyr Tyr Cys Ala

95

Arg Glu Arg Asn Phe Asp Ala Phe

100

Asp Ile Trp Gly Gln Gly Thr Met

105 110

Val Thr Val Ser Ser

115 <210> 84 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>84 gggatcaccg tcagtagcaa ctac <210>85 <211>8 <212> PROTEIN <213> Artificial sequence

- 192 044746 <220>

<223>

Synthetic <400>

Gly Ile Thr Val Ser Ser Asn Tyr < 210> 86 < 211> 33 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>86 gcgagagaac gtaactttga tgcttttgat atc33 <210>87 <211>11 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>87

Ala Arg Glu Arg Asn Phe Asp Ala Phe Asp Ile

510 < 210 > 88 < 211 > 324 < 212 > DNA < 213 > Artificial sequence < 220 >

< 223> Synthetic < 400>88 gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc60 atcacttgtc gggcgagtca gggtattagc agctggttag cctggtatca gcagaaacca120 gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca180 aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct240 gaagattttg caacttacta ttgtcaacag gctaacagtt tccccctatt cactttcggc300 cctgggacca aagtggatat caaa324 <210> 89 < 211>108 < 212> PROTEIN < 213> Artificial sequence

- 193 044746 <220>

<223> Synthetic <400>89

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

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp 20 2530

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Pro Leu 85 9095

Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100105 <210>90 <211>18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>90 cagggtatta gcagctgg <210>91 <211>6 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>91

Gln Gly Ile Ser Ser Trp <210>92 <211>30 <212> DNA <213> Artificial sequence

- 194 044746 <220>

<223> Synthetic <400>92 caacaggcta acagtttccc cctattcact <210>93 <211>10 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>93

Gln Gln Ala Asn Ser Phe Pro Leu Phe Thr

510 <210>94 <211>1344 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 94 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctgggat caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agaacgtaac 300 tttgatgctt ttgatatctg gggccaaggg acaatggtca ccgtctcttc agcctccacc 360 aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc 600 aacgtgaatc acaagcccag caacaccaag gtggacaaga aagttgagcc caaatcttgt 660 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 720 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 780 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 840 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 900 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 960

- 195 044746

tgcaaggtct ccaacaaagc cctcccagcc ccatcgaga aaaccatctc caaagccaaa 1020 gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 1080 aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1140 tggggagagca atggggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1200 gacggctcct tcttcctcta cagcaagctc accgtggac agagcaggtg gcagcagggg 1260 aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagtcc 1320 ctctccctgt ctccgggtaa atga 1344

<210> 95 <211> 447 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 95

Glu Val Gln 1

Leu Val Glu Ser Gly Gly 5

Gly Leu Val Gln Pro 10

Ser Leu Arg

Leu Ser Cys Ala Ala Ser

25

Gly Ile Thr Val Ser 30

Gly Gly 15

Ser Asn

Tyr Met Ser

Trp Val Arg Gln Ala Pro 40

Gly Lys Gly Leu Glu 45

Trp Val

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

Arg Glu Arg Asn Phe Asp Ala Phe Asp Ile Trp Gly Gln Gly Thr Met

100 105110

Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu

115 120125

Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys

130 135140

Leu Val Lys Asp Tyr Phe Pro Glu

145 150

Pro Val Thr Val Ser Trp Asn Ser

155 160

- 196 044746

Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe

170

Pro Ala Val Leu Gln

175

Ser Gly Leu Tyr Ser

180

Leu Ser Ser Val Val

185

Thr Val Pro Ser Ser

190

Leu Gly Thr Gln Thr 195

Tyr Ile Cys Asn Val 200

Asn His Lys Pro Ser 205

Thr Lys Val Asp Lys

210

Lys Val Glu Pro Lys

215

Ser Cys Asp Lys Thr

220

Thr Cys Pro Pro Cys 225

Pro Ala Pro Glu Leu 230

Leu Gly Gly Pro Ser 235

Phe Leu Phe Pro Pro

245

Lys Pro Lys Asp Thr

250

Leu Met Ile Ser Arg

255

Pro Glu Val Thr Cys

260

Val Val Val Asp Val

265

Ser His Glu Asp Pro

270

Val Lys Phe Asn Trp

275

Tyr Val Asp Gly Val

280

Glu Val His Asn Ala

285

Thr Lys Pro Arg Glu

290

Glu Gln Tyr Asn Ser

295

Thr Tyr Arg Val Val

300

Val Leu Thr Val Leu 305

His Gln Asp Trp Leu 310

Asn Gly Lys Glu Tyr 315

Cys Lys Val Ser Asn

325

Lys Ala Leu Pro Ala

330

Pro Ile Glu Lys Thr

335

Ser Lys Ala Lys Gly

340

Gln Pro Arg Glu Pro

345

Gln Val Tyr Thr Leu

350

Pro Ser Arg Asp Glu

355

Leu Thr Lys Asn Gln 360

Val Ser Leu Thr Cys 365

Val Lys Gly Phe Tyr

370

Pro Ser Asp Ile Ala

375

Val Glu Trp Glu Ser

380

Gly Gln Pro Glu Asn 385

Asn Tyr Lys Thr Thr 390

Pro Pro Val Leu Asp 395

Asp Gly Ser Phe Phe

Leu Tyr Ser Lys Leu

Thr Val Asp Lys Ser

Ser

Ser

Asn

His

Val 240

Thr

Glu

Lys

Ser

Lys 320

Ile

Pro

Leu

Asn

Ser 400

Arg

- 197 044746

405 410 415

Trp Gln Gln Gly Asn Val Phe Ser Cys

420 425

Ser Val Met His Glu Ala Leu

430

His Asn His Tyr Thr Gln Lys Ser Leu

435 440

Ser Leu Ser Pro Gly Lys

445 <210> 96 <211> 648 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 96 gacatccaga atcacttgtc gggaaagccc aggttcagcg gaagattttg cctgggacca ccatctgatg tatcccagag caggagagtg acgctgagca ggcctgagct tgacccagtc gggcgagtca ctaagctcct gcagtggatc caacttacta aagtgg atat agcagttgaa aggccaaagt tcacagagca aagcagacta cgcccgtcac tccatcttcc gggtattagc gatctatgct tgggacagat ttgtcaacag caaacgaact atctggaact acagtggaag ggacagcaag cgagaaacac aaagagcttc gtgtctgcat agctggttag gcatccagtt tt cactctca gctaacagtt gtggctgcac gcctctgttg gtggataacg gacagcacct aaagtctacg aacaggggag ctgtaggaga cctggtatca tgcaaagtgg ccatcagcag tccccctatt catctgtctt tgtgcctgct ccctccaatc acagcctcag cctgcgaagt agtgttag cagagtcacc gcagaaacca ggtcccatca cctgcagcct cactttcggc catcttcccg ga ataacttc gggtaactcc cagcaccctg cacccatcag

120

180

240

300

360

420

480

540

600

648 <210> 97 <211> 215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 97

Asp Ile 1

Gln Met

Thr Gln 5

Ser Pro

Ser Ser

Val Ser

Ala Ser

Asp Arg

Val Thr

Ile Thr

CysArg

Ala Ser 25

Gln Gly

Ile Ser

Leu Ala

Trp Tyr 35

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

Lys Leu 45

Val Gly 15

Ser Trp

Leu Ile

- 198 044746

Tyr Ala 50

Ser Gly 65

Glu Asp

Phe Thr

Ala Pro

Ala Ser

Ser Gly

Phe Ala

Phe Gly

100

Ser Val 115

Ser Leu

Thr Asp 70

Thr Tyr 85

Pro Gly

Phe Ile

Gly Thr

130

Ala Ser

Val Val

Ala Lys 145

Val Gln

Trp Lys

150

Gln Glu

Ser Val

Thr Glu 165

Ser Ser

Thr Leu

180

Thr Leu

Tyr Ala

Cys Glu 195

Val Thr

Ser Phe Asn Arg Gly Glu

210

Gln Ser 55

Phe Thr

Tyr Cys

Thr Lys

Phe Pro

120

Cys Leu 135

Val Asp

Gln Asp

Ser Lys

His Gln

200

Cys 215

Gly Val

Leu Thr

Gln Gln

Val Asp 105

Pro Ser

Leu Asn

Asn Ala

Ser Lys

170

Ala Asp 185

Gly Leu <210> 98 <211> 357 <212> DNA <213> Artificial sequence

Synthetic <220>

<223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg gcagactctg tggtggagtc cctctggatt ggctggagtg tgaagggccg tgggggaggc caccttcagt ggtttcatac attcaccatc

Pro Ser

Ile Ser 75

Ala Asn

Ile Lys

Asp Glu

Asn Phe

140

Leu Gln 155

Asp Ser

Tyr Glu

Ser Ser ttggtacagc atttatgaaa attactagta tccagagaca

Arg Phe

Ser Leu

Ser Phe

Arg Thr

110

Gln Leu 125

Tyr Pro

Ser Gly

Thr Tyr

Lys His

190

Pro Val 205 ctggagggtc tgaactgggt gtggtactac acgccaagaa

Ser Gly

Glin Pro

Pro Leu 95

Val Ala

Lys Ser

Arg Glu

Asn Ser

160

Ser Leu 175

Lys Val

Thr Lys cctgagactc ccgccaggct catatactac ctcactgtat

120

180

240

- 199 044746 ctgcaaatga tcgtccgggt acagcctgag actactttga agccgaggac ctactggggc acggctgttt cagggaaccc attactgtgc tggtcaccgt gagtagcagc ctcctca

300

357 <210> 99 <211> 119 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 99

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Ser Ile Tyr

thirty

Glu Met Asn Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Tyr Ile Thr Ser Ser Gly Thr

55

Thr Ile Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ala Lys Asn Ser Leu Tyr

80

Leu Gln Met Asn Ser Leu Arg Ala 85

Glu Asp Thr Ala Val Tyr Tyr Cys

95

Ala Ser Ser Ser Ser Ser Gly Tyr

100

Tyr Phe Asp Tyr Trp Gly Gln Gly

105 110

Thr Leu Val Thr Val Ser Ser

115 <210> 100 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>100 ggattcacct tcagtattta tgaa <210>101 <211>8 <212> PROTEIN <213> Artificial sequence

- 200 044746 <220>

<223> Synthetic <400>101

Gly Phe Thr Phe Ser Ile Tyr Glu 15 <210>102 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>102 attactagta gtggtactac cata24 <210>103 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>103

Ile Thr Ser Ser Gly Thr Thr Ile <210>104 <211>36 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>104 gcgagtagca gctcgtccgg gtactacttt gactac36 <210>105 <211>12 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 105

Ala Ser Ser Ser Ser Gly Tyr Tyr Phe Asp Tyr

5 10 <210> 106

- 201 044746 <211> 339 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>106 gacatcgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc60 atcaactgca agtccagcca gagtgtttta tacagctcca acaataagaa ctacttagct120 tggtaccagc agaaaccagg acagcctcct aatctgctca tttact gggc atctacccgg180 gaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc240 atcagcagcc tgcaggctga agatgtggca gtttattact gtcagcaata ttatagtact300 cctcccactt ttggccaggg gaccaagctg gagatcaaa339 <210> 107 <211>113 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>107

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

5 1015

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser 20 2530

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 35 4045

Pro Pro Asn Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val 50 5560

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 65 70 7580

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln 85 9095

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

100 105110

Lys

- 202 044746 <210> 108 <211> 36 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>108 cagagtgttt tatacagctc caacaataag aactac36 <210>109 <211>12 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>109

Gln Ser Val Leu Tyr Ser Ser Asn Asn Lys Asn Tyr

510 < 210> 110 < 211> 9 < 212> DNA < 213> Artificial sequence <220>

< 223> Synthetic < 400>110 tgggcatct < 210>111 < 211>3 < 212> PROTEIN < 213> Artificial sequence <220>

< 223> Synthetic < 400>111

Trp Ala Ser < 210 > 112 < 211 > 27 < 212 > DNA < 213 > Artificial sequence < 220 >

< 223> Synthetic < 400> 112 cagcaatatt atagtactcc tcccact

- 203 044746 <210> 113 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>113

Gln Gln Tyr Tyr Ser Thr Pro Pro Thr <210>114 <211>1350 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 114 gaggtgcagc tggtggagtc tgggggaggc ttggtacagc ctggagggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagt atttatgaaa tgaactgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtttcatac attactagta gtggtactac catatactac 180 gcagactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240 ctgcaaatga acagcctgag agccgaggac acggctgttt attackgtgc gagtagcagc 300 tcgtccggggt actactttga ctactggggc cagggaaccc tggtcaccgt ctcctcagcc 360 tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctggggggc 420 acaggccc tggggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac ccagacctac 600 atctgcaacg tgaatcacaa gccagcaac accaaggtgg acaagaaagt tgagcccaaa 660 tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720 tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780 gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840 gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900 acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaagggag 960 tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020 gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080 accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140 gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200

- 204 044746 aagctcaccg catgaggctc tggacaagag tgcacaacca caggtggcag ctacacgcag gactccgacg caggggaacg aagtccctct gctccttctt tcttctcatg ccctgtctcc cctctacagc ctccgtgatg gggtaaatga

1260

1320

1350 <210> 115 <211> 449 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 115

Glu Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly 10

Leu Val

Glin Pro

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Phe Thr

Phe Ser

GluMet

Asn Trp 35

Val Arg

Gln Ala

Pro Gly

Lys Gly

Leu Glu 45

Ser Tyr 50

Ile Thr

Ser Ser

Gly Thr 55

Thr Ile

Tyr Tyr 60

Ala Asp

Gly Gly 15

Ile Tyr

Trp Val

Ser Val

Lys Gly 65

Arg Phe

Thr Ile

Ser Arg

Asp Asn

Ala Lys 75

Asn Ser

Leu Tyr 80

Leu Gln

Met Asn

Ser Leu 85

Arg Ala

Glu Asp 90

Thr Ala

Val Tyr

Tyr Cys 95

Ala Ser

Ser Ser

100

Ser Ser

Gly Tyr

Tyr Phe 105

Asp Tyr

Trp Gly

110

Gln Gly

Thr Leu

Val Thr

115

Val Ser

Ser Ala

120

Ser Thr

Lys Gly

Pro Ser 125

Val Phe

ProLeu

130

Ala Pro

Ser Ser

Lys Ser 135

Gly Cys 145

Leu Val

Lys Asp

150

Tyr Phe

Asn Ser

Gly Ala

Leu Thr 165

Ser Gly

Gln Ser

Ser Gly

Leu Tyr

Ser Leu

Thr Ser

Pro Glu

Val His

170

Ser Ser

Gly Gly

140

Thr Ala

Ala Leu

Pro Val 155

Thr Val

Ser Trp

160

Thr Phe

Pro Ala

Val Leu

175

Val Val

Thr Val

Pro Ser

- 205 044746

180

185

190

Ser Ser Leu Gly Thr

195

Gln Thr Tyr Ile Cys 200

Asn Val Asn His Lys 205

Ser Asn Thr Lys Val

210

Asp Lys Lys Val Glu

215

Pro Lys Ser Cys Asp 220

Thr His Thr Cys Pro 225

Pro Cys Pro Ala Pro 230

Glu Leu Leu Gly Gly 235

Ser Val Phe Leu Phe

245

Pro Pro Lys Pro Lys

250

Asp Thr Leu Met Ile

255

Arg Thr Pro Glu Val

260

Thr Cys Val Val Val

265

Asp Val Ser His Glu

270

Pro Glu Val Lys Phe

275

Asn Trp Tyr Val Asp

280

Gly Val Glu Val His

285

Ala Lys Thr Lys Pro 290

Arg Glu Glu Gln Tyr

295

Asn Ser Thr Tyr Arg 300

Val Ser Val Leu Thr 305

Val Leu His Gln Asp 310

Trp Leu Asn Gly Lys 315

Tyr Lys Cys Lys Val

325

Ser Asn Lys Ala Leu

330

Pro Ala Pro Ile Glu

335

Thr Ile Ser Lys Ala

340

Lys Gly Gln Pro Arg

345

Glu Pro Gln Val Tyr

350

Leu Pro Pro Ser Arg

355

Asp Glu Leu Thr Lys 360

Asn Gln Val Ser Leu

365

Cys Leu Val Lys Gly

370

Phe Tyr Pro Ser Asp

375

Ile Ala Val Glu Trp

380

Ser Asn Gly Gln Pro 385

Glu Asn Asn Tyr Lys 390

Thr Thr Pro Pro Val 395

Asp Ser Asp Gly Ser

405

Phe Phe Leu Tyr Ser

410

Lys Leu Thr Val Asp

415

Ser Arg Trp Gln Gln

420

Gly Asn Val Phe Ser

425

Cys Ser Val Met His

430

Pro

Lys

Pro 240

Ser

Asp

Asn

Val

Glu 320

Lys

Thr

Thr

Glu

Leu 400

Lys

Glu

- 206 044746

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

435 440445

Lys <210>116 <211>663 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>116 gacatcgtga tgacccagtc tccagactcc ctggctgtgt ctctgggcga gagggccacc60 atcaactgca agtccagcca gagtgtttta tacagctcca acaataagaa ctacttagct120 tggtaccagc agaaaccagg acagcctcct aatctgctca ttt actgggc atctacccgg180 gaatccgggg tccctgaccg attcagtggc agcgggtctg ggacagattt cactctcacc240 atcagcagcc tgcaggctga agatgtggca gtttattact gtcagcaata ttatagtact300 cctcccactt ttggccaggg gaccaagctg gagatcaaac gaactgtggc tgcaccatct360 gtcttcatct tcccgccatc tgatgagcag ttgaaatctg gaactgcctc tgttgtgtgc420 ctgctgaata acttctatcc cagagaggcc aaagtacagt ggaaggtgga taacgccctc480 caatcgggta actcccagga gagtgtcaca gagcaggaca gcaaggacag cacctacagc540 ctcagcagca ccctgacgct gagcaaagca gactacgaga aacacaaagt ctacgcctgc600 gaagtcaccc atcagggcct gagctcgccc gtcacaaaga gcttcaacag gggagagtgt660 tag663 <210>117 <211>220 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>117

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

5 1015

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser 20 2530

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln 35 4045

- 207 044746

Pro Pro

Asn Leu

Leu Ile

Pro Asp 65

Arg Phe

Ser Gly 70

Ile Ser

Ser Leu

Gln Ala 85

Tyr Tyr

Ser Thr

100

Pro Pro

Tyr Trp 55

Ser Gly

Glu Asp

Thr Phe

Ala Ser

Ser Gly

Val Ala

Gly Gln 105

Lys Arg

Thr Val 115

Ala Ala

Pro Ser

120

Val Phe

Glu Gln

130

Leu Lys

Ser Gly

Thr Ala 135

Ser Val

Thr Arg 60

Thr Asp 75

Val Tyr

Gly Thr

Ile Phe

Val Cys

140

Glu Ser

Phe Thr

Tyr Cys

Lys Leu

110

Pro Pro 125

Leu Leu

Gly Val

Leu Thr

Gln Gln 95

Glu Ile

Ser Asp

Asn Asn

Phe Tyr 145

Pro Arg

Glu Ala

150

Lys Val

Gln Trp

Lys Val 155

Asp Asn

Ala Leu

160

Gln Ser

Gly Asn

Ser Gln 165

Glu Ser

Val Thr

170

Glu Gln

Asp Ser

Lys Asp 175

Ser Thr

Tyr Ser

180

Leu Ser

Ser Thr

Leu Thr 185

Leu Ser

Lys Ala

190

Asp Tyr

Glu Lys

His Lys 195

Val Tyr

Ala Cys

200

Glu Val

Thr His

Gln Gly 205

Leu Ser

Ser Pro

210

Val Thr

Lys Ser

Phe Asn 215

Arg Gly

Glu Cys

220 <210> 118 <211> 363 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic <400> 118 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc tcctgcaagg cctggacaag cttctggata ggcttgagtg caccttcatt gatgggatgg aactactata atcaacccta gcacagaagt atggagctga ttcagggcag gcaggctgag ggtcacca tg atctgacgac accagggaca acggccgtgt ctggggcctc agtgaaggtc tacactgggt gcgacaggcc acagtggtgg cacaaactat cgtccatcag cacagcctac attactgtgc gattattacg

120

180

240

300

- 208 044746 atttttggag tggttacctg gttcgacccc tggggccagg gaaccctggt caccgtctcc

360

363 tca <210> 119 <211> 121 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 119

Gln Val Gln Leu Val Gln Ser Gly 1 5

Ala Glu Val Lys Lys Pro Gly Ala

15

Ser Val Lys Val Ser Cys Lys Ala 20

Ser Gly Tyr Thr Phe Ile Asn Tyr 25 30

Tyr Ile His Trp Val Arg Gln Ala

40

Pro Gly Gln Gly Leu Glu Trp Met 45

Gly Trp Ile Asn Pro Asn Ser Gly

55

Gly Thr Asn Tyr Ala Gln Lys Phe 60

Gln Gly Arg Val Thr Met Thr Arg 65 70

Asp Thr Ser Ile Ser Thr Ala Tyr

80

Met Glu Leu Ser Arg Leu Arg Ser 85

Asp Asp Thr Ala Val Tyr Tyr Cys

95

Ala Ile Ile Thr Ile Phe Gly Val

100

Val Thr Trp Phe Asp Pro Trp Gly

105 110

Gln Gly Thr Leu Val Thr Val Ser

115120

Ser <210>120 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 120 ggatacacct tcattaacta ctat <210> 121 <211> 8 <212> PROTEIN

- 209 044746 <213> Artificial sequence <220>

<223> Synthetic <400>121

Gly Tyr Thr Phe Ile Asn Tyr Tyr <210>122 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>122 atcaacccta acagtggtgg caca24 <210>123 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>123

Ile Asn Pro Asn Ser Gly Gly Thr <210>124 <211>42 <212> DNA <213> Artificial Sequence <220>

<223> Synthetic <400>124 gcgattatta cgatttttgg agtggttacc tggttcgacc cc42 <210>125 <211>14 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 125

Ala Ile Ile Thr Ile Phe Gly Val Val Thr Trp Phe Asp Pro

5 10

- 210 044746 <210> 126 <211> 321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 126

gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180 aggttcagtg gcagtggatc tggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagatttg caactacta ctgtcaacag agttacagta ccccgctcac tttcggcgga 300 gggaccaagg tggagatcaa a 321

<210> 127 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>127

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100105 <210> 128 <211> 18 <212> DNA

- 211 044746 <213> Artificial sequence <220>

<223> Synthetic <400> 128 cagagcatta gcagctat <210> 129 <211> 6 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 129

Gln Ser Ile Ser Ser Tyr 1 5 <210> 130 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 130 caacagagtt acagtacccc gctcact <210> 131 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 131

Gln Gln Ser Tyr Ser Thr Pro Leu Thr <210> 132 <211> 1356 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 132 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60 tcctgcaagg cttctggata caccttcatt aactactata tacactgggt gcgacaggcc

120 cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgg cacaaactat

180

- 212 044746

gcacagaagt ttcaggggcag ggtcaccatg accagggaca cgtccatcag cacagcctac 240 atggagctga gcaggctgag atctgacgac acggccgtgt attackgtgc gattattacg 300 atttttggag tggttacctg gttcgacccc tggggccagg gaaccctggt caccgtctcc 360 tcagcctcca ccaagggccc atcggtcttc cccctggcac cctcctccaa gagcacctct 420 gggggcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg 480 tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc 540 tcaggactct actccctcag cagcgtggtg accgtgccct ccagcagctt gggcacccag 600 acctacatct gcaacgtgaa tcacaagccc agcaacacca aggtggacaa gaaagttgag 660 cccaaatctt gtgacaaaac tcacacatgc ccaccgtgcc cagcacctga actcctgggg 720 ggaccgtcag tcttcctctt ccccccaaaa cccaaggaca ccctcatgat ctcccggacc 780 cctgaggtca catgcgtggt ggtggacgtg agccacgaag accctgaggt caagttcaac 840 tggtacgtgg acggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagtac 900 aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaatggc 960 aaggagtaca agtgcaaggt ctccaacaaa gccctcccag ccccatcga gaaaaccatc 1020 tccaaagcca aagggcagcc ccgagaacca caggtgtaca ccctgccccc atcccgggat 1080 gagctgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta tccagcgac 1140 atcgccgtgg agggggagag caatggggcag ccggagaaca actacaagac cacgcctccc 1200 gtgctggact ccgacggctc cttcttcctc tacagcaagc tcaccgtgga caagagcagg 1260 tggcagcagg ggaacgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac 1320 acgcagaagt ccctctccct gtctccggggt aaatga 1356

<210> 133 <211> 451 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>133

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

5 1015

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ile Asn Tyr 20 2530

Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 4045

- 213 044746

Gly

Gln 65

Met

Ala

Gln

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Gly

Ile

Glu

His

Trp Ile Asn Pro Asn 50

Gly Arg Val Thr Met 70

Glu Leu Ser Arg Leu 85

Ile Ile Thr Ile Phe

100

Gly Thr Leu Val Thr 115

Phe Pro Leu Ala Pro 130

Leu Gly Cys Leu Val

150

Trp Asn Ser Gly Ala

165

Leu Gln Ser Ser Gly 180

Ser Ser Ser Leu Gly 195

Pro Ser Asn Thr Lys 210

Lys Thr His Thr Cys

230

Pro Ser Val Phe Leu

245

Ser Arg Thr Pro Glu

260

Asp Pro Glu Val Lys

275

Asn Ala Lys Thr Lys 290

Ser Gly Gly Thr Asn 55

Thr Arg Asp Thr Ser

Arg Ser Asp Asp Thr

Gly Val Val Thr Trp

105

Val Ser Ser Ala Ser

120

Ser Ser Lys Ser Thr 135

Lys Asp Tyr Phe Pro

155

Leu Thr Ser Gly Val

170

Leu Tyr Ser Leu Ser 185

Thr Gln Thr Tyr Ile 200

Val Asp Lys Lys Val 215

Pro Pro Cys Pro Ala

235

Phe Pro Pro Lys Pro

250

Val Thr Cys Val Val

265

Phe Asn Trp Tyr Val

280

Pro Arg Glu Glu Gln 295

Tyr Ala Gln Lys Phe 60

Ile Ser Thr Ala Tyr 80

Ala Val Tyr Tyr Cys 95

Phe Asp Pro Trp Gly

110

Thr Lys Gly Pro Ser

125

Ser Gly Gly Thr Ala 140

Glu Pro Val Thr Val

160

His Thr Phe Pro Ala

175

Ser Val Val Thr Val

190

Cys Asn Val Asn His

205

Glu Pro Lys Ser Cys 220

Pro Glu Leu Leu Gly

240

Lys Asp Thr Leu Met

255

Val Asp Val Ser His

270

Asp Gly Val Glu Val

285

Tyr Asn Ser Thr Tyr 300

- 214 044746

Arg Val 305

Lys Glu

Glu Lys

Tyr Thr

Leu Thr 370

Trp Glu 385

Val Leu

Asp Lys

His Glu

Val Ser

Tyr Lys

Thr Ile

340

Leu Pro 355

Cys Leu

Ser Asn

Asp Ser

Ser Arg

420

Ala Leu 435

Pro Gly Lys

450 <210>

<211>

<212>

<213>

<220>

Val Leu

310

Cys Lys 325

Ser Lys

Pro Ser

Val Lys

Gly Gln

390

Asp Gly 405

Trp Gln

His Asn

Thr Val

Val Ser

Ala Lys

Arg Asp

360

Gly Phe 375

Pro Glu

Ser Phe

Gln Gly

His Tyr

440

Leu His

Asn Lys

330

Gly Gln 345

Glu Leu

Tyr Pro

Asn Asn

Phe Leu

410

Asn Val 425

Thr Gln

134

645

DNA

Artificial sequence <223> Synthetic <400> 134 gacatccaga atcacttgcc gggaaagccc aggttcagtg gaagattttg gggaccaagg tgacccagtc gggcaagtca ctaagctcct gcagtggatc caacttacta tggagatcaa tccatcctcc gagcattagc gatctatgct tgggacagat ctgtcaacag acgaactgtg

Gln Asp 315

Ala Leu

Pro Arg

Thr Lys

Ser Asp 380

Tyr Lys 395

Tyr Ser

Phe Ser

Lys Ser ctgtctgcat agctatttaa gcatccagtt ttcactctca agttacagta gctgcaccat

Trp Leu

Pro Ala

Glu Pro

350

Asn Gln 365

Ile Ala

Thr Thr

Lys Leu

Cys Ser

430

Leu Ser 445 ctgtaggaga attggtatca tgcaaagtgg ccatcagcag ccccgctcac ctgtcttcat

Asn Gly

320

Pro Ile 335

Gln Val

Val Ser

Val Glu

Pro Pro

400

Thr Val 415

Val Met

Leu Ser cagagtcacc gcagaaacca ggtcccatca tctgcaacct tttcggcgga cttcccgcca

120

180

240

300

360

- 215 044746 tctgatgagc cccagagagg gagagtgtca ctgagcaaag ctgagctcgc agttgaaatc ccaaagtaca cagagcagga cagactacga ccgtcacaaa tggaactgcc gtggaaggtg cagcaaggac gaaacacaaa gagcttcaac tctgttgtgt gataacgccc agcacctaca gtctacgcct aggggagagt gcctgctgaa tccaatcggg gcctcagcag gcgaagtcac gttag taacttctat taactcccag caccctgacg ccatcagggc

420

480

540

600

645 <210> 135 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 135

Asp Ile 1

Gln Met

Thr Gln 5

Ser Pro

Ser Ser

Leu Ser

Ala Ser

Asp Arg

Val Thr

Ile Thr

CysArg

Ala Ser 25

Gln Ser

Ile Ser

Leu Asn

Trp Tyr 35

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

Lys Leu 45

Tyr Ala 50

Ala Ser

Ser Leu

Gln Ser 55

Gly Val

Pro Ser

Arg Phe

Val Gly 15

Ser Tyr

Leu Ile

Ser Gly

Ser Gly 65

Ser Gly

Thr Asp 70

Phe Thr

Leu Thr

Ile Ser 75

Ser Leu

Glin Pro

Glu Asp

Phe Ala

Thr Tyr 85

Tyr Cys

Gln Gln

Ser Tyr

Ser Thr

Pro Leu 95

Thr Phe

Gly Gly

100

Gly Thr

Lys Val

Glu Ile 105

Lys Arg

Thr Val

110

Ala Ala

Pro Ser

Val Phe 115

Ile Phe

Pro Pro

120

Ser Asp

Glu Gln

Leu Lys 125

Ser Gly

Thr Ala

130

Ser Val

Val Cys

Leu Leu 135

Asn Asn

Phe Tyr

140

Pro Arg

Glu Ala

Lys Val 145

Gln Trp

Lys Val

150

Asp Asn

Ala Leu

Gln Ser 155

Gly Asn

Ser Gln

160

Glu Ser

Val Thr

Glu Gln 165

Asp Ser

Lys Asp

170

Ser Thr

Tyr Ser

Leu Ser 175

- 216 044746

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

180 185

Lys His Lys Val Tyr 190

Ala Cys

Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200 205

Phe Asn Arg Gly Glu Cys

210

136

345

DNA

Artificial

Synthetic

136 <210>

<211>

<212>

<213>

<220>

<223>

<400>

caggtgcagc acctgcactg ccagggaagg ccctccctca aaactgagct ctcattgact sequence tgcaggagtc tctctggtgg gactggagtg agagtcgagt ctgtgaccgc actggggcca gggcccagga ctccatcagt gattgggtat caccatatca tgcggacacg gggaaccctg ctggtgaag c agttactact atctattaca gtagacacgt gccgtgtatt gtcaccgtct cttcggagac ggagttggat gtgggagcac ccaagaacca actgtgcgag cctca cctgtccctc ccggcagccc caactacaac gttctccctg agacccgctc

120

180

240

300

345 <210> 137 <211> 115 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>137

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

5 1015

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Tyr 20 2530

Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile 35 4045

Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys 50 5560

Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu

- 217 044746

Lys Leu

Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala

90 95

Arg Asp Pro Leu Leu Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr

100 105 110

Val Ser Ser

115 <210> 138 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 138 ggtggctcca tcagtagtta ctac <210> 139 <211> 8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 139

Gly Gly Ser Ile Ser Ser Tyr Tyr

5 <210> 140 <211> 21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 140 atctattaca gtgggagcac c <210> 141 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 141

- 218 044746

Ile Tyr Tyr Ser Gly Ser Thr <210> 142 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>142 gcgagagacc cgctcctcat tgactac <210>143 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>143

Ala Arg Asp Pro Leu Leu Ile Asp Tyr <210>144 <211>324 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 144

gaaattgtgt tgacgcagtc tccaggtacc ctgtctttgt ctccagggga aagagccacc 60 ctctcctgca gggccagtca gagtgttagt agaagctact tagcctggta ccagcagaaa 120 cctggccagg ctcccaggct cctcatcatat ggtgtatcca gcaggggccac tggcatccca 180 gacaggttca gcggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240 cctgaagatt ttgcagtgta ttattgtcag cagtatggta gctcacctca gacttttggc 300 caggggacca agctggagat caaa 324

<210> 145 <211> 108 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 145

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

- 219 044746

Glu Arg Ala Thr Leu Ser Cys Arg 20

Ala Ser Gln Ser Val Ser Arg Ser 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys

40

Pro Gly Gln Ala Pro Arg Leu Leu 45

Ile Tyr Gly Val Ser Ser Arg Ala

55

Thr Gly Ile Pro Asp Arg Phe Ser 60

Gly Ser Gly Ser Gly Thr Asp Phe 65 70

Thr Leu Thr Ile Ser Arg Leu Glu

80

Pro Glu Asp Phe Ala Val Tyr Tyr 85

Cys Gln Gln Tyr Gly Ser Ser Pro

95

Gln Thr Phe Gly Gln Gly Thr Lys

100

Leu Glu Ile Lys 105 <210> 146 <211> 21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>146 cagagtgtta gtagaagcta c <210>147 <211>7 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>147

Gln Ser Val Ser Arg Ser Tyr <210>148 <211>9 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 148 ggtgtatcc

- 220 044746 <210> 149 <211> 3 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>149

Gly Val Ser < 210 > 150 < 211 > 27 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic <400>150 cagcagtatg gtagctcacc tcagact <210>151 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>151

Gln Gln Tyr Gly Ser Ser Pro Gln Thr <210>152 <211>1338 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>152 caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcggagac cctgtccctc60 acctgcactg tctctggtgg ctccatcagt agttactact ggagttggat ccggcagccc120 ccagggaagg gactggagtg gattgggtat atctattaca gtgggagcac caactacaac180 ccctccctca agagtcgagt caccatatca gtagacacgt ccaagaacca gttctccctg240 aaactgagct ctgtgaccgc tgcggacacg gccgtgtatt actgtgcgag agacccgctc300 ctcattgact actggggcca gggaaccctg gt caccgtct cctcagcctc caccaagggc360

- 221 044746

ccatcggtct tccccctggc accctcctcc aagagcacct ctggggggcac agcggccctg 420 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540 agcagcgtgg tgaccgtgcc ctccagcagc ttggggcaccc agacctacat ctgcaacgtg 600 aatcacaagc ccagcaacac caaggtggac aagaaagttg agcccaaatc ttgtgacaaa 660 actcacacat gccaccgtg cccagcacct gaactcctgg ggggaccgtc agtcttcctc 720 ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 780 gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 840 gaggtgcata atgccaagac aaagccgcgg gagggagt acaacagcac gtaccgtgtg 900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaatg gcaagggagta caagtgcaag 960 gtctccaaca aagccctccc agcccccatc gagaaaacca tctccaaagc caaagggcag 1020 ccccgagaac cacaggtgta caccctgccc ccaccccgggg atgagctgac caagaaccag 1080 gtcagcctga cctgcctggt caaaggcttc tatcccagcg acatcgccgt ggagtggggag 1140 agcaatggggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200 tccttcttcc tctacagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gtccctctcc 1320 ctgtctccgg gtaaatga 1338

<210> 153 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>153

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

5 1015

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Tyr 20 2530

Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile 35 4045

Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys 50 5560

Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu 65 70 7580

- 222 044746

Lys Leu Ser Ser Val 85

Thr Ala Ala Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Asp Pro Leu Leu

100

Ile Asp Tyr Trp Gly

105

Gln Gly Thr Leu Val

110

Val Ser Ser Ala Ser

115

Thr Lys Gly Pro Ser

120

Val Phe Pro Leu Ala

125

Ser Ser Lys Ser Thr 130

Ser Gly Gly Thr Ala

135

Ala Leu Gly Cys Leu

140

Lys Asp Tyr Phe Pro 145

Glu Pro Val Thr Val 150

Ser Trp Asn Ser Gly 155

Leu Thr Ser Gly Val

165

His Thr Phe Pro Ala

170

Val Leu Gln Ser Ser

175

Leu Tyr Ser Leu Ser

180

Ser Val Val Thr Val

185

Pro Ser Ser Ser Leu

190

Thr Gln Thr Tyr Ile 195

Cys Asn Val Asn His

200

Lys Pro Ser Asn Thr

205

Val Asp Lys Lys Val

210

Glu Pro Lys Ser Cys

215

Asp Lys Thr His Thr 220

Pro Pro Cys Pro Ala 225

Pro Glu Leu Leu Gly 230

Gly Pro Ser Val Phe 235

Phe Pro Pro Lys Pro

245

Lys Asp Thr Leu Met

250

Ile Ser Arg Thr Pro

255

Val Thr Cys Val Val

260

Val Asp Val Ser His

265

Glu Asp Pro Glu Val

270

Phe Asn Trp Tyr Val

275

Asp Gly Val Glu Val 280

His Asn Ala Lys Thr

285

Pro Arg Glu Glu Gln

290

Tyr Asn Ser Thr Tyr

295

Arg Val Val Ser Val

300

Thr Val Leu His Gln 305

Asp Trp Leu Asn Gly 310

Lys Glu Tyr Lys Cys 315

Ala

Thr

Pro

Val

Ala 160

Gly

Gly

Lys

Cys

Leu 240

Glu

Lys

Lys

Leu

Lys 320

Lys

Val Ser Asn Lys Ala

Leu Pro Ala Pro Ile

Glu Lys Thr Ile Ser

- 223 044746

335

325

330

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345350

Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

355 360365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

370 375380

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

385 390 395400

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln

405 410415

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440445 <210>154 <211>648 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 154 gaaattgtgt ctctcctgca cctggccagg gacaggttca cctgaagatt caggggacca ccatctgatg tatcccagag caggagagtg acgctgagca ggcctgagct tgacgcagtc gggccagtca ctcccaggct gcggcagtgg ttgcagtgta ag ctggagat agcagttgaa aggccaaagt tcacagagca aagcagacta cgcccgtcac tccaggtacc gagtgttagt cctcatctat gtctgggaca ttattgtcag caaacgaact atctggaact acagtggaag ggacagcaag cgagaaacac aaagagcttc ctgtctttgt agaagctact ggtgtat cca gacttcactc cagtatggta gtggctgcac gcctctgttg gtggataacg gacagcacct aaagtctacg aacaggggag ctccagggga tagcctggta gcagggccac tcaccatcag gctcacctca catctgtctt tgtgcctgct ccctccaatc acagcctcag cctgcgaagt agtgttag aagagccacc ccagcagaaa tggcatccca cagactggag gacttttggc catcttcccg gaataacttc gggtaactcc cagcaccctg cacccatcag

120

180

240

300

360

420

480

540

600

648

- 224 044746 <210> 155 <211> 215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 155

Glu Ile Val Leu Thr

5

Gln Ser Pro Gly Thr

Leu Ser Leu Ser Pro

Glu Arg Ala Thr Leu

Ser Cys Arg Ala Ser

Gln Ser Val Ser Arg

Tyr Leu Ala Trp Tyr 35

Gln Gln Lys Pro Gly 40

Gln Ala Pro Arg Leu 45

Ile Tyr Gly Val Ser 50

Ser Arg Ala Thr Gly 55

Ile Pro Asp Arg Phe 60

Gly Ser Gly Ser Gly 65

Thr Asp Phe Thr Leu 70

Thr Ile Ser Arg Leu 75

Pro Glu Asp Phe Ala 85

Val Tyr Tyr Cys Gln 90

Gln Tyr Gly Ser Ser 95

Gln Thr Phe Gly Gln

100

Gly Thr Lys Leu Glu

105

Ile Lys Arg Thr Val

110

Ala Pro Ser Val Phe

115

Ile Phe Pro Pro Ser

120

Asp Glu Gln Leu Lys 125

Gly Thr Ala Ser Val 130

Val Cys Leu Leu Asn

135

Asn Phe Tyr Pro Arg 140

Ala Lys Val Gln Trp 145

Lys Val Asp Asn Ala 150

Leu Gln Ser Gly Asn 155

Gln Glu Ser Val Thr

165

Glu Gln Asp Ser Lys

170

Asp Ser Thr Tyr Ser

175

Ser Ser Thr Leu Thr

180

Leu Ser Lys Ala Asp

185

Tyr Glu Lys His Lys

190

Tyr Ala Cys Glu Val 195

Thr His Gln Gly Leu 200

Ser Ser Pro Val Thr

205

Gly

Ser

Leu

Ser

Glu 80

Pro

Ala

Ser

Glu

Ser 160

Leu

Val

Lys

Ser Phe Asn Arg Gly

Glu Cys

- 225 044746

210

215 <210> 156 <211> 1341 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 156

caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgtgcag cgtctggatt caccttcagt tactatggca tgcactgggt ccgccaggct 120 ccaggcaagg ggctggagtg ggtggcagtt atatggtatg atggaagtaa taaattctat 180 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaggac acggctgtgt attackgtgc ggcagctcgg 300 ccggggctact actacggtat ggacgtctgg ggccaaggga ccacggtcac cgtctcctca 360 gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 420 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacgaagacc 600 tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 660 aaatatggtc ccccatgccc accgtgccca gcaccaggcg gtggcggacc atcagtcttc 720 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 780 gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 840 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cagtaccgt 900 gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 960 aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1020 cagccccgag agccacaggt gtacaccctg ccccatccc aggaggat gaccaagaac 1080 caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1140 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1200 ggctccttct tcctctacag caggctcacc gtggacaaga gcaggtggca ggaggggaat 1260 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagtccctc 1320 tccctgtctc tgggtaaatg a 1341

<210> 157 <211> 446 <212> PROTEIN <213> Artificial sequence

- 226 044746 <220>

<223> Synthetic <400> 157

Gln Val Gln Leu Val 1 5

Glu Ser Gly Gly Gly 10

Val Val Gln Pro Gly

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Phe Thr Phe Ser Tyr 30

Gly Met His Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Ala Val Ile Trp Tyr 50

Asp Gly Ser Asn Lys 55

Phe Tyr Ala Asp Ser 60

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Asn 70

Ser Lys Asn Thr Leu 75

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Ala Ala Arg Pro

100

Gly Tyr Tyr Tyr Gly

105

Met Asp Val Trp Gly

110

Gly Thr Thr Val Thr 115

Val Ser Ser Ala Ser

120

Thr Lys Gly Pro Ser

125

Phe Pro Leu Ala Pro

130

Cys Ser Arg Ser Thr

135

Ser Glu Ser Thr Ala

140

Leu Gly Cys Leu Val 145

Lys Asp Tyr Phe Pro 150

Glu Pro Val Thr Val 155

Trp Asn Ser Gly Ala

165

Leu Thr Ser Gly Val

170

His Thr Phe Pro Ala

175

Leu Gln Ser Ser Gly

180

Leu Tyr Ser Leu Ser

185

Ser Val Val Thr Val

190

Ser Ser Ser Leu Gly 195

Thr Lys Thr Tyr Thr 200

Cys Asn Val Asp His

205

Pro Ser Asn Thr Lys 210

Val Asp Lys Arg Val

215

Glu Ser Lys Tyr Gly 220

Pro Cys Pro Pro Cys

Pro Ala Pro Gly Gly

Gly Gly Pro Ser Val

Arg

Tyr

Val

Val

Tyr 80

Cys

Gln

Val

Ala

Ser 160

Val

Pro

Lys

Pro

Phe

- 227 044746

225

230

235

Leu Phe Pro Pro Lys

245

Pro Lys Asp Thr Leu

250

Met Ile Ser Arg Thr

255

Glu Val Thr Cys Val

260

Val Val Asp Val Ser

265

Gln Glu Asp Pro Glu

270

Gln Phe Asn Trp Tyr

275

Val Asp Gly Val Glu

280

Val His Asn Ala Lys

285

Lys Pro Arg Glu Glu

290

Gln Phe Asn Ser Thr

295

Tyr Arg Val Val Ser

300

Leu Thr Val Leu His 305

Gln Asp Trp Leu Asn 310

Gly Lys Glu Tyr Lys 315

Lys Val Ser Asn Lys

325

Gly Leu Pro Ser Ser

330

Ile Glu Lys Thr Ile

335

Lys Ala Lys Gly Gln

340

Pro Arg Glu Pro Gln

345

Val Tyr Thr Leu Pro

350

Ser Gln Glu Glu Met

355

Thr Lys Asn Gln Val

360

Ser Leu Thr Cys Leu

365

Lys Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val

375

Glu Trp Glu Ser Asn

380

Gln Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro 390

Pro Val Leu Asp Ser 395

Gly Ser Phe Phe Leu

405

Tyr Ser Arg Leu Thr

410

Val Asp Lys Ser Arg

415

Gln Glu Gly Asn Val

420

Phe Ser Cys Ser Val

425

Met His Glu Ala Leu

430

240

Pro

Val

Thr

Val

Cys 320

Ser

Pro

Val

Gly

Asp 400

Trp

His

Asn His Tyr Thr Gln 435

Lys Ser Leu Ser Leu 440

Ser Leu Gly Lys

445 <210> 158 <211> 1332 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic

- 228 044746 <400> 158

gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctgggat caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agaacgtaac 300 tttgatgctt ttgatatctg gggccaaggg acaatggtca ccgtctcttc agcctccacc 360 aagggcccat cggtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc 420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctacacctgc 600 aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt 660 ccccatgcc caccgtgccc agcaccaggc ggtggcggac catcagtctt cctgttcccc 720 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg 780 gacgtgagcc aggaagacc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 840 cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 900 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 960 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1020 gagccacagg tgtacaccct gcccccatcc caggagaga tgaccaagaa ccaggtcagc 1080 ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1140 gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1200 ttcctctaca gcaggctcac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1260 tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagtccct ctccctgtct 1320

ctgggtaaat ga

1332 < 210> 159 < 211> 443 < 212> PROTEIN < 213> Artificial sequence < 220>

< 223> Synthetic <400> 159

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

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

- 229 044746

Tyr Met Ser Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Ser Val Ile Tyr Ser 50

Gly Gly Ser Thr Phe 55

Tyr Ala Asp Ser Val 60

Gly Arg Phe Thr Ile 65

Ser Arg His Asn Ser 70

Lys Asn Thr Leu Tyr 75

Gln Met Asn Ser Leu

Arg Ala Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Glu Arg Asn Phe

100

Asp Ala Phe Asp Ile

105

Trp Gly Gln Gly Thr

110

Val Thr Val Ser Ser

115

Ala Ser Thr Lys Gly 120

Pro Ser Val Phe Pro

125

Ala Pro Cys Ser Arg 130

Ser Thr Ser Glu Ser

135

Thr Ala Ala Leu Gly 140

Leu Val Lys Asp Tyr 145

Phe Pro Glu Pro Val 150

Thr Val Ser Trp Asn 155

Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe

170

Pro Ala Val Leu Gln

175

Ser Gly Leu Tyr Ser

180

Leu Ser Ser Val Val

185

Thr Val Pro Ser Ser

190

Leu Gly Thr Lys Thr 195

Tyr Thr Cys Asn Val 200

Asp His Lys Pro Ser 205

Thr Lys Val Asp Lys

210

Arg Val Glu Ser Lys

215

Tyr Gly Pro Pro Cys

220

Pro Cys Pro Ala Pro 225

Gly Gly Gly Gly Pro 230

Ser Val Phe Leu Phe 235

Pro Lys Pro Lys Asp

245

Thr Leu Met Ile Ser

250

Arg Thr Pro Glu Val

255

Cys Val Val Val Asp

260

Val Ser Gln Glu Asp

265

Pro Glu Val Gln Phe

270

Val

Lys

Leu 80

Ala

Met

Leu

Cys

Ser 160

Ser

Ser

Asn

Pro

Pro 240

Thr

Asn

- 230 044746

Trp Tyr

Glu Glu

290

Leu His 305

Asn Lys

Val Asp 275

Gln Phe

Gln Asp

Gly Leu

Gly Val

Asn Ser

Trp Leu

310

Pro Ser 325

Gly Gln

Pro Arg

340

Glu Pro

GluMet

Thr Lys 355

Asn Gln

Glu Val

280

Thr Tyr 295

Asn Gly

Ser Ile

Gln Val

Val Ser

360

His Asn

Arg Val

Lys Glu

Glu Lys

330

Tyr Thr 345

Leu Thr

Ala Lys

Val Ser

300

Tyr Lys 315

Thr Ile

Leu Pro

Cys Leu

Tyr Pro

370

Ser Asp

Ile Ala

Val Glu 375

Trp Glu

Ser Asn

380

Asn Asn 385

Tyr Lys

Thr Thr

390

Pro Pro

Val Leu

Asp Ser 395

Phe Leu

Tyr Ser

Arg Leu 405

Thr Val

Asp Lys

410

Ser Arg

Asn Val

Phe Ser

420

Cys Ser

Val Met

His Glu 425

Ala Leu

Thr Gln

Lys Ser 435

Leu Ser

Leu Ser

440

Leu Gly

Lys <210> 160 <211> 1338 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic <400> 160 gaggtgcagc tggtggagtc tgggggaggc ttggtacagc tcctgtgcag ccagggaagg gcagactctg cctctggatt ggctggagtg tgaagggccg caccttcagt ggtttcatac attcaccatc atttatgaaa attactagta tccagagaca ctgcaaatga acagcctgag agccgaggac acggctgttt

Thr Lys 285

Val Leu

Cys Lys

Ser Lys

Pro Ser

350

Val Lys 365

Gly Gln

Asp Gly

Trp Gln

His Asn

430

Pro Arg

Thr Val

Val Ser

320

Ala Lys 335

Gln Glu

Gly Phe

Pro Glu

Ser Phe

400

Glu Gly 415

His Tyr ctggagggtc cctgagactc tgaactgggt ccgccaggct gtggtactac catatactac acgccaagaa ctcactgtat attactgtgc gagtagcagc

120

180

240

300

- 231 044746

tcgtccggggt actactttga ctactggggc cagggaaccc tggtcaccgt ctcctcagcc 360 tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc 420 acagccgccc tggggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac gaagacctac 600 acctgcaacg tagatcacaa gccagcaac accaaggtgg acaagagt tgagtccaaa 660 tatggtcccc catgcccacc gtgccagca ccaggcggtg gcggaccatc agtcttcctg 720 ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 780 gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 840 gaggtgcata atgccaagac aaagccgcgg gagggagt tcaacagcac gtaccgtgtg 900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaagggagta caagtgcaag 960 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1020 ccccgagagc cacaggtgta caccctgccc ccaccagg aggagatgac caagaaccag 1080 gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtggggag 1140 agcaatggggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200 tccttcttcc tctacagcag gctcaccgtg gacaagagca ggtggcagga ggggaatgtc 1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gtccctctcc 1320 ctgtctctgg gtaaatga 1338

<210> 161 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>161

Glu Val Gln Leu Val Glu Ser Gly 15

Gly Gly Leu Val Gln Pro Gly Gly

1015

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Ser Ile Tyr 25 30

Glu Met Asn Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Tyr Ile Thr Ser Ser Gly Thr

55

Thr Ile Tyr Tyr Ala Asp Ser Val 60

- 232 044746

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Asn 70

Ala Lys Asn Ser Leu 75

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Ser Ser Ser Ser

100

Ser Gly Tyr Tyr Phe

105

Asp Tyr Trp Gly Gln

110

Thr Leu Val Thr Val

115

Ser Ser Ala Ser Thr

120

Lys Gly Pro Ser Val 125

Pro Leu Ala Pro Cys 130

Ser Arg Ser Thr Ser

135

Glu Ser Thr Ala Ala

140

Gly Cys Leu Val Lys 145

Asp Tyr Phe Pro Glu 150

Pro Val Thr Val Ser 155

Asn Ser Gly Ala Leu

165

Thr Ser Gly Val His

170

Thr Phe Pro Ala Val

175

Gln Ser Ser Gly Leu

180

Tyr Ser Leu Ser Ser

185

Val Val Thr Val Pro

190

Ser Ser Leu Gly Thr

195

Lys Thr Tyr Thr Cys 200

Asn Val Asp His Lys 205

Ser Asn Thr Lys Val

210

Asp Lys Arg Val Glu

215

Ser Lys Tyr Gly Pro

220

Cys Pro Pro Cys Pro 225

Ala Pro Gly Gly Gly 230

Gly Pro Ser Val Phe 235

Phe Pro Pro Lys Pro

245

Lys Asp Thr Leu Met

250

Ile Ser Arg Thr Pro

255

Val Thr Cys Val Val

260

Val Asp Val Ser Gln

265

Glu Asp Pro Glu Val

270

Phe Asn Trp Tyr Val

275

Asp Gly Val Glu Val 280

His Asn Ala Lys Thr

285

Pro Arg Glu Glu Gln 290

Phe Asn Ser Thr Tyr

295

Arg Val Val Ser Val

300

Thr Val Leu His Gln 305

Asp Trp Leu Asn Gly 310

Lys Glu Tyr Lys Cys 315

Tyr 80

Cys

Gly

Phe

Leu

Trp 160

Leu

Ser

Pro

Pro

Leu 240

Glu

Gln

Lys

Leu

Lys 320

- 233 044746

Val Ser

Asn Lys

Ala Lys

Gly Gln

340

Gln Glu

Glu Met 355

Gly Phe

370

Tyr Pro

Pro Glu 385

Asn Asn

Ser Phe

Phe Leu

Glu Gly

Asn Val

420

His Tyr

Thr Gln 435

Gly Leu 325

Pro Arg

Thr Lys

Ser Asp

Tyr Lys 390

Tyr Ser 405

Phe Ser

Lys Ser

Pro Ser

Glu Pro

Asn Gln

360

Ile Ala

375

Thr Thr

Arg Leu

Cys Ser

Leu Ser

440

Ser Ile

330

Gln Val 345

Val Ser

Val Glu

Pro Pro

Thr Val

410

ValMet 425

Leu Ser <210> 162 <211> 1344 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 162 caggtgcagc tcctgcaagg cctggacaag gcacagaagt atggagctga atttttggag tcagcctcca gagagcacag tcgtggaact tcaggactct acctacacct tggtgcagtc cttctggata ggcttgagtg ttcagggcag gcaggctgag tgg ttacctg ccaagggccc ccgccctggg caggcgccct actccctcag gcaacgtaga tggggctgag caccttcatt gatgggatgg ggtcaccatg atctgacgac gttcgacccc atcggtcttc ctgcctggtc gaccagcggc cagcgtggtg tcacaagccc

Glu Lys

Tyr Thr

Leu Thr

Trp Glu

380

Val Leu 395

Asp Lys

His Glu

Leu Gly gtgaagaagc aactactata atcaacccta accagggaca acggccgtgt tggggccagg cccctggcgc aaggactact gtgcacacct accgtgccct agcaacacca

Thr Ile

Leu Pro

350

Cys Leu 365

Ser Asn

Asp Ser

Ser Arg

Ala Leu

430

Lys

445 ctggggcctc tacactgggt acagtggtgg cgtccatcag attactgtgc gaaccctggt cctgctccag tccccgaacc tcccggctgt ccagcagctt aggtggacaa

Ser Lys 335

Pro Ser

Val Lys

Gly Gln

Asp Gly 400

Trp Gln 415

His Asn agtgaaggtc gcgacaggcc cacaaactat cacagcctac gattattacg caccgtctcc gagcacctcc ggtgacggtg cctacagtcc gggcacgaag gagagttgag

120

180

240

300

360

420

480

540

600

660

- 234 044746

tccaaatatg gtcccccatg cccaccgtgc ccagcaccag gcggtggcgg accatcagtc ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg tgcgtggtgg tggacgtgag caggaagac cccgaggtcc agttcaactg gtacgtggat ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaacggcaa ggagtacaag tgcaaggtct ccaacaaagg cctcccgtcc tccatcgaga aaaccatctc caaagccaaa gggcagcccc gagagccaca ggtgtacacc ctgcccccat cccaggagga gatgaccaag aaccaggtca gcctgacctg cctggtcaaa ggcttctacc ccagcgacat cgccgtggag tggggagagca atggggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc gacggctcct tcttcctcta cagcaggctc accgtggac agagcaggtg gcaggagggg aatgtcttct catgctccgt gatgcatgag gctctgcaca accactacac acagaagtcc ctctccctgt ctctggggtaa atga

<210> 163 <211> 447 <212> PROTEIN <213> Artificial sequence

720

780

840

900

960

1020

1080

1140

1200

1260

1320

1344 <220>

<223> Synthetic <400> 163

Gln Val 1

Gln Leu

Val Gln 5

Ser Gly

Ala Glu

Val Lys

Lys Pro

Ser Val

Lys Val 20

Ser Cys

Lys Ala

Ser Gly 25

Tyr Thr

Phe Ile

Tyr Ile

His Trp 35

Val Arg

Gln Ala

Pro Gly

Gln Gly

Leu Glu 45

Gly Trp 50

Ile Asn

Pro Asn

Ser Gly 55

Gly Thr

Asn Tyr

Ala Gln

Gln Gly 65

Arg Val

Thr Met

Thr Arg

Asp Thr

Ser Ile 75

Ser Thr

Met Glu

Leu Ser

Arg Leu 85

Arg Ser

Asp Asp

Thr Ala

Val Tyr

Ala Ile

Ile Thr

100

Ile Phe

Gly Val

Val Thr 105

Trp Phe

Asp Pro

110

Gly Ala 15

Asn Tyr

Trp Met

Lys Phe

Ala Tyr 80

Tyr Cys 95

Trp Gly

- 235 044746

Gln Gly Thr Leu Val 115

Thr Val Ser Ser Ala

120

Ser Thr Lys Gly Pro

125

Val Phe Pro Leu Ala

130

Pro Cys Ser Arg Ser

135

Thr Ser Glu Ser Thr

140

Ala Leu Gly Cys Leu 145

Val Lys Asp Tyr Phe 150

Pro Glu Pro Val Thr 155

Ser Trp Asn Ser Gly

165

Ala Leu Thr Ser Gly

170

Val His Thr Phe Pro

175

Val Leu Gln Ser Ser

180

Gly Leu Tyr Ser Leu

185

Ser Ser Val Val Thr

190

Pro Ser Ser Ser Leu

195

Gly Thr Lys Thr Tyr 200

Thr Cys Asn Val Asp

205

Lys Pro Ser Asn Thr

210

Lys Val Asp Lys Arg

215

Val Glu Ser Lys Tyr

220

Pro Pro Cys Pro Pro 225

Cys Pro Ala Pro Gly 230

Gly Gly Gly Pro Ser 235

Phe Leu Phe Pro Pro

245

Lys Pro Lys Asp Thr

250

Leu Met Ile Ser Arg

255

Pro Glu Val Thr Cys

260

Val Val Val Asp Val

265

Ser Gln Glu Asp Pro

270

Val Gln Phe Asn Trp

275

Tyr Val Asp Gly Val

280

Glu Val His Asn Ala

285

Thr Lys Pro Arg Glu

290

Glu Gln Phe Asn Ser

295

Thr Tyr Arg Val Val

300

Val Leu Thr Val Leu 305

His Gln Asp Trp Leu 310

Asn Gly Lys Glu Tyr 315

Cys Lys Val Ser Asn

325

Lys Gly Leu Pro Ser

330

Ser Ile Glu Lys Thr

335

Ser Lys Ala Lys Gly

340

Gln Pro Arg Glu Pro

345

Gln Val Tyr Thr Leu

350

Pro Ser Gln Glu Glu

355

Met Thr Lys Asn Gln 360

Val Ser Leu Thr Cys 365

Ser

Ala

Val 160

Ala

Val

His

Gly

Val 240

Thr

Glu

Lys

Ser

Lys 320

Ile

Pro

Leu

- 236 044746

Val Lys Gly Phe Tyr Pro Ser Asp

370 375

Ile Ala Val Glu Trp Glu Ser Asn

380

Gly Gln Pro Glu Asn Asn Tyr Lys

385 390

Thr Thr Pro Pro Val Leu Asp Ser

395 400

Asp Gly Ser Phe Phe Leu Tyr Ser 405

Arg Leu Thr Val Asp Lys Ser Arg

410 415

Trp Gln Glu Gly Asn Val Phe Ser 420

Cys Ser Val Met His Glu Ala Leu

425 430

His Asn His Tyr Thr Gln Lys Ser

435 440

Leu Ser Leu Ser Leu Gly Lys

445 <210> 164 <211> 1326 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 164 caggtgcagc tgcaggagtc ggggccagga ctggtgaagc cttcggagac cctgtccctc 60 acctgcactg tctctggtgg ctccacatcagt agtactact ggagttggat ccggcagccc 120 ccagggaagg gactggagtg gattggggtat atctattaca gtgggagcac caactacaac 180 ccctccctca agagtcgagt caccatatca gtagacacgt ccaagaacca gttctccctg 240 aaactgagct ctgtgaccgc tgcggacacg gccgtgtatt actgtgcgag agacccgctc 300 ctcattgact actggggcca gggaaccctg gtcaccgtct cctcagcctc caccaagggc 360 ccatcggtct tccccctggc gccctgctcc aggagcacct ccgagagcac agccgccctg 420 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540 agcagcgtgg tgaccgtgcc ctccagcagc ttggggcacga agacctacac ctgcaacgta 600 gatcacaagc ccagcaacac caaggtggac aagagagttg agtccaaata tggtccccca 660 tgccaccgt gccagcacc aggcggtggc ggaccatcag tcttcctgtt ccccccaaaa 720 cccaaggaca ctctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 780 agccaggaag accccgaggt ccagttcaac tggtacgtgg atggcgtgga ggtgcataat 840 gccaagacaa agccgcggga ggagcagttc aacagcacgt accgtgtggt cagcgtcctc 900 accgtcctgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 960

- 237 044746

ggcctcccgt cctccatcga gaaaaccatc tccaaagcca aagggcagcc ccgagagcca 1020 caggtgtaca ccctgccccc atcccaggag gagatgacca agaaccaggt cagcctgacc 1080 tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agggggagag caatggggcag 1140 ccggagaaca actacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc 1200 tacagcaggc tcaccgtgga caagagcagg tggcaggagg ggaatgtctt ctcatgctcc 1260 gtgatgcatg aggctctgca caaccactac acacagaagt ccctctccct gtctctggggt 1320

aaatga

1326 <210> 165 <211> 441 <212> PROTEIN <213> Artificial sequence <220>

< 223 > Synthetic < 400 > 165

Gln Val 1

Gln Leu Gln Glu Ser Gly Pro 5

Gly Leu Val Lys Pro Ser Glu

15

Thr Leu

Ser Leu Thr Cys Thr Val Ser

25

Gly Gly Ser Ile Ser Ser Tyr 30

Tyr Trp

Ser Trp Ile Arg Gln Pro Pro

40

Gly Lys Gly Leu Glu Trp Ile 45

Gly Tyr 50

Ile Tyr Tyr

Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys

60

Ser Arg Val Thr Ile 65

Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu

75 80

Lys Leu Ser Ser Val 85

Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 90 95

Arg Asp Pro Leu Leu

100

Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr

105 110

Val Ser Ser Ala Ser

115

Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro

120 125

Cys Ser Arg Ser Thr 130

Ser Glu Ser

135

Lys Asp Tyr Phe Pro 145

Glu Pro Val 150

Thr Ala Ala Leu Gly Cys Leu Val 140

Thr Val Ser Trp Asn Ser Gly Ala 155 160

- 238 044746

Leu

Leu

Thr

Val

Pro 225

Pro

Val

Val

Gln

Gln 305

Gly

Pro

Thr

Ser

Tyr 385

Tyr

Thr Ser Gly

Tyr Ser Leu

180

Lys Thr Tyr

195

Asp Lys Arg 210

Ala Pro Gly

Lys Asp Thr

Val Asp Val

260

Asp Gly Val

275

Phe Asn Ser 290

Asp Trp Leu

Leu Pro Ser

Arg Glu Pro

340

Lys Asn Gln

355

Asp Ile Ala 370

Lys Thr Thr

Ser Arg Leu

Val His Thr 165

Ser Ser Val

Thr Cys Asn

Val Glu Ser

215

Gly Gly Gly

230

Leu Met Ile 245

Ser Gln Glu

Glu Val His

Thr Tyr Arg

295

Asn Gly Lys

310

Ser Ile Glu 325

Gln Val Tyr

Val Ser Leu

Val Glu Trp

375

Pro Pro Val

390

Thr Val Asp

Phe Pro Ala

170

Val Thr Val

185

Val Asp His 200

Lys Tyr Gly

Pro Ser Val

Ser Arg Thr

250

Asp Pro Glu

265

Asn Ala Lys 280

Val Val Ser

Glu Tyr Lys

Lys Thr Ile

330

Thr Leu Pro

345

Thr Cys Leu 360

Glu Ser Asn

Leu Asp Ser

Lys Ser Arg

Val Leu Gln

Pro Ser Ser

Lys Pro Ser

205

Pro Pro Cys

220

Phe Leu Phe 235

Pro Glu Val

Val Gln Phe

Thr Lys Pro

285

Val Leu Thr

300

Cys Lys Val 315

Ser Lys Ala

Pro Ser Gln

Val Lys Gly

365

Gly Gln Pro

380

Asp Gly Ser 395

Trp Gln Glu

Ser Ser Gly

175

Ser Leu Gly 190

Asn Thr Lys

Pro Pro Cys

Pro Pro Lys

240

Thr Cys Val

255

Asn Trp Tyr 270

Arg Glu Glu

Val Leu His

Ser Asn Lys

320

Lys Gly Gln

335

Glu Glu Met 350

Phe Tyr Pro

Glu Asn Asn

Phe Phe Leu

400

Gly Asn Val

- 239 044746

405 410415

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln 420 425430

Lys Ser Leu Ser Leu Ser Leu Gly Lys

435440 <210>

<211>

<212>

<213>

166

375

DNA

Artificial sequence <220>

<223> Synthetic <400> 166 gaagtgcagc tcctgtgcag ccagggaagg gcggactctg ctgcaaatga gactggaact gtcaccgtct tggtggagtc cctctggatt gcctggagtg tgaagggccg acagtctgag cgagaggtta cctca tgggggaggc cacctttgat ggtctca ggt attcaccatc agctgcggac ctactactac ttggtacagc gattatgcca attagttgga tccagagaca acggccttgt ggtatggacg ctggcaggtc tgtactgggt atagtggtag acgccaagaa attactgtgc tctggggcca cctgagactc ccggcaagct cataggctat ctccctgtat aaaagataa agggaccacg

120

180

240

300

360

375 <210> 167 <211> 125 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 167

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Asp Asp Tyr 25 30

Ala Met Tyr Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Gly Ile Ser Trp Asn Ser Gly

55

Ser Ile Gly Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ala Lys Asn Ser Leu Tyr

80

- 240 044746

Leu Gln Met Asn Ser Leu Arg Ala 85

Ala Asp Thr Ala 90

Leu

Tyr Tyr Cys 95

Ala Lys Asp Lys Asp Trp Asn Ser

100

Arg Gly Tyr Tyr 105

Tyr Tyr Gly Met 110

Asp Val Trp Gly Gln Gly Thr Thr

115 120

Val Thr Val Ser

Ser

125 <210> 168 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 168 ggattcacct ttgatgatta tgcc <210> 169 <211> 8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 169

Gly Phe Thr Phe Asp Asp Tyr Ala

5 <210> 170 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 170 attagttgga atagtggtag cata <210> 171 <211> 8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 171

Ile Ser Trp Asn Ser Gly Ser Ile

- 241 044746 <210> 172 <211> 54 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>172 gcaaaagata aagactggaa ctcgagaggt tactactact acggtatgga cgtc54 <210>173 <211>18 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>173

Ala Lys Asp Lys Asp Trp Asn Ser Arg Gly Tyr Tyr Tyr Tyr Gly Met

5 1015

Asp Val <210>174 <211>321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 174

gatgttgtga tgaccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180 aggttcagtg gcagtggatc tggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagatttg caactacta ctgtcaacag agtacatta ctccgtacac ttttggccag 300 gggaccaagg tggagatcaa a 321

<210> 175 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic

- 242 044746 <400>175

Asp Val Val Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ile Thr Pro Tyr 85 9095

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100105 <210>176 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>176 caacagagtt acattactcc gtacact <210>177 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>177

Gln Gln Ser Tyr Ile Thr Pro Tyr Thr <210>178 <211>1368 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

- 243 044746

<400> 178 gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttgat gattatgcca tgtactgggt ccggcaagct 120 ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180 gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240 ctgcaaatga acagtctgag agctgcggac acggccttgt attackgtgc aaaagataaa 300 gactggaact cgagaggtta ctactactac ggtatggacg tctggggcca agggaccacg 360 gtcaccgtct cctcagcctc caccaagggc ccatcggtct tccccctggc accctcctcc 420 aagagcacct ctggggggcac agcggccctg ggctgcctgg tcaaggacta cttccccgaa 480 ccggtgacgg tgtcgtggaa ctcaggcgcc ctgaccagcg gcgtgcacac cttcccggct 540 gtcctacagt cctcaggact ctactccctc agcagcgtgg tgaccgtgcc ctccagcagc 600 ttggggcaccc agacctacat ctgcaacgtg aatcacaagc ccagcaacac caaggtggac 660 aagaaagttg agcccaaatc ttgtgacaaa actcacacat gccaccgtg cccagcacct 720 gaactcctgg ggggaccgtc agtcttcctc ttccccccaa aacccaagga caccctcatg 780 atctcccgga cccctgaggt cacatgcgtg gtggtggacg tgagccacga agaccctgag 840 gtcaagttca actggtacgt ggacggcgtg gaggtgcata atgccaagac aaagccgcgg 900 gagggagt acaacagcac gtaccgtgtg gtcagcgtcc tcaccgtcct gcaccaggac 960 tggctgaatg gcaagggagta caagtgcaag gtctccaaca aagccctccc agcccccatc 1020 gagaaaacca tctccaaagc caaagggcag ccccgagaac cacaggtgta caccctgccc 1080 ccaccccgggg atgagctgac caagaaccag gtcagcctga cctgcctggt caaaggcttc 1140 tatcccagcg acatcgccgt ggagtggggag agcaatggggc agccggagaa caactacaag 1200 accacgcctc ccgtgctgga ctccgacggc tccttcttcc tctacagcaa gctcaccgtg 1260 gacaagagca ggtggcagca ggggaacgtc ttctcatgct ccgtgatgca tgaggctctg 1320 cacaaccact acacgcagaa gtccctctcc ctgtctccgg gtaaatga 1368

<210> 179 <211> 455 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 179

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

5 10 15

- 244 044746

Ser

Ala

Ser

Lys 65

Leu

Ala

Asp

Lys

Gly 145

Pro

Thr

Val

Asn

Pro 225

Glu

Asp

Leu Arg Leu Ser Cys 20

Met Tyr Trp Val Arg 35

Gly Ile Ser Trp Asn 50

Gly Arg Phe Thr Ile 70

Gln Met Asn Ser Leu

Lys Asp Lys Asp Trp

100

Val Trp Gly Gln Gly 115

Gly Pro Ser Val Phe 130

Gly Thr Ala Ala Leu

150

Val Thr Val Ser Trp

165

Phe Pro Ala Val Leu

180

Val Thr Val Pro Ser

195

Val Asn His Lys Pro 210

Lys Ser Cys Asp Lys

230

Leu Leu Gly Gly Pro

245

Thr Leu Met Ile Ser

260

Ala Ala Ser Gly Phe 25

Gln Ala Pro Gly Lys 40

Ser Gly Ser Ile Gly 55

Ser Arg Asp Asn Ala 75

Arg Ala Ala Asp Thr

Asn Ser Arg Gly Tyr 105

Thr Thr Val Thr Val

120

Pro Leu Ala Pro Ser 135

Gly Cys Leu Val Lys

155

Asn Ser Gly Ala Leu

170

Gln Ser Ser Gly Leu 185

Ser Ser Leu Gly Thr

200

Ser Asn Thr Lys Val 215

Thr His Thr Cys Pro

235

Ser Val Phe Leu Phe

250

Arg Thr Pro Glu Val

265

Thr Phe Asp Asp Tyr 30

Gly Leu Glu Trp Val 45

Tyr Ala Asp Ser Val 60

Lys Asn Ser Leu Tyr 80

Ala Leu Tyr Tyr Cys 95

Tyr Tyr Tyr Gly Met 110

Ser Ser Ala Ser Thr

125

Ser Lys Ser Thr Ser 140

Asp Tyr Phe Pro Glu

160

Thr Ser Gly Val His 175

Tyr Ser Leu Ser Ser 190

Gln Thr Tyr Ile Cys

205

Asp Lys Lys Val Glu 220

Pro Cys Pro Ala Pro

240

Pro Pro Lys Pro Lys

255

Thr Cys Val Val Val

270

- 245 044746

Asp Val

Gly Val

290

Asn Ser 305

Trp Leu

Ser His 275

Glu Val

Thr Tyr

Asn Gly

Glu Asp

His Asn

Arg Val

310

Lys Glu 325

Pro Ala

Pro Ile

340

Glu Lys

Glu Pro

Gln Val 355

Tyr Thr

Pro Glu

280

Ala Lys 295

Val Ser

Tyr Lys

Thr Ile

Leu Pro

360

Val Lys

Thr Lys

Val Leu

Cys Lys

330

Ser Lys 345

Pro Ser

Phe Asn

Pro Arg

300

Thr Val 315

Val Ser

Ala Lys

Arg Asp

Asn Gln

370

Val Ser

Leu Thr

Cys Leu 375

Val Lys

Gly Phe

380

Ile Ala

385

Val Glu

Trp Glu

390

Ser Asn

Gly Gln

Pro Glu 395

Thr Thr

Pro Pro

Val Leu 405

Asp Ser

Asp Gly

410

Ser Phe

Lys Leu

Thr Val

420

Asp Lys

Ser Arg

Trp Gln 425

Gln Gly

Cys Ser

ValMet 435

His Glu

Ala Leu

440

His Asn

His Tyr

Trp Tyr 285

Glu Glu

Leu His

Asn Lys

Gly Gln

350

Glu Leu 365

Tyr Pro

Asn Asn

Phe Leu

Asn Val

430

Thr Gln 445

Val Asp

Gln Tyr

Gln Asp

320

Ala Leu 335

Pro Arg

Thr Lys

Ser Asp

Tyr Lys

400

Tyr Ser 415

Phe Ser

Lys Ser

Leu Ser Leu Ser Pro Gly Lys

450455 <210>180 <211>645 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic <400> 180 gatgttgtga tgacccagtc tccatcctcc atcacttgcc gggcaagtca gagcattagc gggaaagccc ctaagctcct gatctatgct ctgtctgcat ctgtaggaga cagagtcacc agctatttaa attggtatca gcagaaacca gcatccagtt tgcaa agtgg ggtcccatca

120

180

- 246 044746 aggttcagtg gaagattttg gggaccaagg tctgatgagc cccagagagg gagagtgtca ctgagcaaag ctgagctcgc gcagtggatc caacttacta tggagatcaa agttgaaatc ccaaagtaca cagagcagga cagactacga ccgtcacaaa tgggac agat ctgtcaacag acgaactgtg tggaactgcc gtggaaggtg cagcaaggac gaaacacaaa gagcttcaac ttcactctca agttacatta gctgcaccat tctgttgtgt gataacgccc agcacctaca gtctacgcct aggggagagt ccatcagcag ctccgtacac ctgtcttcat gcc tgctgaa tccaatcggg gcctcagcag gcgaagtcac gttag tctgcaacct ttttggccag cttcccgcca taacttctat taactcccag caccctgacg ccatcagggc

240

300

360

420

480

540

600

645 <210> 181 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 181

Asp Val 1

Val Met

Thr Gln 5

Ser Pro

Ser Ser

Leu Ser

Ala Ser

Asp Arg

Val Thr

Ile Thr

CysArg

Ala Ser 25

Gln Ser

Ile Ser

Leu Asn

Trp Tyr 35

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

Lys Leu 45

Tyr Ala 50

Ala Ser

Ser Leu

Gln Ser 55

Gly Val

Pro Ser

Arg Phe

Ser Gly 65

Ser Gly

Thr Asp 70

Phe Thr

Leu Thr

Ile Ser 75

Ser Leu

Glu Asp

Phe Ala

Thr Tyr 85

Tyr Cys

Gln Gln

Ser Tyr

Ile Thr

Thr Phe

Gly Gln

100

Gly Thr

Lys Val

Glu Ile 105

Lys Arg

Thr Val

110

Pro Ser

Val Phe

115

Ile Phe

Pro Pro

120

Ser Asp

Glu Gln

Leu Lys 125

Thr Ala

130

Ser Val

Val Cys

Leu Leu 135

Asn Asn

Phe Tyr

140

Pro Arg

Val Gly 15

Ser Tyr

Leu Ile

Ser Gly

Glin Pro 80

Pro Tyr 95

Ala Ala

Ser Gly

Glu Ala

- 247 044746

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

145 150155

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

165170

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

180185

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

195200

Ser Gly Asn Ser Gln

160

Thr Tyr Ser Leu Ser

175

Lys His Lys Val Tyr 190

Pro Val Thr Lys Ser

205

Phe Asn Arg Gly Glu Cys

210

<210> 182 <211> 1356 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 182 gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttgat gattatgcca tgtactgggt ccggcaagct 120 ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180 gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240 ctgcaaatga acagtctgag agctgcggac acggccttgt attackgtgc aaaagataaa 300 gactggaact cgagaggtta ctactactac ggtatggacg tctggggcca agggaccacg 360 gtcaccgtct cctcagcctc caccaagggc ccatcggtct tccccctggc gccctgctcc 420 aggagcacct ccgagagcac agccgccctg ggctgcctgg tcaaggacta cttccccgaa 480 ccggtgacgg tgtcgtggaa ctcaggcgcc ctgaccagcg gcgtgcacac cttcccggct 540 gtcctacagt cctcaggact ctactccctc agcagcgtgg tgaccgtgcc ctccagcagc 600 ttggggcacga agacctacac ctgcaacgta gatcacaagc ccagcaacac caaggtggac 660 aagagagttg agtccaaata tggtccccca tgccaccgt gccagcacc aggcggtggc 720 ggaccatcag tcttcctgtt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc 780 cctgaggtca cgtgcgtggt ggtggacgtg agccaggaag accccgaggt ccagttcaac 840 tggtacgtgg atggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagttc 900 aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaacggc 960 aaggagtaca agtgcaaggt ctccaacaaa ggcctcccgt cctccatcga gaaaaccatc 1020

- 248 044746 tccaaagcca gagatgacca atcgccgtgg gtgctggact tggcaggagg acacagaagt aagggcagcc agaaccaggt agtgggag ccgacggctc ggaatgtctt ccctctccct ccgagagcca cagcctgacc caatgggcag cttcttcctc ctcatgctcc gtctctgg gt caggtgtaca tgcctggtca ccggagaaca tacagcaggc gtgatgcatg aaatga ccctgccccc aaggcttcta actacaagac tcaccgtgga aggctctgca atcccaggag ccccagcgac cacgcctccc caagagcagg caaccactac

1080

1140

1200

1260

1320

1356 <210> 183 <211> 451 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic <400> 183

Glu Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly

Leu Val

Glin Pro

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Phe Thr

Phe Asp 30

Ala Met

Tyr Trp 35

Val Arg

Gln Ala

Pro Gly

Lys Gly

Leu Glu 45

Ser Gly 50

Ile Ser

Trp Asn

Ser Gly 55

Ser Ile

Gly Tyr 60

Ala Asp

Lys Gly 65

Arg Phe

Thr Ile

Ser Arg

Asp Asn

Ala Lys 75

Asn Ser

Leu Gln

Met Asn

Ser Leu 85

Arg Ala

Ala Asp

Thr Ala

Leu Tyr

Ala Lys

Asp Lys

100

Asp Trp

Asn Ser

Arg Gly 105

Tyr Tyr

Tyr Tyr

110

Asp Val

Trp Gly 115

Gln Gly

Thr Thr

120

Val Thr

Val Ser

Ser Ala 125

Lys Gly

130

Pro Ser

Val Phe

Pro Leu 135

Ala Pro

Cys Ser

140

Arg Ser

Glu Ser 145

Thr Ala

Ala Leu

150

Gly Cys

Leu Val

Lys Asp 155

Tyr Phe

Gly Arg 15

Asp Tyr

Trp Val

Ser Val

Leu Tyr 80

Tyr Cys 95

Gly Met

Ser Thr

Thr Ser

Pro Glu

160

- 249 044746

Pro

Thr

Val

Asn

Ser 225

Gly

Ile

Glu

His

Arg 305

Lys

Glu

Tyr

Leu

Trp 385

Val

Val Thr Val

Phe Pro Ala

180

Val Thr Val

195

Val Asp His 210

Lys Tyr Gly

Pro Ser Val

Ser Arg Thr

260

Asp Pro Glu

275

Asn Ala Lys 290

Val Val Ser

Glu Tyr Lys

Lys Thr Ile

340

Thr Leu Pro

355

Thr Cys Leu 370

Glu Ser Asn

Leu Asp Ser

Ser Trp Asn 165

Val Leu Gln

Pro Ser Ser

Lys Pro Ser

215

Pro Pro Cys

230

Phe Leu Phe 245

Pro Glu Val

Val Gln Phe

Thr Lys Pro

295

Val Leu Thr

310

Cys Lys Val 325

Ser Lys Ala

Pro Ser Gln

Val Lys Gly

375

Gly Gln Pro

390

Asp Gly Ser 405

Ser Gly Ala

170

Ser Ser Gly

185

Ser Leu Gly 200

Asn Thr Lys

Pro Pro Cys

Pro Pro Lys

250

Thr Cys Val

265

Asn Trp Tyr 280

Arg Glu Glu

Val Leu His

Ser Asn Lys

330

Lys Gly Gln

345

Glu Glu Met 360

Phe Tyr Pro

Glu Asn Asn

Phe Phe Leu

410

Leu Thr Ser

Leu Tyr Ser

Thr Lys Thr

205

Val Asp Lys

220

Pro Ala Pro 235

Pro Lys Asp

Val Val Asp

Val Asp Gly

285

Gln Phe Asn

300

Gln Asp Trp 315

Gly Leu Pro

Pro Arg Glu

Thr Lys Asn

365

Ser Asp Ile

380

Tyr Lys Thr 395

Tyr Ser Arg

Gly Val His 175

Leu Ser Ser 190

Tyr Thr Cys

Arg Val Glu

Gly Gly Gly

240

Thr Leu Met

255

Val Ser Gln 270

Val Glu Val

Ser Thr Tyr

Leu Asn Gly

320

Ser Ser Ile

335

Pro Gln Val 350

Gln Val Ser

Ala Val Glu

Thr Pro Pro

400

Leu Thr Val

415

- 250 044746

Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met

420

425

430

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

435

440

445

Leu Gly Lys

450 <210> 184 <211> 348 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>184 gaggtgcagc tggtggagtc tggaggaggc ttggtccagt ctggggggtc cctgagactc60 tcctgtgcag cctctgggct caccgtcagt agcaactaca tgagctgggt ccgccaggct120 ccagggaagg gactggagtg ggtctcagtt atttatagcg gtggtagcac attctactca180 gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agcgagggga300 gacgcttttg atatctgggg ccaagggaca atggtc accg tctcttca348 <210>185 <211> 116 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 185

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ser Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Leu Thr Val Ser Ser Asn

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ser Asp Ser Val Lys

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu

- 251 044746

Gln Met Asn Ser

Arg Ala Arg Gly 100

Thr Val Ser Ser 115

Leu Arg Ala Glu 85

Asp Ala Phe Asp

Asp Thr Ala Val 90

Ile Trp Gly Gln 105

Tyr Tyr Cys Ala 95

Gly Thr Met Val 110 <210> 186 <211> 24 <212> DNA <213> Artificial Sequence <220>

<223> Synthetic <400>186 gggctcaccg tcagtagcaa ctac <210>187 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>187

Gly Leu Thr Val Ser Ser Asn Tyr <210>188 <211>30 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>188 gcgagagcga ggggagacgc ttttgatatc <210>189 <211>10 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 189

- 252 044746

Ala Arg Ala Arg Gly Asp Ala Phe Asp Ile 1,510 <210>190 <211>324 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 190

gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtggggaga cagagtcacc 60 atcacttgcc aggcgagtca gggcattagc aactatttaa attggtatca gcagaaacca 120 gggaaagccc ctaaactcct gatctccgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaggatattg caacatatta ctgtcaacag tatgataatc tccgcttttt cactttcggc 300 cctggacca aagtggatat caaa 324

<210> 191 <211> 108 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>191

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Gly Ile Ser Asn Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Ser Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Arg Phe 85 9095

Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100105

- 253 044746 <210> 192 <211> 18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>192 cagggcatta gcaactat18

<210> 193 <211> 9 <212> DNA <213> Artificial sequence <220> <223> Synthetic <400> 193

gatgcatcc <210>194 <211>3 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>194

Asp Ala Ser <210>195 <211>30 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>195 caacagtatg ataatctccg ctttttcact <210>196 <211>10 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 196

Gln Gln Tyr Asp Asn Leu Arg Phe Phe Thr

5 10

- 254 044746 <210> 197 <211> 1341 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>197 gaggtgcagc tggtggagtc tggaggaggc ttggtccagt ctggggggtc cctgagactc60 tcctgtgcag cctctgggct caccgtcagt agcaactaca tgagctgggt ccgccaggct120 ccagggaagg gactggagtg ggtctcagtt atttatagcg gtggtagcac attctactca180 gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agcgagggga300 gacgcttttg atatctgggg ccaagggaca atggtc accg tctcttcagc ctccaccaag360 ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc420 ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc480 gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc540 ctcagcagcg tggtgaccgt gccctccagc agcttgggca cccagaccta catctgcaac 600 gtgaatcaca agcccagcaa caccaaggtg gacaagaaag ttgagcccaa atcttgtgac660 aaaactcaca catgcccacc gtgcccagca cctgaactcc tggggggacc gtcagtcttc720 ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc7 80 gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc840 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cacgtaccgt900 gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc960 aaggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg1020 cagccccgag aaccacaggt gtacaccctg cccccatccc gggatgagct gaccaagaac1080 caggtcagcc tgacctgcct ggtca aaggc ttctatccca gcgacatcgc cgtggagtgg1140 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac1200 ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac1260 gtcttctcat gctccgtga t gcatgaggct ctgcacaacc actacacgca gaagtccctc1320 tccctgtctc cgggtaaatg a1341 <210>198 <211> 446 <212> PROTEIN <213> Artificial sequence

- 255 044746 <220>

<223>

Synthetic <400>

198

Glu 1

Val

Gln

Leu

Val 5

Glu

Ser

Gly

Gly

Gly 10

Leu

Val

Gln

Ser

Gly 15

Ser

Leu

Arg

Leu 20

Ser

Cys

Ala

Ala

Ser 25

Gly

Leu

Thr

Val

Ser 30

Ser

Tyr

Met

Ser 35

Trp

Val

Arg

Gln

Ala 40

Pro

Gly

Lys

Gly

Leu 45

Glu

Trp

Ser

Val 50

Ile

Tyr

Ser

Gly

Gly 55

Ser

Thr

Phe

Tyr

Ser 60

Asp

Ser

Val

Gly 65

Arg

Phe

Thr

Ile

Ser 70

Arg

His

Asn

Ser

Lys 75

Asn

Thr

Leu

Tyr

Gln

Met

Asn

Ser

Leu 85

Arg

Ala

Glu

Asp

Thr 90

Ala

Val

Tyr

Tyr

Cys 95

Arg

Ala

Arg

Gly 100

Asp

Ala

Phe

Asp

Ile

105

Trp

Gly

Gln

Gly

Thr

110

Met

Thr Val Ser Ser Ala

115

Ser Thr Lys Gly Pro 120

Ser Val Phe Pro Leu

125

Pro Ser Ser Lys Ser 130

Thr Ser Gly Gly Thr

135

Ala Ala Leu Gly Cys 140

Val Lys Asp Tyr Phe 145

Pro Glu Pro Val Thr 150

Val Ser Trp Asn Ser 155

Ala Leu Thr Ser Gly

165

Val His Thr Phe Pro

170

Ala Val Leu Gln Ser

175

Gly Leu Tyr Ser Leu

180

Ser Ser Val Val Thr

185

Val Pro Ser Ser Ser

190

Gly Thr Gln Thr Tyr 195

Ile Cys Asn Val Asn

200

His Lys Pro Ser Asn

205

Lys Val Asp Lys Lys

210

Val Glu Pro Lys Ser

215

Cys Asp Lys Thr His

220

Cys Pro Pro Cys Pro 225

Ala Pro Glu Leu Leu 230

Gly Gly Pro Ser Val 235

Gly

Asn

Val

Lys

Leu 80

Ala

Val

Ala

Leu

Gly 160

Ser

Leu

Thr

Thr

Phe 240

- 256 044746

Leu Phe Pro Pro Lys

245

Pro Lys Asp Thr Leu

250

Met Ile Ser Arg Thr

255

Glu Val Thr Cys Val

260

Val Val Asp Val Ser

265

His Glu Asp Pro Glu

270

Lys Phe Asn Trp Tyr

275

Val Asp Gly Val Glu

280

Val His Asn Ala Lys

285

Lys Pro Arg Glu Glu

290

Gln Tyr Asn Ser Thr

295

Tyr Arg Val Val Ser

300

Leu Thr Val Leu His 305

Gln Asp Trp Leu Asn 310

Gly Lys Glu Tyr Lys 315

Lys Val Ser Asn Lys

325

Ala Leu Pro Ala Pro

330

Ile Glu Lys Thr Ile

335

Lys Ala Lys Gly Gln

340

Pro Arg Glu Pro Gln

345

Val Tyr Thr Leu Pro

350

Ser Arg Asp Glu Leu

355

Thr Lys Asn Gln Val

360

Ser Leu Thr Cys Leu

365

Lys Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val

375

Glu Trp Glu Ser Asn

380

Gln Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro 390

Pro Val Leu Asp Ser 395

Gly Ser Phe Phe Leu

405

Tyr Ser Lys Leu Thr

410

Val Asp Lys Ser Arg

415

Gln Gln Gly Asn Val

420

Phe Ser Cys Ser Val

425

Met His Glu Ala Leu

430

Pro

Val

Thr

Val

Cys 320

Ser

Pro

Val

Gly

Asp 400

Trp

His

Asn His Tyr Thr Gln 435

Lys Ser Leu Ser Leu 440

Ser Pro Gly Lys

445 <210> 199 <211> 648 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 199

- 257 044746

gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtggggaga cagagtcacc 60 atcacttgcc aggcgagtca gggcattagc aactatttaa attggtatca gcagaaacca 120 gggaaagccc ctaaactcct gatctccgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaggatattg caacatatta ctgtcaacag tatgataatc tccgcttttt cactttcggc 300 cctggacca aagtggatat caaacgaact gtggctgcac catctgtctt catcttcccg 360 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420 tatccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 648

<210> 200 <211> 215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>200

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Gly Ile Ser Asn Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Ser Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Arg Phe 85 9095

Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg Thr Val Ala

100 105110

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

115 120125

- 258 044746

Gly Thr Ala Ser Val Val Cys Leu

130 135

Leu Asn Asn Phe Tyr Pro Arg Glu

140

Ala Lys Val Gln Trp Lys Val Asp

145 150

Asn Ala Leu Gln Ser Gly Asn Ser

155 160

Gln Glu Ser Val Thr Glu Gln Asp

165

Ser Lys Asp Ser Thr Tyr Ser Leu

170 175

Ser Ser Thr Leu Thr Leu Ser Lys 180

Ala Asp Tyr Glu Lys His Lys Val

185 190

Tyr Ala Cys Glu Val Thr His Gln

195 200

Gly Leu Ser Ser Pro Val Thr Lys

205

Ser Phe Asn Arg Gly Glu Cys

210 215 <210>

<211>

<212>

<213>

201

360

DNA

Artificial sequence <220>

<223> Synthetic <400> 201 caggtgcagc tcctgtgcag ccagggaagg gcagactctg ctgcaaatga ggtacaacta tggtggagtc cctctggatt ggctggagtg tgaagggccg acagcctgag tggtcccctt tgggggaggc caccttcagt ggtttcatac attcaccatc a gccgaggac tgactactgg ttggtcaagc gactactaca attacttata tccagggaca acggccgtgt ggccagggaa ctggagggtc tgagctggat gtggtagtac acgccaagag attactgtgc ccctggtcac cctgagactc ccgccaggct catatactac ctcactgtat gagagatcgc cgtctcctca

120

180

240

300

360 <210> 202 <211> 120 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 202

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr

- 259 044746

Tyr Met Ser Trp Ile Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Tyr Ile Thr Tyr Ser Gly Ser

55

Thr Ile Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ala Lys Ser Ser Leu Tyr

80

Leu Gln Met Asn Ser Leu Arg Ala 85

Glu Asp Thr Ala Val Tyr Tyr Cys

95

Ala Arg Asp Arg Gly Thr Thr Met

100

Val Pro Phe Asp Tyr Trp Gly Gln

105 110

Gly Thr Leu Val Thr Val Ser Ser

115120 <210>203 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>203 ggattcacct tcagtgacta ctac <210>204 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>204

Gly Phe Thr Phe Ser Asp Tyr Tyr <210>205 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 205 attacttata gtggtagtac cata

- 260 044746 <210> 206 <211> 8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>206

Ile Thr Tyr Ser Gly Ser Thr Ile <210>207 <211>39 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>207 gcgagagatc gcggtacaac tatggtcccc tttgactac <210>208 <211>13 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>208

Ala Arg Asp Arg Gly Thr Thr Met Val Pro Phe Asp Tyr

510 <210>209 <211>321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 209

gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc aggcgagtca ggacatacc aactatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctacgct gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccaccagcgg cctgcagcct 240 gaagatattg caacatatta ctgtcaacag tatgataatc tccctctcac tttcggcgga 300 gggaccaagg tggagatcaa a 321

- 261 044746 <210> 210 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>210

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Thr Asn Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Gly Leu Gln Pro 65 70 7580

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100105 <210>211 <211>18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>211 caggacatta ccaactat <210>212 <211>6 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 212

Gln Asp Ile Thr Asn Tyr 1 5

- 262 044746 <210> 213 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>213 caacagtatg ataatctccc tctcact27 <210>214 <211>9 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>214

Gln Gln Tyr Asp Asn Leu Pro Leu Thr <210>215 <211>1353 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 215 caggtgcagc tggtggagtc tgggggaggc ttggtcaagc ctggagggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagt gactactaca tgagctggat ccgccaggct 120 ccagggaagg ggctggagtg ggtttcatac attacktata gtggtagtac catatactac 180 gcagactctg tgaagggccg attcaccatc tccagggaca acgccaagag ctcactgtat 240 ctgcaaatga acagcctgag agccgaggac acggccgtgt attackgtgc gagagatcgc 300 ggtacaacta tggtcccctt tgactactgg ggccagggaa ccctggtcac cgtctcctca 360 gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacacc tcatgatctc ccggacccct 780

- 263 044746

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcggggaga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtacacc tgcccccatc ccgggatgag 1080 ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140 gccgtggagt ggggagagcaa tggggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1260 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320 cagaagtccc tctccctgtc tccggggtaaa tga 1353

<210> 216 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>216

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly 1 5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asp Tyr 20 2530

Tyr Met Ser Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Tyr Ile Thr Tyr Ser Gly Ser Thr Ile Tyr Tyr Ala Asp Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 9095

Ala Arg Asp Arg Gly Thr Thr Met Val Pro Phe Asp Tyr Trp Gly Gln

100 105110

Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120125

- 264 044746

Phe

Leu 145

Trp

Leu

Ser

Pro

Lys 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Pro Leu 130

Gly Cys

Asn Ser

Gln Ser

Ser Ser

195

Ser Asn

210

Thr His

Ser Val

Arg Thr

Pro Glu

275

Ala Lys 290

Val Ser

Tyr Lys

Thr Ile

Leu Pro

355

Cys Leu 370

Ala Pro

Leu Val

Gly Ala

165

Ser Gly 180

Leu Gly

Thr Lys

Thr Cys

Phe Leu

245

Pro Glu 260

Val Lys

Thr Lys

Val Leu

Cys Lys

325

Ser Lys 340

Pro Ser

Val Lys

Ser Ser

135

Lys Asp 150

Leu Thr

Leu Tyr

Thr Gln

Val Asp

215

Pro Pro 230

Phe Pro

Val Thr

Phe Asn

Pro Arg

295

Thr Val 310

Val Ser

Ala Lys

Arg Asp

Gly Phe

375

Lys Ser

Tyr Phe

Ser Gly

Ser Leu

185

Thr Tyr 200

Lys Lys

Cys Pro

Pro Lys

Cys Val

265

Trp Tyr 280

Glu Glu

Leu His

Asn Lys

Gly Gln

345

Glu Leu 360

Tyr Pro

Thr Ser

Pro Glu

155

Val His 170

Ser Ser

Ile Cys

Val Glu

Ala Pro

235

Pro Lys 250

Val Val

Val Asp

Gln Tyr

Gln Asp

315

Ala Leu 330

Pro Arg

Thr Lys

Ser Asp

Gly Gly 140

Pro Val

Thr Phe

Val Val

Asn Val

205

Pro Lys 220

Glu Leu

Asp Thr

Asp Val

Gly Val

285

Asn Ser 300

Trp Leu

Pro Ala

Glu Pro

Asn Gln

365

Ile Ala

380

Thr Ala

Thr Val

Pro Ala

175

Thr Val 190

Asn His

Ser Cys

Leu Gly

Leu Met

255

Ser His 270

Glu Val

Thr Tyr

Asn Gly

Pro Ile

335

Gln Val 350

Val Ser

Val Glu

Ala

Ser 160

Val

Pro

Lys

Asp

Gly 240

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

Leu

Trp

- 265 044746

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr

385 390

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr

405 410

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe

420 425

Glu Ala Leu His Asn His Tyr Thr Gln Lys

435 440

Lys 395 Thr Thr Pro Pro Val 400 Ser Lys Leu Thr Val 415 Asp Ser Cys Ser Val 430 Met His Ser Leu Ser 445 Leu Ser Pro

Gly Lys

450 <210> 217 <211> 645 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 217 gacatccaga atcacttgcc gggaaagccc aggttcagtg gaagatattg gggaccaagg tctgatgagc cccagagagg gagagtgtca ctgagcaaag ctgagctcgc tgacccagtc aggcgagtca ctaagctcct gaagtggatc caacatatta t ggagatcaa agttgaaatc ccaaagtaca cagagcagga cagactacga ccgtcacaaa tccatcctcc ggacattacc gatctacgct tgggacagat ctgtcaacag acgaactgtg tggaactgcc gtggaaggtg cagcaaggac gaaacacaaa gagcttcaac ctgtctgcat aactatttaa gcatcca att tttactttca tatgataatc gctgcaccat tctgttgtgt gataacgccc agcacctaca gtctacgcct aggggagagt ctgtaggaga attggtatca tggaaacagg ccatcagcgg tccctctcac ctgtcttcat gcctgctgaa tccaatcggg gcctcagcag gcgaagtcac gttag cagagtcacc gcagaaacca ggtcccatca cctgcagcct tttcggcgga cttcccgcca taacttctat taactcccag caccctgacg ccatcagggc

120

180

240

300

360

420

480

540

600

645 <210> 218 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 218

- 266 044746

Asp Ile Gln Met Thr 1 5

Gln Ser Pro Ser Ser

Leu Ser Ala Ser Val

Asp Arg Val Thr Ile

Thr Cys Gln Ala Ser

Gln Asp Ile Thr Asn 30

Leu Asn Trp Tyr Gln 35

Gln Lys Pro Gly Lys 40

Ala Pro Lys Leu Leu 45

Tyr Ala Ala Ser Asn 50

Leu Glu Thr Gly Val 55

Pro Ser Arg Phe Ser 60

Ser Gly Ser Gly Thr 65

Asp Phe Thr Phe Thr 70

Ile Ser Gly Leu Gln 75

Glu Asp Ile Ala Thr 85

Tyr Tyr Cys Gln Gln 90

Tyr Asp Asn Leu Pro 95

Thr Phe Gly Gly Gly

100

Thr Lys Val Glu Ile

105

Lys Arg Thr Val Ala

110

Pro Ser Val Phe Ile

115

Phe Pro Pro Ser Asp 120

Glu Gln Leu Lys Ser 125

Thr Ala Ser Val Val

130

Cys Leu Leu Asn Asn

135

Phe Tyr Pro Arg Glu 140

Lys Val Gln Trp Lys 145

Val Asp Asn Ala Leu 150

Gln Ser Gly Asn Ser 155

Glu Ser Val Thr Glu

165

Gln Asp Ser Lys Asp

170

Ser Thr Tyr Ser Leu

175

Ser Thr Leu Thr Leu

180

Ser Lys Ala Asp Tyr

185

Glu Lys His Lys Val

190

Ala Cys Glu Val Thr 195

His Gln Gly Leu Ser 200

Ser Pro Val Thr Lys

205

Gly

Tyr

Ile

Gly

Pro 80

Leu

Ala

Gly

Ala

Gln 160

Ser

Tyr

Ser

Phe Asn Arg Gly Glu 210

Cys <210> 219 <211> 360 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic

- 267 044746

<400> 219 gaggtgcagc tggtggagtc tgggggaggc ttggtaaagc ctggggggtc ccttagactc 60 tcctgtgcag cctctggaat cactttcagt aacgcctgga tgagttgggt ccgccaggct 120 ccagggaagg ggctggagtg ggttggccgt attaaaagca aaactgatgg tgggacaaca 180 gactacgccg cacccgtgaa aggcagattc accatctcaa gagatgattc aaaaaacacg 240 ctgtatctac aaatgaacag cctgaaaacc gaggacacag ccgtgtatta ctgtaccaca 300 gcgaggtggg actggtactt cgatctctgg ggccgtggca ccctggtcac tgtctcctca 360

<210> 220 <211> 120 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 220

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Lys Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Ile Thr Phe Ser Asn Ala 25 30

Trp Met Ser Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Gly Arg Ile Lys Ser Lys Thr Asp

55

Gly Gly Thr Thr Asp Tyr Ala Ala 60

Pro Val Lys Gly Arg Phe Thr Ile 65 70

Ser Arg Asp Asp Ser Lys Asn Thr

80

Leu Tyr Leu Gln Met Asn Ser Leu 85

Lys Thr Glu Asp Thr Ala Val Tyr

95

Tyr Cys Thr Thr Ala Arg Trp Asp

100

Trp Tyr Phe Asp Leu Trp Gly Arg

105 110

Gly Thr Leu Val Thr Val Ser Ser

115120 <210>221 <211>24 <212> DNA <213> Artificial sequence <220>

- 268 044746 <223> Synthetic <400>221 ggaatcactt tcagtaacgc ctgg <210>222 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>222

Gly Ile Thr Phe Ser Asn Ala Trp <210>223 <211>30 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>223 attaaaagca aaactgatgg tgggacaaca30 <210>224 <211>10 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>224

Ile Lys Ser Lys Thr Asp Gly Gly Thr Thr

510 < 210> 225 < 211> 33 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>225 accacagcga ggtgggactg gtacttcgat ctc <210>226 <211>11 <212> PROTEIN <213> Artificial sequence

- 269 044746 <220>

<223> Synthetic <400>226

Thr Thr Ala Arg Trp Asp Trp Tyr Phe Asp Leu

510 <210>227 <211>321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>227 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc60 atcacttgcc aggcgagtca ggacatttgg aattatataa attggtatca gcagaaacca120 gggaaggccc ctaagctcct gatctacgat gcatccaatt tgaaaa cagg ggtcccatca180 aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct240 gaagatattg caacatatta ctgtcaacag catgatgatc tccctccgac cttcggccaa300 gggaccaagg tggaaatcaa a321 <210>228 <21 1>107 < 212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>228

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Trp Asn Tyr 20 2530

Ile Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Asp Ala Ser Asn Leu Lys Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln His Asp Asp Leu Pro Pro 85 9095

- 270 044746

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100105 <210>229 <211>18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>229 caggacattt ggaattat <210>230 <211>6 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>230

Gln Asp Ile Trp Asn Tyr <210>231 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>231 caacagcatg atgatctccc tccgacc27 <210>232 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>232

Gln Gln His Asp Asp Leu Pro Pro Thr <210>233 <211>1353 <212> DNA <213> Artificial sequence

- 271 044746 <220>

<223> Synthetic

<400> 233 gaggtgcagc tggtggagtc tgggggaggc ttggtaaagc ctggggggtc ccttagactc 60 tcctgtgcag cctctggaat cactttcagt aacgcctgga tgagttgggt ccgccaggct 120 ccagggaagg ggctggagtg ggttggccgt attaaaagca aaactgatgg tgggacaaca 180 gactacgccg cacccgtgaa aggcagattc accatctcaa gagatgattc aaaaaacacg 240 ctgtatctac aaatgaacag cctgaaaacc gaggacacag ccgtgtatta ctgtaccaca 300 gcgaggtggg actggtactt cgatctctgg ggccgtggca ccctggtcac tgtctcctca 360 gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacacc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcggggaga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtacacc tgcccccatc ccgggatgag 1080 ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140 gccgtggagt ggggagagcaa tggggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1260 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320 cagaagtccc tctccctgtc tccggggtaaa tga 1353

<210> 234 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 234

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Lys Pro Gly Gly

5 10 15

- 272 044746

Ser

Trp

Gly

Pro 65

Leu

Tyr

Gly

Phe

Leu 145

Trp

Leu

Ser

Pro

Lys 225

Pro

Ser

Leu Arg Leu Ser Cys 20

Met Ser Trp Val Arg 35

Arg Ile Lys Ser Lys 50

Val Lys Gly Arg Phe 70

Tyr Leu Gln Met Asn 85

Cys Thr Thr Ala Arg 100

Thr Leu Val Thr Val

115

Pro Leu Ala Pro Ser 130

Gly Cys Leu Val Lys

150

Asn Ser Gly Ala Leu

165

Gln Ser Ser Gly Leu

180

Ser Ser Leu Gly Thr

195

Ser Asn Thr Lys Val 210

Thr His Thr Cys Pro

230

Ser Val Phe Leu Phe

245

Arg Thr Pro Glu Val

Ala Ala Ser Gly Ile 25

Gln Ala Pro Gly Lys 40

Thr Asp Gly Gly Thr 55

Thr Ile Ser Arg Asp

Ser Leu Lys Thr Glu 90

Trp Asp Trp Tyr Phe 105

Ser Ser Ala Ser Thr

120

Ser Lys Ser Thr Ser 135

Asp Tyr Phe Pro Glu

155

Thr Ser Gly Val His

170

Tyr Ser Leu Ser Ser 185

Gln Thr Tyr Ile Cys 200

Asp Lys Lys Val Glu 215

Pro Cys Pro Ala Pro

235

Pro Pro Lys Pro Lys

250

Thr Cys Val Val Val

Thr Phe Ser Asn Ala

Gly Leu Glu Trp Val 45

Thr Asp Tyr Ala Ala 60

Asp Ser Lys Asn Thr 80

Asp Thr Ala Val Tyr 95

Asp Leu Trp Gly Arg 110

Lys Gly Pro Ser Val

125

Gly Gly Thr Ala Ala 140

Pro Val Thr Val Ser

160

Thr Phe Pro Ala Val

175

Val Val Thr Val Pro

190

Asn Val Asn His Lys 205

Pro Lys Ser Cys Asp 220

Glu Leu Leu Gly Gly

240

Asp Thr Leu Met Ile

255

Asp Val Ser His Glu

- 273 044746

260

265

270

Asp Pro

Asn Ala

290

Val Val 305

Glu Tyr

Glu Val 275

Lys Thr

Ser Val

Lys Cys

Lys Phe

Asn Trp

280

Tyr Val

Asp Gly

Lys Thr

Ile Ser

340

Thr Leu

Pro Pro 355

Thr Cys

370

Leu Val

Lys Pro

Leu Thr 310

Lys Val 325

Lys Ala

Ser Arg

Lys Gly

Arg Glu 295

Val Leu

Ser Asn

Lys Gly

Asp Glu

360

Phe Tyr 375

Glu Gln

Tyr Asn

300

His Gln

Lys Ala

330

Glin Pro 345

Leu Thr

Pro Ser

Asp Trp 315

Leu Pro

Val Glu 285

Ser Thr

Leu Asn

Ala Pro

Val His

Tyr Arg

Gly Lys

320

Ile Glu

335

Arg Glu

Pro Gln

350

Val Tyr

Lys Asn

Gln Val 365

Ser Leu

Asp Ile

380

Ala Val

Glu Trp

Glu Ser 385

Asn Gly

Glin Pro

390

Glu Asn

Asn Tyr

Lys Thr 395

Thr Pro

Pro Val

400

Leu Asp

Ser Asp

Gly Ser 405

Phe Phe

Leu Tyr

410

Ser Lys

Leu Thr

Val Asp 415

Lys Ser

Arg Trp

420

Gln Gln

Gly Asn

Val Phe 425

Ser Cys

Ser Val

430

Met His

Glu Ala

Leu His 435

Asn His

Tyr Thr

440

Gln Lys

Ser Leu

Ser Leu 445

Ser Pro

Gly Lys

450 <210> 235 <211> 645 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 235 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc atcacttgcc aggcgagtca ggacatttgg aattatataa attggtatca gcagaaacca

120

- 274 044746 gggaaggccc aggttcagtg gaagatattg gggaccaagg tctgatgagc cccagagagg gagagtgtca ctgagcaaag ctgagctcgc ctaagctcct gaagtggatc caacatatta tggaaatcaa agttgaaatc ccaaagtaca cagagcagga cagactac ga ccgtcacaaa gatctacgat tgggacagat ctgtcaacag acgaactgtg tggaactgcc gtggaaggtg cagcaaggac gaaacacaaa gagcttcaac gcatccaatt tttactttca catgatgatc gctgcaccat tctgttgtgt gataacgccc agcacctaca gtctacgcct aggggaga gt tgaaaacagg ccatcagcag tccctccgac ctgtcttcat gcctgctgaa tccaatcggg gcctcagcag gcgaagtcac gttag ggtcccatca cctgcagcct cttcggccaa cttcccgcca taacttctat taactcccag caccctgacg ccatcagggc

180

240

300

360

420

480

540

600

645 <210> 236 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 236

Asp Ile 1

Gln Met

Thr Gln 5

Ser Pro

Ser Ser

Leu Ser

Ala Ser

Asp Arg

Val Thr

Ile Thr

Cys Gln

Ala Ser 25

Gln Asp

Ile Trp 30

Ile Asn

Trp Tyr 35

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

Lys Leu 45

Tyr Asp 50

Ala Ser

Asn Leu

Lys Thr 55

Gly Val

Pro Ser

Arg Phe

Ser Gly 65

Ser Gly

Thr Asp 70

Phe Thr

Phe Thr

Ile Ser 75

Ser Leu

Glu Asp

Ile Ala

Thr Tyr 85

Thr Phe

Gly Gln

100

Gly Thr

Pro Ser

Val Phe 115

Ile Phe

Thr Ala

Ser Val

Val Cys

Tyr Cys

Lys Val

Pro Pro

120

Leu Leu

Gln Gln

Glu Ile 105

Ser Asp

Asn Asn

His Asp

Lys Arg

Glu Gln

Phe Tyr

Asp Leu

Thr Val

110

Leu Lys 125

Pro Arg

Val Gly 15

Asn Tyr

Leu Ile

Ser Gly

Glin Pro 80

Pro Pro 95

Ala Ala

Ser Gly

Glu Ala

- 275 044746

130

135

140

Lys Val Gln Trp 145

Lys Val Asp Asn Ala Leu 150

Gln Ser Gly Asn Ser Gln

155 160

Glu Ser Val Thr

Glu Gln Asp Ser Lys Asp

165 170

Ser Thr Leu Thr

180

Leu Ser Lys Ala Asp Tyr

185

Ala Cys Glu Val

195

Thr His Gln Gly Leu Ser

200

Ser Thr Tyr Ser Leu Ser 175

Glu Lys His Lys Val Tyr 190

Ser Pro Val Thr Lys Ser 205

Phe Asn Arg Gly Glu Cys

210 <210>

<211>

<212>

<213>

237

360

DNA

Artificial sequence

Synthetic

237 <220>

<223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca ggggattact tggtggagtc cctctgggtt ggctggagtg agggccgatt gcctgagatc actacggtat tggaggaggc caccgtcagt ggtctcactt caccatctcc tgaggacacg ggacgtctgg ttggtccag c agcaactaca atttatagcg agacacaatt gccgtgtatt ggccaaggga ctggggggtc tgagctgggt gtggtagcac ccaagaacac actgtgcgag ccacggtcac cctgagactc ccgccaggct atactatgca gctgtatctt agtccccctg cgtctcctca

120

180

240

300

360 <210> 238 <211> 120 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>238

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser

2025

Gly Phe Thr Val Ser Ser Asn 30

- 276 044746

Tyr Met Ser Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Ser Leu Ile Tyr 50

Ser Gly Gly Ser 55

Thr Tyr Tyr Ala 60

Asp Ser Val Lys

Gly Arg Phe Thr 65

Ile Ser Arg His 70

Asn Ser Lys Asn 75

Thr Leu Tyr Leu 80

Gln Met Asn Ser

Leu Arg Ser Glu 85

Asp Thr Ala Val 90

Tyr Tyr Cys Ala 95

Arg Val Pro Leu

100

Gly Asp Tyr Tyr

Tyr Gly Met Asp 105

Val Trp Gly Gln

110

Gly Thr Thr Val Thr Val Ser Ser

115120 <210>239 <211>42 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>239 gcgagagtcc ccctggggga ttactactac ggtatggacg tc <210>240 <211>14 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>240

Ala Arg Val Pro Leu Gly Asp Tyr Tyr Tyr Gly Met Asp Val 1 510 <210>241 <211>321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 241 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc atcacttgcc aggcgagtca ggacattaac aagtatttaa attggtatca gcagaaacca

120

- 277 044746

gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaagatattg caacatatta ctgtcaacag tctgataatc tccctctcac tttcggcgga 300 gggaccaagg tggagatcaa a 321

<210> 242 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>242

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Asn Lys Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Ser Asp Asn Leu Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100105 <210>243 <211>18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>243 caggacatta acaagtat <210>244 <211>6 <212> PROTEIN <213> Artificial sequence

- 278 044746 <220>

<223> Synthetic <400>244

Gln Asp Ile Asn Lys Tyr < 210 > 245 < 211 > 27 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic <400>245 caacagtctg ataatctccc tctcact27 <210>246 <211>9 <212> PROTEIN <213>Artificial sequence <220>

< 223> Synthetic < 400>246

Gln Gln Ser Asp Asn Leu Pro Leu Thr 15 < 210 > 247 < 211 > 1353 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic <400>247 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc60 tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct120 ccagggaagg ggctggagtg ggtct cactt atttatagcg gtggtagcac atactatgca180 gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt240 caaatgaaca gcctgagatc tgaggacacg gccgtgtatt actgtgcgag agtccccctg300 ggggattact actacggtat ggacgtctgg ggcca aggga ccacggtcac cgtctcctca360 gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca540

- 279 044746 ggactctact tacatctgca aaatcttgtg ccgtcagtct gaggtcacat tacgtggacg agcacgtacc gagtacaagt aaagccaaag ctgaccaaga gccgtggagt ctggactccg cagcagggga cagaagtccc ccctcagcag acgtgaatca acaaaactca tcc tcttccc gcgtggtggt gcgtggaggt gtgtggtcag gcaaggtctc ggcagccccg accaggtcag gggagagcaa acggctcctt acgtcttctc tctccctgtc cgtggtgacc caagcccagc cacatgccca cccaaaaccc ggacgtgagc gcataatgcc cgtcctcacc caaca aagcc agaaccacag cctgacctgc tgggcagccg cttcctctac atgctccgtg tccgggtaaa gtgccctcca aacaccaagg ccgtgcccag aaggacaccc cacgaagacc aagacaaagc gtcctgcacc ctcccagccc gtgtacaccc ctggtcaaag gagaacaact agcaagctca atgcatgagg tga gcagcttggg tggacaagaa cacctgaact tcatgatctc ctgaggtcaa cgcgggagga aggactggct ccatcgagaa tgcccccatc gcttctatcc acaagaccac ccgt ggacaa ctctgcacaa cacccagacc agttgagccc cctgggggga ccggacccct gttcaactgg gcagtacaac gaatggcaag aaccatctcc ccgggatgag cagcgacatc gcctcccgtg gagcaggtgg ccactacacg

600

660

720

780

840

900

960

1020

1080

1140

1200

1260

1320

1353 <210> 248 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 248

Glu Val Gln Leu Val Glu Ser Gly 1 5

Ser Leu Arg Leu Ser Cys Ala Ala 20

Tyr Met Ser Trp Val Arg Gln Ala

40

Ser Leu Ile Tyr Ser Gly Gly Ser

55

Gly Arg Phe Thr Ile Ser Arg His 65 70

Gln Met Asn Ser Leu Arg Ser Glu 85

Gly

Ser 25

Pro

Thr

Asn

Asp

Gly Leu Val Gln Pro Gly Gly

15

Gly Phe Thr Val Ser Ser Asn 30

Gly Lys Gly Leu Glu Trp Val 45

Tyr Tyr Ala Asp Ser Val Lys 60

Ser Lys Asn Thr Leu Tyr Leu

80

Thr Ala Val Tyr Tyr Cys Ala 90 95

- 280 044746

Arg

Gly

Phe

Leu 145

Trp

Leu

Ser

Pro

Lys 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Val Pro

Thr Thr

115

Pro Leu 130

Gly Cys

Asn Ser

Gln Ser

Ser Ser

195

Ser Asn

210

Thr His

Ser Val

Arg Thr

Pro Glu

275

Ala Lys 290

Val Ser

Tyr Lys

Thr Ile

Leu Gly 100

Val Thr

Ala Pro

Leu Val

Asp Tyr

Val Ser

Ser Ser

135

Lys Asp 150

Gly Ala

165

Leu Thr

Tyr Tyr

105

Gly Met

Asp Val

Ser Ala 120

Ser Thr

Lys Gly

125

Lys Ser

Thr Ser

Gly Gly 140

Tyr Phe

Pro Glu

155

Pro Val

Trp Gly 110

Pro Ser

Thr Ala

Thr Val

Ser Gly

Val His 170

Thr Phe

Pro Ala

175

Ser Gly 180

Leu Gly

Thr Lys

Thr Cys

Phe Leu

245

Pro Glu 260

Val Lys

Thr Lys

Val Leu

Cys Lys

325

Ser Lys 340

Leu Tyr

Thr Gln

Val Asp

215

Pro Pro 230

Phe Pro

Val Thr

Phe Asn

Pro Arg

295

Thr Val 310

Val Ser

Ala Lys

Ser Leu

185

Ser Ser

Val Val

Thr Val 190

Thr Tyr 200

Ile Cys

Asn Val

205

Asn His

Lys Lys

Cys Pro

Pro Lys

Cys Val

265

Trp Tyr 280

Glu Glu

Leu His

Asn Lys

Gly Gln

345

Val Glu

Ala Pro

235

Pro Lys 250

Val Val

Val Asp

Gln Tyr

Gln Asp

315

Ala Leu 330

Pro Arg

Pro Lys 220

Glu Leu

Asp Thr

Asp Val

Gly Val

285

Asn Ser 300

Trp Leu

Pro Ala

Glu Pro

Ser Cys

Leu Gly

Leu Met

255

Ser His 270

Glu Val

Thr Tyr

Asn Gly

Pro Ile

335

Gln Val 350

Gln

Val

Ala

Ser 160

Val

Pro

Lys

Asp

Gly 240

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

- 281 044746

Thr

Leu

Pro

355

Pro

Ser

Arg

Asp

Glu

360

Leu

Thr

Lys

Asn

Gln

365

Val

Ser

Leu

Thr

Cys 370

Leu

Val

Lys

Gly

Phe

375

Tyr

Pro

Ser

Asp

Ile

380

Ala

Val

Glu

Trp

Glu

385

Ser

Asn

Gly

Gln

Pro

390

Glu

Asn

Asn

Tyr

Lys

395

Thr

Thr

Pro

Pro

Val

400

Leu

Asp

Ser

Asp

Gly 405

Ser

Phe

Phe

Leu

Tyr 410

Ser

Lys

Leu

Thr

Val

415

Asp

Lys

Ser

Arg

Trp 420

Gln

Gln

Gly

Asn

Val

425

Phe

Ser

Cys

Ser

Val

430

Met

His

Glu

Ala

Leu

435

His

Asn

His

Tyr

Thr

440

Gln

Lys

Ser

Leu

Ser

445

Leu

Ser

Pro

Gly Lys

450

<210> 249 <211> 645 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 249 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc aggcgagtca ggacattaac aagtatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaagatattg caacatatta ctgtcaacag tctgataatc tccctctcac tttcggcgga 300 gggaccaagg tggagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcaggggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 645

<210> 250 <211> 214

- 282 044746 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>250

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Asn Lys Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Ser Asp Asn Leu Pro Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105110

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

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210

- 283 044746 <210> 251 <211> 372 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 251

caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgtgcag cgtctggatt caccttcaga aactatggca tgcactgggt ccgccaggct 120 ccaggcaagg ggctggagtg ggtgtcagtt atatggtatg atggaagtaa tagatactat 180 gcagactccg tgaagggccg attcaccatc tccagagaca cttccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaagac acggctgtgt attackgtgc gagagatcct 300 cctataactg gaacgacggg gggcgatgct tttgatatct ggggccaagg gacaatggtc 360 accgtctctt ca 372

<210> 252 <211> 124 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 252

Gln Val Gln 1

Leu Val Glu Ser Gly Gly 5

Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg

Leu Ser Cys Ala Ala Ser

25

Gly Phe Thr Phe Arg Asn Tyr 30

Gly Met His

Trp Val Arg Gln Ala Pro

Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Trp 50

Tyr Asp Gly Ser Asn Arg 55

Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe 65

Thr Ile Ser Arg Asp Thr 70

Ser Lys Asn Thr Leu Tyr

80

Leu Gln Met Asn

Ser Leu Arg Ala Glu Asp 85 90

Thr Ala Val Tyr Tyr Cys 95

Ala Arg Asp Pro

100

Pro Ile Thr Gly Thr Thr

105

Gly Gly Asp Ala Phe Asp

110

- 284 044746

Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115

120 <210> 253 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>253 ggattcacct tcagaaacta tggc24 <210>254 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>254

Gly Phe Thr Phe Arg Asn Tyr Gly < 210>255 < 211>24 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>255 atatggtatg atggaagtaa taga24 <210>256 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>256

Ile Trp Tyr Asp Gly Ser Asn Arg <210>257 <211>51 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic

- 285 044746 <400>257 gcgagagatc ctcctataac tggaacgacg gggggcgatg cttttgatat c <210>258 <211>17 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>258

Ala Arg Asp Pro Pro Ile Thr Gly Thr Thr Gly Gly Asp Ala Phe Asp

5 1015

Ile < 210 > 259 < 211 > 321 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic <400>259 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc60 atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca120 gggaaagccc ctcacctcct gatctatgct gcatccagtt t gcaaagtgg ggtcccatca180 aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct240 gaagattttg caacttacta ctgtcaacag agttacagta ctccttacac ttttggccag300 gggaccaagc tggagatcaa a321 < 210>2 60 < 211>107 < 212> PROTEIN < 213> Artificial sequence < 220>

<223> Synthetic <400>260

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

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

- 286 044746

Leu Asn Trp 35 Tyr Gln Gln Lys Pro 40 Gly Lys Ala Pro His 45 Leu Leu Ile Tyr Ala 50 Ala Ser Ser Leu Gln 55 Ser Gly Val Pro Ser 60 Arg Phe Ser Gly Ser 65 Gly Ser Gly Thr Asp 70 Phe Thr Leu Thr Ile 75 Ser Ser Leu Gln Pro 80 Glu Asp Phe Ala Thr 85 Tyr Tyr Cys Gln Gln 90 Ser Tyr Ser Thr Pro 95 Tyr

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100105 <210>261 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>261 caacagagtt acagtactcc ttacact <210>262 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>262

Gln Gln Ser Tyr Ser Thr Pro Tyr Thr <210>263 <211>1365 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 263

caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgtgcag cgtctggatt caccttcaga aactatggca tgcactgggt ccgccaggct 120 ccaggcaagg ggctggagtg ggtgtcagtt atatggtatg atggaagtaa tagatactat 180 gcagactccg tgaagggccg attcaccatc tccagagaca cttccaagaa cacgctgtat 240

- 287 044746

ctgcaaatga acagcctgag agccgaagac acggctgtgt attackgtgc gagagatcct 300 cctataactg gaacgacggg gggcgatgct tttgatatct ggggccaagg gacaatggtc 360 accgtctctt cagcctccac caagggccca tcggtcttcc ccctggcacc ctcctccaag 420 agcacctctg ggggcacagc ggccctggggc tgcctggtca aggactactt ccccgaaccg 480 gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 540 ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 600 ggcaccaga cctacatctg caacgtgaat cacaagccca gcaacaccaa ggtggacag 660 aaagttgagc ccaaatcttg tgacaaaact cacacatgcc caccgtgccc agcacctgaa 720 ctcctgggggg gaccgtcagt cttcctcttc cccccaaaac ccaaggacac cctcatgatch 780 tcccggaccc ctgaggtcac atgcgtggtg gtggacgtga gccacgaaga ccctgaggtc 840 aagttcaact ggtacgtgga cggcgtggag gtgcataatg ccaagacaaa gccgcggggag 900 gagcagtaca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg 960 ctgaatggca aggagtacaa gtgcaaggtc tccaacaaag ccctcccagc ccccatcgag 1020 aaaaccatct ccaaagccaa agggcagccc cgagaaccac aggtgtacac cctgccccca 1080 tcccgggatg agctgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctat 1140 cccagcgaca tcgccgtgga gtgggagagc aatggggcagc cggagaacaa ctacaagacc 1200 acgcctcccg tgctggactc cgacggctcc ttcttcctct acagcaagct caccgtggac 1260 aagagcaggt ggcagcaggg gaacgtcttc tcatgctccg tgatgcatga ggctctgcac 1320 aaccactaca cgcagaagtc cctctccctg tctccggggta aatga 1365

<210> 264 <211> 454 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 264

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Arg Asn Tyr 25 30

Gly Met His Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Trp Tyr Asp Gly Ser

55

Asn Arg Tyr Tyr Ala Asp Ser Val 60

- 288 044746

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Thr 70

Ser Lys Asn Thr Leu 75

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Arg Asp Pro Pro

100

Ile Thr Gly Thr Thr

105

Gly Gly Asp Ala Phe

110

Ile Trp Gly Gln Gly 115

Thr Met Val Thr Val

120

Ser Ser Ala Ser Thr

125

Gly Pro Ser Val Phe 130

Pro Leu Ala Pro Ser

135

Ser Lys Ser Thr Ser 140

Gly Thr Ala Ala Leu 145

Gly Cys Leu Val Lys 150

Asp Tyr Phe Pro Glu 155

Val Thr Val Ser Trp

165

Asn Ser Gly Ala Leu

170

Thr Ser Gly Val His

175

Phe Pro Ala Val Leu

180

Gln Ser Ser Gly Leu

185

Tyr Ser Leu Ser Ser

190

Val Thr Val Pro Ser

195

Ser Ser Leu Gly Thr

200

Gln Thr Tyr Ile Cys

205

Val Asn His Lys Pro

210

Ser Asn Thr Lys Val

215

Asp Lys Lys Val Glu

220

Lys Ser Cys Asp Lys 225

Thr His Thr Cys Pro 230

Pro Cys Pro Ala Pro 235

Leu Leu Gly Gly Pro

245

Ser Val Phe Leu Phe

250

Pro Pro Lys Pro Lys

255

Thr Leu Met Ile Ser

260

Arg Thr Pro Glu Val

265

Thr Cys Val Val Val

270

Val Ser His Glu Asp

275

Pro Glu Val Lys Phe

280

Asn Trp Tyr Val Asp

285

Val Glu Val His Asn

290

Ala Lys Thr Lys Pro

295

Arg Glu Glu Gln Tyr 300

Ser Thr Tyr Arg Val

Val Ser Val Leu Thr

Val Leu His Gln Asp

Tyr 80

Cys

Asp

Lys

Gly

Pro 160

Thr

Val

Asn

Pro

Glu 240

Asp

Asp

Gly

Asn

Trp

- 289 044746

305

310

315

320

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

325 330335

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

340 345350

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

355 360365

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

370 375380

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

385 390 395400

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

405 410415

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

420 425430

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

435 440445

Ser Leu Ser Pro Gly Lys

450 <210>

<211>

<212>

<213>

265

645

DNA

Artificial sequence

Synthetic

265 <220>

<223>

<400>

gacatccaga atcacttgcc gggaaagccc aggttcagtg gaagattttg gggaccaagc tctgatgagc cccagagagg tgacccagtc gggcaagtca ctcacctcct gcagtggatc caacttacta tggagatcaa agttgaaatc ccaaagtaca tccatcctcc gagcattagc gatctatgct tgg gacagat ctgtcaacag acgaactgtg tggaactgcc gtggaaggtg ctgtctgcat agctatttaa gcatccagtt ttcactctca agttacagta gctgcaccat tctgttgtgt gataacgccc ctgtaggaga attggtatca tgcaaagtgg ccatcagcag ctccttacac ctgtcttcat gcctgctgaa tccaatcggg cagagtcacc gcagaaacca ggtcccatca tctgcaacct ttttggccag cttcccgcca taacttctat taactcccag

120

180

240

300

360

420

480

- 290 044746 caccctgacg ccatcagggc gagagtgtca ctgagcaaag ctgagctcgc cagagcagga cagactacga ccgtcacaaa cagcaaggac gaaacacaaa gagcttcaac agcacctaca gtctacgcct aggggagagt gcctcagcag gcgaagtcac gttag

540

600

645 <210> 266 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 266

Asp Ile 1

Gln Met

Thr Gln 5

Ser Pro

Ser Ser

Leu Ser

Ala Ser

Asp Arg

Val Thr

Ile Thr

CysArg

Ala Ser 25

Gln Ser

Ile Ser

Leu Asn

Trp Tyr 35

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

His Leu 45

Tyr Ala 50

Ala Ser

Ser Leu

Gln Ser 55

Gly Val

Pro Ser

Arg Phe

Val Gly 15

Ser Tyr

Leu Ile

Ser Gly

Ser Gly 65

Ser Gly

Thr Asp 70

Phe Thr

Leu Thr

Ile Ser 75

Ser Leu

Glin Pro

Glu Asp

Phe Ala

Thr Tyr 85

Tyr Cys

Gln Gln

Ser Tyr

Ser Thr

Pro Tyr 95

Thr Phe

Gly Gln

100

Gly Thr

Lys Leu

Glu Ile 105

Lys Arg

Thr Val

110

Ala Ala

Pro Ser

Val Phe 115

Ile Phe

Pro Pro

120

Ser Asp

Glu Gln

Leu Lys 125

Ser Gly

Thr Ala

130

Ser Val

Val Cys

Leu Leu 135

Lys Val 145

Gln Trp

Lys Val

150

Asp Asn

Glu Ser

Val Thr

Glu Gln 165

Asp Ser

Ser Thr

Leu Thr

Leu Ser

Lys Ala

Asn Asn

Ala Leu

Lys Asp

170

Asp Tyr

Phe Tyr

140

Pro Arg

Glu Ala

Gln Ser 155

Gly Asn

Ser Gln

160

Ser Thr

Tyr Ser

Leu Ser 175

Glu Lys

His Lys

Val Tyr

- 291 044746

180

185

190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210 <210>267 <211>357 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 267 cagatcacct tgaaggagtc tggtcctacg ctggtgaaac ccacacagac cctcacgctg acctgcacct tctctgggtt ctcactcagc actaatgtag tgggtgtggg ctggatccgt cagcccccag gaaaggccct ggagtggctt gcactcat tt attggaatga tgataagcgc tacagcccat ctctgaagag caggctcacc atcaccaagg acacctccaa aaaccaggtg gtccttacaa tgaccaacat ggaccctgtg gacacagcca catattactg tgcacacggc ccaactgggg actactttga ctactggggc cagggaaccc tggtcaccgt ctcctca

120

180

240

300

357 <210> 268 <211> 119 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>268

Gln Ile Thr Leu Lys Glu Ser Gly Pro Thr Leu Val Lys Pro Thr Gln

5 1015

Thr Leu Thr Leu Thr Cys Thr Phe Ser Gly Phe Ser Leu Ser Thr Asn 20 2530

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

4045

Trp Leu Ala Leu Ile Tyr Trp Asn Asp Asp Lys Arg Tyr Ser Pro Ser 50 5560

Leu Lys Ser Arg Leu Thr Ile Thr Lys Asp Thr Ser Lys Asn Gln Val 65 70 7580

- 292 044746

Val Leu Thr Met

Thr Asn Met Asp Pro Val Asp Thr Ala Thr Tyr Tyr 85 90 95

Cys Ala His

Gly Pro Thr Gly Asp Tyr Phe Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser

115 <210> 269 <211> 30 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 269 gggttctcac tcagcactaa tgtagtgggt <210> 270 <211> 10 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 270

Gly Phe Ser Leu Ser Thr Asn Val Val Gly

5 10 <210> 271 <211> 21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 271 atttattgga atgatgataa g <210> 272 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 272

Ile Tyr Trp Asn Asp Asp Lys

5

- 293 044746 <210> 273 <211> 33 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>273 gcacacggcc caactgggga ctactttgac tac <210>274 <211>11 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>274

Ala His Gly Pro Thr Gly Asp Tyr Phe Asp Tyr

510 <210>275 <211>324 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 275 gacatccaga atcacttgcc gggaaagccc aggttcagtg gaagattttg caggggacca tgacccagtc gggcaagtca ctaagctcct gcagtggatc caacttacta agctggagat tccatcctcc gagcattagc gatctatgct tgggacagat ctgtcaacag caaa ctgtctgcat agctatttaa gcatccagtt ttcactctca acttacagta ctgtaggaga attggtatca tacaaagtgg ccatcagcag ccctcatgta cagagtcacc gcagaaacca ggtcccatca tctgcaacct cacttttggc

120

180

240

300

324 <210> 276 <211> 108 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 276

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

- 294 044746

Asp Arg Val Thr Ile Thr Cys Arg 20

Ala Ser Gln Ser Ile Ser Ser Tyr 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro

40

Gly Lys Ala Pro Lys Leu Leu Ile 45

Tyr Ala Ala Ser Ser Leu Gln Ser

55

Gly Val Pro Ser Arg Phe Ser Gly 60

Ser Gly Ser Gly Thr Asp Phe Thr 65 70

Leu Thr Ile Ser Ser Leu Gln Pro

80

Glu Asp Phe Ala Thr Tyr Tyr Cys 85

Gln Gln Thr Tyr Ser Thr Leu Met

95

Tyr Thr Phe Gly Gln Gly Thr Lys

100

Leu Glu Ile Lys 105 <210> 277 <211> 30 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 277 caacagactt acagtaccct catgtacact <210> 278 <211> 10 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 278

Gln Gln Thr Tyr Ser Thr Leu Met Tyr Thr

5 10 <210> 279 <211> 1350 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 279 cagatcacct tgaaggagtc tggtcctacg ctggtgaaac ccacacagac cctcacgctg acctgcacct tctctgggtt ctcactcagc actaatgtag tgggtgtggg ctggatccgt

120

- 295 044746

cagcccccag gaaaggccct ggagtggctt gcactcattt attggaatga tgataagcgc 180 tacagcccat ctctgaagag caggctcacc atcaccaagg acacctccaa aaaccaggtg 240 gtccttacaa tgaccaacat ggaccctgtg gacacagcca catattactg tgcacacggc 300 ccaactgggg actactttga ctactggggc cagggaaccc tggtcaccgt ctcctcagcc 360 tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctggggggc 420 acaggccc tggggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac ccagacctac 600 atctgcaacg tgaatcacaa gccagcaac accaaggtgg acaagaaagt tgagcccaaa 660 tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720 tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780 gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840 gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900 acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaagggag 960 tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020 gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080 accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140 gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200 gactccgacg gctccttctt ccctacagc aagctcaccg tggacaagag caggtggcag 1260 caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320 aagtccctct ccctgtctcc gggtaaatga 1350

<210> 280 <211> 449 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 280

Gln 1

Ile

Thr

Leu

Lys 5

Glu

Ser

Gly

Pro

Thr 10

Leu

Val

Lys

Pro

Thr 15

Gln

Thr

Leu

Thr

Leu 20

Thr

Cys

Thr

Phe

Ser 25

Gly

Phe

Ser

Leu

Ser 30

Thr

Asn

Val

Val

Gly 35

Val

Gly

Trp

Ile

Arg 40

Gln

Pro

Pro

Gly

Lys 45

Ala

Leu

Glu

- 296 044746

Trp

Leu 65

Val

Cys

Thr

Pro

Gly 145

Asn

Gln

Ser

Ser

Thr 225

Ser

Arg

Pro

Ala

Leu Ala Leu Ile Tyr 50

Lys Ser Arg Leu Thr 70

Leu Thr Met Thr Asn

Ala His Gly Pro Thr 100

Leu Val Thr Val Ser

115

Leu Ala Pro Ser Ser 130

Cys Leu Val Lys Asp

150

Ser Gly Ala Leu Thr

165

Ser Ser Gly Leu Tyr

180

Ser Leu Gly Thr Gln

195

Asn Thr Lys Val Asp 210

His Thr Cys Pro Pro

230

Val Phe Leu Phe Pro

245

Thr Pro Glu Val Thr

260

Glu Val Lys Phe Asn

275

Lys Thr Lys Pro Arg

Trp Asn Asp Asp Lys 55

Ile Thr Lys Asp Thr

Met Asp Pro Val Asp

Gly Asp Tyr Phe Asp

105

Ser Ala Ser Thr Lys 120

Lys Ser Thr Ser Gly 135

Tyr Phe Pro Glu Pro

155

Ser Gly Val His Thr

170

Ser Leu Ser Ser Val

185

Thr Tyr Ile Cys Asn

200

Lys Lys Val Glu Pro 215

Cys Pro Ala Pro Glu

235

Pro Lys Pro Lys Asp

250

Cys Val Val Val Asp

265

Trp Tyr Val Asp Gly

280

Glu Glu Gln Tyr Asn

Arg Tyr Ser Pro Ser 60

Ser Lys Asn Gln Val 80

Thr Ala Thr Tyr Tyr 95

Tyr Trp Gly Gln Gly 110

Gly Pro Ser Val Phe

125

Gly Thr Ala Ala Leu 140

Val Thr Val Ser Trp

160

Phe Pro Ala Val Leu

175

Val Thr Val Pro Ser

190

Val Asn His Lys Pro

205

Lys Ser Cys Asp Lys 220

Leu Leu Gly Gly Pro

240

Thr Leu Met Ile Ser

255

Val Ser His Glu Asp

270

Val Glu Val His Asn

285

Ser Thr Tyr Arg Val

- 297 044746

290

295

300

Val Ser 305

Tyr Lys

Thr Ile

Leu Pro

Cys Leu 370

Ser Asn 385

Asp Ser

Ser Arg

Ala Leu

Val Leu

Thr Val

310

Leu His

Gln Asp

Lys

Cys Lys

Ser Lys

340

Pro Ser 355

Val Lys

Gly Gln

Asp Gly

Trp Gln

420

His Asn 435

Val Ser 325

Asn Lys

Ala Leu

330

Ala Lys

Arg Asp

Gly Phe

Pro Glu

390

Ser Phe

405

Gln Gly

His Tyr

281

648

DNA

Artificial

Synthetic

281 <210>

<211>

<212>

<213>

<220>

<223>

<400>

gacatccaga atcacttgcc gggaaagccc aggttcagtg gaagattttg caggggacca

Gly Gln

Glu Leu

360

Tyr Pro 375

Asn Asn

Phe Leu

Asn Val

Thr Gln

440

Pro Arg 345

Thr Lys

Ser Asp

Tyr Lys

Tyr Ser

410

Phe Ser 425

Lys Ser

Trp Leu 315

Pro Ala

Glu Pro

Asn Gln

Ile Ala

380

Thr Thr 395

Lys Leu

Cys Ser

Leu Ser

Asn Gly

Pro Ile

Gln Val

350

Val Ser 365

Val Glu

Pro Pro

Thr Val

Val Met

430

Leu Ser 445 sequence tgacccagtc gggcaagtca ctaagctcct gcagtggatc caacttacta agctggagat tccatcctcc gagcattagc gatctatgct tgggacagat ctgtcaacag caaacgaact ctgtctgcat agctatttaa gcatccagtt ttcactctca acttacagta gtggctgcac ctgta ggaga attggtatca tacaaagtgg ccatcagcag ccctcatgta catctgtctt

Lys Glu

320

Glu Lys 335

Tyr Thr

Leu Thr

Trp Glu

Val Leu

400

Asp Lys 415

His Glu

Pro Gly cagagtcacc gcagaaacca ggtcccatca tctgcaacct cacttttggc catcttcccg

120

180

240

300

360

- 298 044746 ccatctgatg tatcccagag caggagagtg acgctgagca ggcctgagct agcagttgaa aggccaaagt tcacagagca aagcagacta cgcccgtcac atctggaact acagtggaag ggacagcaag cgagaaacac aaagagcttc gcctctgttg gtggataacg g acagcacct aaagtctacg aacaggggag tgtgcctgct ccctccaatc acagcctcag cctgcgaagt agtgttag gaataacttc gggtaactcc cagcaccctg cacccatcag

420

480

540

600

648 <210> 282 <211> 215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 282

Asp Ile 1

Gln Met

Thr Gln 5

Ser Pro

Ser Ser

Leu Ser

Ala Ser

Asp Arg

Val Thr

Ile Thr

CysArg

Ala Ser 25

Gln Ser

Ile Ser

Leu Asn

Trp Tyr 35

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

Lys Leu 45

Tyr Ala 50

Ala Ser

Ser Leu

Gln Ser 55

Gly Val

Pro Ser

Arg Phe

Ser Gly 65

Ser Gly

Thr Asp 70

Phe Thr

Leu Thr

Ile Ser 75

Ser Leu

Glu Asp

Phe Ala

Thr Tyr 85

Tyr Cys

Gln Gln

Thr Tyr

Ser Thr

Tyr Thr

Phe Gly

100

Gln Gly

Thr Lys

Leu Glu 105

Ile Lys

Arg Thr

110

Ala Pro

Ser Val 115

Gly Thr

130

Ala Ser

Ala Lys 145

Val Gln

Gln Glu

Ser Val

Phe Ile

Val Val

Trp Lys

150

Thr Glu

Phe Pro

120

Pro Ser

Asp Glu

Gln Leu 125

Cys Leu 135

Leu Asn

Asn Phe

140

Tyr Pro

Val Asp

Asn Ala

Leu Gln 155

Ser Gly

Gln Asp

Ser Lys

Asp Ser

Thr Tyr

Val Gly 15

Ser Tyr

Leu Ile

Ser Gly

Glin Pro 80

Leu Met 95

Val Ala

Lys Ser

Arg Glu

Asn Ser

160

Ser Leu

- 299 044746

165 170 175 Ser Ser Thr Leu 180 Thr Leu Ser Lys Ala 185 Asp Tyr Glu Lys His 190 Lys Val Tyr Ala Cys 195 Glu Val Thr His Gln 200 Gly Leu Ser Ser Pro 205 Val Thr Lys Ser Phe 210 Asn Arg Gly Glu Cys 215

<210>

<211>

<212>

<213>

283

366

DNA

Artificial sequence

Synthetic

283 <220> <223>

<400>

gaagtgcagc tcctgtgcag ccagggaagg gcggactctg ctgcaaatga gggaggctag tggtggagtc cctctggatt gcctggagtg tgaagggccg acagtctgag actactactc tgggggaggc cacctttgat ggtctcaggt attcaccatt agctgaagac cggtttggac ttggttcagc gattatgcca gttagttgga attagagaca acggccttgt gtctggggcc ctggcaggtc tgcactgggt atagtggtac acgctaagaa attactgttc aagggaccac cctgagactc ccggcaagct catagactat ctccctgtat aaaagatatg ggtcaccgtc tcctca

120

180

240

300

360

366 <210> 284 <211> 122 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 284

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Asp Asp Tyr 25 30

Ala Met His Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Gly Val Ser Trp Asn Ser Gly

55

Thr Ile Asp Tyr Ala Asp Ser Val 60

- 300 044746

Lys Gly Arg Phe Thr Ile Ile Arg 65 70

Asp Asn Ala Lys Asn Ser Leu Tyr

80

Leu Gln Met Asn Ser Leu Arg Ala 85

Glu Asp Thr Ala Leu Tyr Tyr Cys

95

Ser Lys Asp Met Gly Arg Leu Asp

100

Tyr Tyr Ser Gly Leu Asp Val Trp

105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115120 <210>285 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>285 gttagttgga atagtggtac cata <210>286 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>286

Val Ser Trp Asn Ser Gly Thr Ile <210>287 <211>45 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>287 tcaaaagata tggggaggct agactactac tccggtttgg acgtc <210>288 <211>15 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic

- 301 044746 <400>288

Ser Lys Asp Met Gly Arg Leu Asp Tyr Tyr Ser Gly Leu Asp Val 1 5 1015 <210>289 <211>324 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>289 gaaatagtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc60 ctctcctgca gggccagtca gagtgttagc agcagcgact ttgcctggta ccagcagaaa120 cctggccagg ctcccaggct cctcatctat gg tgcatcca gcagggccac tggtatccca180 gacaggttca gtggcagtgg gtctgggaca gatttcactc tcaccatcag cagactggag240 cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccttg gacgttcggc300 caagggacca aggtggaaat caaa324 <2 10>290 <211>108 < 212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 290

Glu Ile Val Leu Thr Gln Ser Pro 1 5

Gly Thr Leu Ser Leu Ser 10

Glu Arg Ala Thr Leu Ser Cys Arg 20

Ala Ser Gln Ser Val Ser

thirty

Asp Phe Ala Trp Tyr Gln Gln Lys

40

Ile Tyr Gly Ala Ser Ser Arg Ala

55

Gly Ser Gly Ser Gly Thr Asp Phe 65 70

Pro Glu Asp Phe Ala Val Tyr Tyr 85

Pro Gly Gln Ala Pro Arg 45

Thr Gly Ile Pro Asp Arg 60

Thr Leu Thr Ile Ser Arg 75

Cys Gln Gln Tyr Gly Ser 90

Pro Gly 15

Ser Ser

Leu Leu

Phe Ser

Leu Glu 80

Ser Pro 95

- 302 044746

Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100

105 <210> 291 <211> 21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>291 cagagtgtta gcagcagcga c21 <210>292 <211>7 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>292

Gln Ser Val Ser Ser Ser Asp <210>293 <211>9 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 293 ggtgcatcc

<210> 294 <211> 3 <212> PROTEIN <213> Artificial sequence <220> <223> Synthetic <400> 294 Gly Ala 1 Ser

<210> 295 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

- 303 044746 <400>295 cagcagtatg gtagctcacc ttggacg <210>296 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>296

Gln Gln Tyr Gly Ser Ser Pro Trp Thr 15 < 210 > 297 < 211 > 1359 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic

<400> 297 gaagtgcagc tggtggagtc tgggggaggc ttggttcagc ctggcaggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120 ccagggaagg gcctggagtg ggtctcaggt gttagttgga atagtggtac catagactat 180 gcggactctg tgaagggccg attcaccatt attagagaca acgctaagaa ctccctgtat 240 ctgcaaatga acagtctgag agctgaagac acggccttgt attackgttc aaaagatatg 300 gggaggctag actactactc cggtttggac gtctggggcc aagggaccac ggtcaccgtc 360 tcctcagcct ccaccaaggg cccacggtc ttccccctgg caccctcctc caagagcacc 420 tctggggggca cagcggccct gggctgcctg gtcaaggact acttccccga accggtgacg 480 gtgtcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 540 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttggggcacc 600 cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagaaagtt 660 gagcccaaat cttgtgacaa aactcacaca tgccaccgt gccagcacc tgaactcctg 720 gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 780 acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 840 aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggagaggagcag 900 tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 960 ggcaagggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1020 atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccacccgg 1080

- 304 044746 gatgagctga gacatcgccg cccgtgctgg aggtggcagc tacacgcaga ccaagaacca tggagtggga actccgacgg aggggaacgt agtccctctc ggtcagcctg gagcaatggg ctccttcttc cttctcatgc cctgtctccg acctgcctgg cagccgg aga ctctacagca tccgtgatgc ggtaaatga tcaaaggctt acaactacaa agctcaccgt atgaggctct ctatcccagc gaccacgcct ggacaagagc gcacaaccac

1140

1200

1260

1320

1359 <210> 298 <211> 452 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 298

Glu Val 1

Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg

10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

25

Thr Phe Asp Asp Tyr 30

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys

40

Gly Leu Glu Trp Val 45

Ser Gly Val Ser Trp Asn Ser Gly Thr Ile Asp

55

Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ile Arg Asp Asn Ala 65 70 75

Lys Asn Ser Leu Tyr 80

Leu Gln Met Asn

Ser Leu Arg Ala 85

Glu Asp Thr Ala Leu Tyr Tyr Cys

95

Ser Lys Asp Met

100

Gly Arg Leu Asp Tyr Tyr Ser Gly Leu Asp Val Trp

105 110

Gly Gln

Ser Val

130

Ala Ala 145

Val Ser

Gly Thr 115

Phe Pro

Leu Gly

Trp Asn

Thr Val

Leu Ala

Cys Leu

150

Ser Gly

Thr Val

120

Ser Ser

Ala Ser

Pro Ser 135

Ser Lys

Ser Thr

140

Val Lys

Asp Tyr

Phe Pro 155

Ala Leu

Thr Ser

Gly Val

Thr Lys 125

Ser Gly

Glu Pro

His Thr

Gly Pro

Gly Thr

Val Thr

160

Phe Pro

- 305 044746

165

170

175

Ala

Val

His

Cys 225

Gly

Met

His

Val

Tyr 305

Gly

Ile

Val

Ser

Glu 385

Pro

Val Leu Gln

180

Pro Ser Ser

195

Lys Pro Ser 210

Asp Lys Thr

Gly Pro Ser

Ile Ser Arg

260

Glu Asp Pro

275

His Asn Ala 290

Arg Val Val

Lys Glu Tyr

Glu Lys Thr

340

Tyr Thr Leu

355

Leu Thr Cys 370

Trp Glu Ser

Val Leu Asp

Ser Ser Gly

Ser Leu Gly

Asn Thr Lys

215

His Thr Cys

230

Val Phe Leu 245

Thr Pro Glu

Glu Val Lys

Lys Thr Lys

295

Ser Val Leu

310

Lys Cys Lys 325

Ile Ser Lys

Pro Pro Ser

Leu Val Lys

375

Asn Gly Gln

390

Ser Asp Gly 405

Leu Tyr Ser

185

Thr Gln Thr 200

Val Asp Lys

Pro Pro Cys

Phe Pro Pro

250

Val Thr Cys

265

Phe Asn Trp 280

Pro Arg Glu

Thr Val Leu

Val Ser Asn

330

Ala Lys Gly 345

Arg Asp Glu 360

Gly Phe Tyr

Pro Glu Asn

Ser Phe Phe

410

Leu Ser Ser

Tyr Ile Cys

205

Lys Val Glu

220

Pro Ala Pro 235

Lys Pro Lys

Val Val Val

Tyr Val Asp

285

Glu Gln Tyr

300

His Gln Asp 315

Lys Ala Leu

Gln Pro Arg

Leu Thr Lys

365

Pro Ser Asp

380

Asn Tyr Lys 395

Leu Tyr Ser

Val Val Thr 190

Asn Val Asn

Pro Lys Ser

Glu Leu Leu

240

Asp Thr Leu

255

Asp Val Ser 270

Gly Val Glu

Asn Ser Thr

Trp Leu Asn

320

Pro Ala Pro

335

Glu Pro Gln 350

Asn Gln Val

Ile Ala Val

Thr Thr Pro

400

Lys Leu Thr

415

- 306 044746

Val Asp Lys Ser Arg Trp Gln Gln 420

Gly Asn Val Phe Ser Cys Ser Val

425 430

Met His

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

435 440 445

Ser Pro Gly Lys

450

<210> 299 <211> 648 <212> DNA <213> Artificial subsequence <220> <223> Synthetic <400> 299 gaaatagtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 ctctcctgca gggccagtca gagtgttagc agcagcgact ttgcctggta ccagcagaaa 120 cctggccagg ctcccaggct cctcatcatat ggtgcatcca gcaggggccac tggtatccca 180 gacaggttca gtggcagtgg gtctgggaca gatttcactc tcaccatcag cagactggag 240 cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccttg gacgttcggc 300 caagggacca aggtggaaat caaacgaact gtggctgcac catctgtctt catcttcccg 360 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420 tatccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 648

<210> 300 <211> 215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>300

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

5 1015

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser 20 2530

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

- 307 044746

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 5560

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 7580

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro 85 9095

Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala

100 105110

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

115 120125

Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu

130 135140

Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser

145 150 155160

Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu

165 170175

Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val

180 185190

Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys

195 200205

Ser Phe Asn Arg Gly Glu Cys

210215 <210>

<211>

<212>

<213>

301

354

DNA

Artificial sequence

Synthetic

301 <220>

<223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg gactccgtga tggtggagtc tctctgggtt gactggaatg agggccgatt tggaggaggc caccgtcagt ggtctcactt caccatctcc ttggtccagc agcaactaca atttatagcg agacacaatt ctggggggtc tgagctgggt gtggtagca c ccaagaacac cctgagactc ccgccaggct attctacgca gctgtatctt

120

180

240

- 308 044746 caaatgaaca gcctgagagc tgaggacacg gccgtatatt actgtgcgag agaaggtgga

300 tacagctatg attacaacta ctggggccag ggaaccctgg tcaccgtctc ctca 354 <210> 302 <211> 118 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 302

Glu Val Gln Leu Val Glu Ser Gly Gly 1 5

Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Val Ser 20 25

Tyr Met Ser Trp Val Arg Gln Ala Pro 35 40

Gly Phe Thr Val Ser Ser Asn 30

Gly Lys Gly Leu Glu Trp Val 45

Ser Leu Ile Tyr 50

Gly Arg Phe Thr 65

Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 55 60

Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu 70 75 80

Gln Met Asn

Ser Leu Arg Ala Glu Asp Thr Ala Val

90

Arg Glu Gly

Gly Tyr Ser Tyr Asp Tyr Asn Tyr Trp 100 105

Tyr Tyr Cys Ala 95

Gly Gln Gly Thr 110

Leu Val Thr Val Ser Ser

115 <210> 303 <211> 36 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>303 gcgagagaag gtggatacag ctatgattac aactac <210>304 <211>12 <212> PROTEIN

- 309 044746 <213> Artificial sequence <220>

<223> Synthetic <400>304

Ala Arg Glu Gly Gly Tyr Ser Tyr Asp Tyr Asn Tyr 1 510 <210>305 <211>321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 305

gacatccaga tgaccagtc tccatcctcc ctgtccgcat ctgtaggaga cagagtcacc 60 atcacgtgcc aggcgagtca ggacattaga aactatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaattggatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaagatattg caacatatta ctgtcaacag tatgataacc tccctatcac cttcggccaa 300 gggacacgac tggagattaa a 321

<210> 306 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>306

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Arg Asn Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ile Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 65 70 7580

- 310 044746

Glu Asp Ile Ala Thr Tyr Tyr Cys 85

Gln Gln Tyr Asp Asn Leu Pro Ile

Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys

100105 <210>307 <211>18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>307 caggacatta gaaactat <210>308 <211>6 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>308

Gln Asp Ile Arg Asn Tyr <210>309 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>309 caacagtatg ataacctccc tatcacc <210>310 <211>9 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>310

Gln Gln Tyr Asp Asn Leu Pro Ile Thr <210> 311 <211> 1347 <212> DNA

- 311 044746 <213> Artificial sequence <220>

<223> Synthetic <400>311 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc60 tcctgtgcag tctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct120 ccagggaagg gactggaatg ggtctcactt atttatagcg gtggtagcac attctacgca180 gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt240 caaatgaaca gcctgagagc tgaggacacg gccgtatatt actgtgcgag agaaggtgga300 tacagctatg attacaacta ctggggccag ggaaccctgg t caccgtctc ctcagcctcc360 accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tgggggcaca420 gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac480 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc540 tactccctca gcagcgtggt gaccgtgccc tccagcagct tgggcaccca gacctacatc 600 tgcaacgtga atcacaagcc cagcaacacc aaggtggaca agaaagttga gcccaaatct660 tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctggg gggaccgtca720 gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc7 80 acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg840 gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg900 taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac960 aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc1020 aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc1080 aagaaccagg tcagcctgac ctg cctggtc aaaggcttct atcccagcga catcgccgtg1140 gagtgggaga gcaatgggca gccggagaac aactacaaga ccacgcctcc cgtgctggac1200 tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag1260 gggaacgtct tctcatg ctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag1320 tccctctccc tgtctccggg taaatga1347 <210>312 <211> 448 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 312

- 312 044746

Glu 1

Ser

Tyr

Ser

Gly 65

Gln

Arg

Leu

Leu

Cys 145

Ser

Ser

Ser

Asn

His 225

Val

Val Gln Leu Val Glu

Leu Arg Leu Ser Cys 20

Met Ser Trp Val Arg 35

Leu Ile Tyr Ser Gly 50

Arg Phe Thr Ile Ser 70

Met Asn Ser Leu Arg 85

Glu Gly Gly Tyr Ser

100

Val Thr Val Ser Ser

115

Ala Pro Ser Ser Lys 130

Leu Val Lys Asp Tyr

150

Gly Ala Leu Thr Ser

165

Ser Gly Leu Tyr Ser

180

Leu Gly Thr Gln Thr

195

Thr Lys Val Asp Lys 210

Thr Cys Pro Pro Cys

230

Phe Leu Phe Pro Pro

245

Ser Gly Gly Gly Leu

Ala Val Ser Gly Phe 25

Gln Ala Pro Gly Lys 40

Gly Ser Thr Phe Tyr 55

Arg His Asn Ser Lys 75

Ala Glu Asp Thr Ala 90

Tyr Asp Tyr Asn Tyr 105

Ala Ser Thr Lys Gly 120

Ser Thr Ser Gly Gly 135

Phe Pro Glu Pro Val

155

Gly Val His Thr Phe

170

Leu Ser Ser Val Val

185

Tyr Ile Cys Asn Val

200

Lys Val Glu Pro Lys 215

Pro Ala Pro Glu Leu

235

Lys Pro Lys Asp Thr

250

Val Gln Pro Gly Gly

Thr Val Ser Ser Asn

Gly Leu Glu Trp Val 45

Ala Asp Ser Val Lys 60

Asn Thr Leu Tyr Leu 80

Val Tyr Tyr Cys Ala

Trp Gly Gln Gly Thr

110

Pro Ser Val Phe Pro

125

Thr Ala Ala Leu Gly 140

Thr Val Ser Trp Asn

160

Pro Ala Val Leu Gln

175

Thr Val Pro Ser Ser

190

Asn His Lys Pro Ser 205

Ser Cys Asp Lys Thr 220

Leu Gly Gly Pro Ser

240

Leu Met Ile Ser Arg

255

- 313 044746

Thr Pro

Glu Val

260

Thr Cys

Val Val

Glu Val

Lys Phe 275

Asn Trp

Tyr Val

280

Lys Thr

290

Lys Pro

Arg Glu

Glu Gln

295

Ser Val

305

Leu Thr

Val Leu

310

His Gln

Val Asp 265

Asp Gly

Tyr Asn

Asp Trp

Val Ser

Val Glu

Ser Thr

300

Leu Asn 315

Lys Cys

Lys Val

Ser Asn

325

Lys Ala

Leu Pro

330

Ala Pro

Ile Ser

Lys Ala

340

Lys Gly

Glin Pro

Arg Glu 345

Pro Gln

Pro Pro

Ser Arg 355

Asp Glu

Leu Thr

360

Lys Asn

Gln Val

His Glu

270

Val His 285

Tyr Arg

Gly Lys

Ile Glu

Val Tyr

350

Ser Leu

365

Asp Pro

Asn Ala

Val Val

Glu Tyr

320

Lys Thr 335

Thr Leu

Thr Cys

Leu Val

370

Lys Gly

Phe Tyr

Pro Ser 375

Asp Ile

Ala Val

380

Glu Trp

Glu Ser

Asn Gly 385

Glin Pro

Glu Asn

390

Asn Tyr

Lys Thr

Thr Pro 395

Pro Val

Leu Asp

400

Ser Asp

Gly Ser

Phe Phe 405

Leu Tyr

Ser Lys

410

Leu Thr

Val Asp

Lys Ser 415

Arg Trp

Gln Gln

420

Gly Asn

Val Phe

Ser Cys 425

Ser Val

Met His

430

Glu Ala

Leu His

Asn His 435

Tyr Thr

Gln Lys

440

Ser Leu

Ser Leu

Ser Pro

445

Gly Lys <210> 313 <211> 645 <212> DNA <213> Artificial Sequence <220>

<223> Synthetic <400> 313 gacatccaga tgacccagtc tccatcctcc atcacgtgcc aggcgagtca ggacattaga gggaaagccc ctaagctcct gatctacgat ctgtccgcat ctgtaggaga cagagtcacc aactatttaa attggtatca gcagaaacca gcatccaatt tggaaacagg ggtcccatca

120

180

- 314 044746

aggttcagtg gaattggatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaagatattg caacatatta ctgtcaacag tatgataacc tccctatcac cttcggccaa 300 gggacacgac tggagattaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcaggggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 645

<210> 314 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>314

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Arg Asn Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ile Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Pro Ile 85 9095

Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys Arg Thr Val Ala Ala

100 105110

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

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

- 315 044746

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

145 150 155

Ser Gly Asn Ser Gln

160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

165 170

Thr Tyr Ser Leu Ser

175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

180 185

Lys His Lys Val Tyr 190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

195 200

Pro Val Thr Lys Ser

205

Phe Asn Arg Gly Glu Cys

210

315

351

DNA

Artificial

Synthetic

315 <210>

<211>

<212> <213>

<220> <223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca tactacggta sequence tggtggagtc cctctgggtt ggctggagtg agggccgatt gcctgagacc tggacgtctg tggaggaggc aaccgtcagt ggtctcagtt caccatctcc tgaggacacg gggccaaggg ttggt ccagc agcaactaca atttatagcg agacacaatt gccgtgtatt accacggtca cggggggggtc tgaactgggt gtggtagtaa ccaagaacac actgtacgcg ccgtctcctc cctgagactc ccgccaggtt attctacgta gctgtatctt agacgcgcaa a

120

180

240

300

351 <210> 316 <211> 117 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>316

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Leu Thr Val Ser Ser Asn 20 2530

Tyr Met Asn Trp Val Arg Gln Val Pro Gly Lys Gly Leu Glu Trp Val 35 4045

- 316 044746

Ser Val Ile Tyr 50

Ser Gly Gly Ser Lys Phe Tyr Val Asp

60

Ser Val Lys

Gly Arg Phe Thr 65

Ile Ser Arg His Asn Ser Lys Asn Thr

75

Leu Tyr Leu

Gln Met Asn Ser

Leu Arg Pro Glu Asp Thr Ala Val Tyr 85 90

Tyr Cys Thr 95

Arg Asp Ala Gln

100

Tyr Tyr Gly Met Asp Val Trp Gly Gln 105

Gly Thr Thr 110

Val Thr Val Ser Ser

115 <210> 317 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 317 gggttaaccg tcagtagcaa ctac <210> 318 <211> 21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 318 atttatagcg gtggtagtaa a <210> 319 <211> 7 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 319

Ile Tyr Ser Gly Gly Ser Lys

5

320 33 DNA <210>

<211>

<212>

- 317 044746 <213> Artificial sequence <220>

<223> Synthetic <400>320 acgcgagacg cgcaatacta cggtatggac gtc <210>321 <211>11 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>321

Thr Arg Asp Ala Gln Tyr Tyr Gly Met Asp Val 1 510 <210>322 <211>324 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 322 gacatccaga atcacttgcc ggagaagccc aggttcagtg gaagattttg caggggacca tgacccagtc gggcaagtca ctaagctcct gcagtggatc caacttacta agctggagat tccatcctcc gagcattagc gatctatgct tgggacagat ctgtcaacag ca aa ctgtctgcat acctatttac gcatccagtt ttcactctca agttacagta ctgtgggaga attggtatca tgcaaagtgg ccatcagcag cccctccgga cagagtcacc gcagaaacca ggtcccatca tctgcaacct gatttttggc

120

180

240

300

324 <210> 323 <211> 108 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>323

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Thr Tyr 20 2530

- 318 044746

Leu His Trp 35 Tyr Gln Gln Lys Pro 40 Gly Glu Ala Pro Lys 45 Leu Leu Ile Tyr Ala 50 Ala Ser Ser Leu Gln 55 Ser Gly Val Pro Ser 60 Arg Phe Ser Gly Ser 65 Gly Ser Gly Thr Asp 70 Phe Thr Leu Thr Ile 75 Ser Ser Leu Gln Pro 80 Glu Asp Phe Ala Thr 85 Tyr Tyr Cys Gln Gln 90 Ser Tyr Ser Thr Pro 95 Pro

Glu Ile Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100105 <210>324 <211>18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>324 cagagcatta gcacctat <210>325 <211>6 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>325

Gln Ser Ile Ser Thr Tyr <210>326 <211>30 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>326 caacagagtt acagtacccc tccggagatt <210>327 <211>10 <212> PROTEIN <213> Artificial sequence

- 319 044746 <220>

<223> Synthetic <400>327

Gln Gln Ser Tyr Ser Thr Pro Pro Glu Ile <210>328 <211>1344 <212> DNA <213> Artificial Sequence <220>

<223> Synthetic <400>328 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc cggggggggtc cctgagactc60 tcctgtgcag cctctgggtt aaccgtcagt agcaactaca tgaactgggt ccgccaggtt120 ccagggaagg ggctggagtg ggtctca gtt atttatagcg gtggtagtaa attctacgta180 gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt240 caaatgaaca gcctgagacc tgaggacacg gccgtgtatt actgtacgcg agacgcgcaa300 tactacggta tggacgtctg gggccaaggg acc acggtca ccgtctcctc agcctccacc360 aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacat ctgc600 aacgtgaatc acaagcccag caacaccaag gtggacaaga aagttgagcc caaatcttgt660 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc720 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggt caca780 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac840 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac900 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag960 tgcaaggtct ccaacaaagc cctcccagcc cccatcgaga aaaccatctc caaagccaaa1020 gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag1080 aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag1140 tgggagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc1200 gacggctcct tcttcctcta cagcaagctc accgtggaca agagcaggtg gcagcagggg1260 aacgtcttct catg ctccgt gatgcatgag gctctgcaca accactacac gcagaagtcc1320 ctctccctgt ctccgggtaa atga1344

- 320 044746 <210> 329 <211> 447 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 329

Glu Val Gln Leu Val

5

Glu Ser Gly Gly Gly

Leu Val Gln Pro Gly

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Leu Thr Val Ser Ser

Tyr Met Asn Trp Val 35

Arg Gln Val Pro Gly 40

Lys Gly Leu Glu Trp 45

Ser Val Ile Tyr Ser 50

Gly Gly Ser Lys Phe 55

Tyr Val Asp Ser Val 60

Gly Arg Phe Thr Ile 65

Ser Arg His Asn Ser 70

Lys Asn Thr Leu Tyr 75

Gln Met Asn Ser Leu

Arg Pro Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Asp Ala Gln Tyr

100

Tyr Gly Met Asp Val

105

Trp Gly Gln Gly Thr

110

Val Thr Val Ser Ser

115

Ala Ser Thr Lys Gly 120

Pro Ser Val Phe Pro

125

Ala Pro Ser Ser Lys 130

Ser Thr Ser Gly Gly

135

Thr Ala Ala Leu Gly

140

Leu Val Lys Asp Tyr 145

Phe Pro Glu Pro Val 150

Thr Val Ser Trp Asn 155

Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe

170

Pro Ala Val Leu Gln

175

Ser Gly Leu Tyr Ser

180

Leu Ser Ser Val Val

185

Thr Val Pro Ser Ser

190

Leu Gly Thr Gln Thr 195

Tyr Ile Cys Asn Val 200

Asn His Lys Pro Ser 205

Gly

Asn

Val

Lys

Leu 80

Thr

Thr

Leu

Cys

Ser 160

Ser

Ser

Asn

- 321 044746

Thr Lys Val Asp Lys

210

Lys Val Glu Pro Lys

215

Ser Cys Asp Lys Thr

220

Thr Cys Pro Pro Cys 225

Pro Ala Pro Glu Leu 230

Leu Gly Gly Pro Ser 235

Phe Leu Phe Pro Pro

245

Lys Pro Lys Asp Thr

250

Leu Met Ile Ser Arg

255

Pro Glu Val Thr Cys

260

Val Val Val Asp Val

265

Ser His Glu Asp Pro

270

Val Lys Phe Asn Trp

275

Tyr Val Asp Gly Val

280

Glu Val His Asn Ala

285

Thr Lys Pro Arg Glu

290

Glu Gln Tyr Asn Ser

295

Thr Tyr Arg Val Val

300

Val Leu Thr Val Leu 305

His Gln Asp Trp Leu 310

Asn Gly Lys Glu Tyr 315

Cys Lys Val Ser Asn

325

Lys Ala Leu Pro Ala

330

Pro Ile Glu Lys Thr

335

Ser Lys Ala Lys Gly

340

Gln Pro Arg Glu Pro

345

Gln Val Tyr Thr Leu

350

Pro Ser Arg Asp Glu

355

Leu Thr Lys Asn Gln 360

Val Ser Leu Thr Cys 365

Val Lys Gly Phe Tyr

370

Pro Ser Asp Ile Ala

375

Val Glu Trp Glu Ser

380

Gly Gln Pro Glu Asn 385

Asn Tyr Lys Thr Thr 390

Pro Pro Val Leu Asp 395

Asp Gly Ser Phe Phe

405

Leu Tyr Ser Lys Leu

410

Thr Val Asp Lys Ser

415

Trp Gln Gln Gly Asn

420

Val Phe Ser Cys Ser

425

Val Met His Glu Ala

430

His

Val 240

Thr

Glu

Lys

Ser

Lys 320

Ile

Pro

Leu

Asn

Ser 400

Arg

Leu

His Asn His Tyr Thr 435

Gln Lys Ser Leu Ser 440

Leu Ser Pro Gly Lys 445 <210> 330 <211> 648

- 322 044746 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>330 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtgggaga cagagtcacc60 atcacttgcc gggcaagtca gagcattagc acctatttac attggtatca gcagaaacca120 ggagaagccc ctaagctcct gatctatgct gcatccagtt tgcaa agtgg ggtcccatca180 aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct240 gaagattttg caacttacta ctgtcaacag agttacagta cccctccgga gatttttggc300 caggggacca agctggagat caaacgaact gtggctgcac catctgt ctt catcttcccg360 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc420 tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc480 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg540 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag600 ggcctga gct cgcccgtcac aaagagcttc aacaggggag agtgttag648 <210>331 <211>215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>331

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Thr Tyr 20 2530

Leu His Trp Tyr Gln Gln Lys Pro Gly Glu Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro 85 9095

- 323 044746

Glu Ile

Phe Gly

100

Gln Gly

Thr Lys

Ala Pro

Ser Val 115

Phe Ile

Phe Pro

120

Gly Thr

130

Ala Ser

Val Val

Cys Leu 135

Ala Lys 145

Val Gln

Trp Lys

150

Val Asp

Gln Glu

Ser Val

Thr Glu 165

Gln Asp

Ser Ser

Thr Leu

180

Thr Leu

Ser Lys

Tyr Ala

Cys Glu 195

Val Thr

His Gln

200

Leu Glu 105

Pro Ser

Leu Asn

Asn Ala

Ser Lys 170

Ala Asp 185

Gly Leu

Ile Lys

Asp Glu

Asn Phe

140

Leu Gln 155

Asp Ser

Tyr Glu

Ser Ser

Ser Phe Asn Arg Gly Glu

210

Cys 215

Arg Thr

110

Gln Leu 125

Tyr Pro

Ser Gly

Thr Tyr

Lys His

190

Pro Val 205

Val Ala

Lys Ser

Arg Glu

Asn Ser

160

Ser Leu 175

Lys Val

Thr Lys <210>

<211>

<212>

<213>

332

354

DNA

Artificial sequence

Synthetic

332 <220>

<223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca gttcggggcg tggtggagtc cctctgggat ggctggagtg agggccgatt acctgagagc gtatggacgt tggaggaggc caccgtcagt ggtctcagtt caccatctcc tgaggacacg ctggggccaa tt ggtccagc agcaattaca atttatagcg agacacaatt gccgtgtatt gggaccacgg ctggggggtc tgacctgggt gtggtagcac ccaagaacac actgtgtgag tcaccgtctc cctgagactc ccgccaggct attctacgca gctgtatctt agatctagag ctca

120

180

240

300

354 <210> 333 <211> 118 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic

- 324 044746 <400>333

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ile Thr Val Ser Ser Asn 20 2530

Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Asn Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Val 85 9095

Arg Asp Leu Glu Val Arg Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105110

Thr Val Thr Val Ser Ser

115 <210>334 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>334 gggatcaccg tcagtagcaa ttac <210>335 <211>36 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>335 gtgagagatc tagaggttcg gggcggtatg gacgtc <210>336 <211>12 <212> PROTEIN <213> Artificial sequence

- 325 044746 <220>

<223> Synthetic <400> 336

Val Arg Asp Leu Glu Val Arg Gly Gly Met Asp Val 1 5 10 <210> 337 <211> 324 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 337 gaaattgtgt ctctcctgca cctggccagg gacaggttca cctgaagatt caagggacca tgacgcagtc gggccagtca ctcccaggct gtggcagtgg ttgcagtgta aggtggaaat tccaggcacc gagttttagc cctcatctat gtctgggaca ttact gtcag caaa ctgtctttgt agcagctact ggtgcatcca gacttcactc cagtatggta ctccagggga tagcctggta gcagggccac tcaccatcag gctcaccttg aagagccacc ccagcagaaa tggcatccca cagactggag gacgttcggc

120

180

240

300

324 <210> 338 <211> 108 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 338

Glu Ile 1

Val Leu

Thr Gln 5

Ser Pro

Gly Thr

Leu Ser

Leu Ser

Glu Arg

Ala Thr

Leu Ser

CysArg

Ala Ser 25

Gln Ser

Phe Ser

Tyr Leu

Ala Trp 35

Tyr Gln

Gln Lys

Pro Gly

Gln Ala

Pro Arg 45

Ile Tyr

Gly Ala

Ser Ser

Arg Ala 55

Thr Gly

Ile Pro

Asp Arg

Gly Ser 65

Gly Ser

Gly Thr 70

Asp Phe

Thr Leu

Thr Ile 75

Ser Arg

Pro Glu

Asp Phe

Ala Val 85

Tyr Tyr

Cys Gln 90

Gln Tyr

Gly Ser

Pro Gly 15

Ser Ser

Leu Leu

Phe Ser

Leu Glu 80

Ser Pro 95

- 326 044746

Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100105 <210>339 <211>21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>339 cagagtttta gcagcagcta c21 <210>340 <211>7 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>340

Gln Ser Phe Ser Ser Ser Tyr 15 <210>341 <211>1347 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 341 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctgggat caccgtcagt agcaattaca tgacctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca acctgagagc tgaggacacg gccgtgtatt actgtgtgag agatctagag 300 gttcggggcg gtatggacgt ctggggccaa gggaccacgg tcaccgtctc ctcagcctcc 360 accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tggggggcaca 420 gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540 tactccctca gcagcgtggt gaccgtgccc tccagcagct tggggcacca gacctacatc 600 tgcaacgtga atcacaagcc cagcaacacc aaggtggac agaaagttga gcccaaatct 660

- 327 044746 tgtgacaaaa gtcttcctct acatgcgtgg gacggcgtgg taccgtgtgg aagtgcaagg aaagggcagc aagaaccagg gagtgggaga tccgacggct gggaacgtct tccctctccc ctcacacatg tccccccaaa tggtggacgt aggtgcataa tcagc gtcct tctccaacaa cccgagaacc tcagcctgac gcaatgggca ccttcttcct tctcatgctc tgtctccggg cccaccgtgc acccaaggac gagccacgaa tgccaagaca caccgtcctg agccctccca acaggtgtac ctgcctggtc gccggagaac ctacagcaag cgtgatgcat taaatga ccagcacctg accctcatga gaccctgagg aagccgcggg caccaggact gcccccatcg accctgcccc aaaggcttct aactacaaga ctcaccgtgg gaggctctgc aactcctggg tctcccggac tcaagttcaa aggagcagta ggctgaatgg agaaaaccat catcccggga atcccagcga ccacgcctcc acaagagcag acaaccacta gggaccgtca ccctgaggtc ctggtacgtg caacagcacg caaggagtac ctccaaagcc tgagctgacc catcgccgtg cgtg ctggac gtggcagcag cacgcagaag

720

780

840

900

960

1020

1080

1140

1200

1260

1320

1347 <210> 342 <211> 448 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 342

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Ile Thr Val Ser Ser Asn 25 30

Tyr Met Thr Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Ser Gly Gly Ser

55

Thr Phe Tyr Ala Asp Ser Val Lys 60

Gly Arg Phe Thr Ile Ser Arg His 65 70

Asn Ser Lys Asn Thr Leu Tyr Leu

80

Gln Met Asn Asn Leu Arg Ala Glu 85

Asp Thr Ala Val Tyr Tyr Cys Val

95

Arg Asp Leu Glu Val Arg Gly Gly

100

Met Asp Val Trp Gly Gln Gly Thr

105 110

- 328 044746

Thr

Leu

Cys 145

Ser

Ser

Ser

Asn

His 225

Val

Thr

Glu

Lys

Ser 305

Lys

Ile

Pro

Val Thr Val

115

Ala Pro Ser 130

Leu Val Lys

Gly Ala Leu

Ser Gly Leu

180

Leu Gly Thr

195

Thr Lys Val 210

Thr Cys Pro

Phe Leu Phe

Pro Glu Val

260

Val Lys Phe

275

Thr Lys Pro 290

Val Leu Thr

Cys Lys Val

Ser Lys Ala

340

Pro Ser Arg

355

Ser Ser Ala

Ser Lys Ser

135

Asp Tyr Phe

150

Thr Ser Gly 165

Tyr Ser Leu

Gln Thr Tyr

Asp Lys Lys

215

Pro Cys Pro

230

Pro Pro Lys 245

Thr Cys Val

Asn Trp Tyr

Arg Glu Glu

295

Val Leu His

310

Ser Asn Lys 325

Lys Gly Gln

Asp Glu Leu

Ser Thr Lys 120

Thr Ser Gly

Pro Glu Pro

Val His Thr

170

Ser Ser Val

185

Ile Cys Asn 200

Val Glu Pro

Ala Pro Glu

Pro Lys Asp

250

Val Val Asp

265

Val Asp Gly 280

Gln Tyr Asn

Gln Asp Trp

Ala Leu Pro

330

Pro Arg Glu

345

Thr Lys Asn 360

Gly Pro Ser

125

Gly Thr Ala

140

Val Thr Val 155

Phe Pro Ala

Val Thr Val

Val Asn His

205

Lys Ser Cys

220

Leu Leu Gly 235

Thr Leu Met

Val Ser His

Val Glu Val

285

Ser Thr Tyr

300

Leu Asn Gly 315

Ala Pro Ile

Pro Gln Val

Gln Val Ser

365

Val Phe Pro

Ala Leu Gly

Ser Trp Asn

160

Val Leu Gln

175

Pro Ser Ser 190

Lys Pro Ser

Asp Lys Thr

Gly Pro Ser

240

Ile Ser Arg

255

Glu Asp Pro 270

His Asn Ala

Arg Val Val

Lys Glu Tyr

320

Glu Lys Thr

335

Tyr Thr Leu 350

Leu Thr Cys

- 329 044746

Leu Val 370 Lys Gly Phe Tyr Pro 375 Ser Asp Ile Ala Val 380 Glu Trp Glu Ser Asn 385 Gly Gln Pro Glu Asn 390 Asn Tyr Lys Thr Thr 395 Pro Pro Val Leu Asp 400 Ser Asp Gly Ser Phe 405 Phe Leu Tyr Ser Lys 410 Leu Thr Val Asp Lys 415 Ser Arg Trp Gln Gln 420 Gly Asn Val Phe Ser 425 Cys Ser Val Met His 430 Glu Ala Leu His Asn 435 His Tyr Thr Gln Lys 440 Ser Leu Ser Leu Ser 445 Pro Gly Lys

<210> 343 <211> 648 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>343 gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc60 ctctcctgca gggccagtca gagttttagc agcagctact tagcctggta ccagcagaaa120 cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca180 gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag240 cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccttg gacgttcggc300 caagggacca aggtggaaat caaacgaact gtggctgcac cat ctgtctt catcttcccg360 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc420 tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc480 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg540 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag600 ggcctga gct cgcccgtcac aaagagcttc aacaggggag agtgttag648 <210>344 <211>215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 344

- 330 044746

Glu Ile Val Leu Thr

5

Gln Ser Pro Gly Thr

Leu Ser Leu Ser Pro

Glu Arg Ala Thr Leu

Ser Cys Arg Ala Ser

Gln Ser Phe Ser Ser

Tyr Leu Ala Trp Tyr 35

Gln Gln Lys Pro Gly 40

Gln Ala Pro Arg Leu 45

Ile Tyr Gly Ala Ser 50

Ser Arg Ala Thr Gly 55

Ile Pro Asp Arg Phe 60

Gly Ser Gly Ser Gly 65

Thr Asp Phe Thr Leu 70

Thr Ile Ser Arg Leu 75

Pro Glu Asp Phe Ala 85

Val Tyr Tyr Cys Gln 90

Gln Tyr Gly Ser Ser 95

Trp Thr Phe Gly Gln

100

Gly Thr Lys Val Glu

105

Ile Lys Arg Thr Val

110

Ala Pro Ser Val Phe

115

Ile Phe Pro Pro Ser

120

Asp Glu Gln Leu Lys 125

Gly Thr Ala Ser Val 130

Val Cys Leu Leu Asn

135

Asn Phe Tyr Pro Arg 140

Ala Lys Val Gln Trp 145

Lys Val Asp Asn Ala 150

Leu Gln Ser Gly Asn 155

Gln Glu Ser Val Thr

165

Glu Gln Asp Ser Lys

170

Asp Ser Thr Tyr Ser

175

Ser Ser Thr Leu Thr

180

Leu Ser Lys Ala Asp

185

Tyr Glu Lys His Lys

190

Tyr Ala Cys Glu Val 195

Thr His Gln Gly Leu 200

Ser Ser Pro Val Thr

205

Gly

Ser

Leu

Ser

Glu 80

Pro

Ala

Ser

Glu

Ser 160

Leu

Val

Lys

Ser Phe Asn Arg Gly

210

Glu Cys

215 <210> 345 <211> 1329 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic

- 331 044746

<400> 345 gaggtgcagc tggtggagtc tggaggaggc ttggtccagt ctggggggtc cctgagactc 60 tcctgtgcag cctctggggct caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg gactggagtg ggtctcagtt atttatagcg gtggtagcac attctactca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agcgagggga 300 gacgcttttg atatctgggg ccaagggaca atggtcaccg tctcttcagc ctccaccaag 360 ggcccatcgg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 420 ctggggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 480 gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 540 ctcagcagcg tggtgaccgt gccctccagc agcttggggca cgaagaccta cacctgcaac 600 gtagatcaca agccagcaa caccaaggtg gacaagag ttgagtccaa atatggtccc 660 ccatgcccac cgtgcccagc accaggcggt ggcggaccat cagtcttcct gttcccccca 720 aaacccaagg acactctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 780 gtgagccagg aagaccccga ggtccagttc aactggtacg tggatggcgt ggaggtgcat 840 aatgccaaga caaagccgcg ggagaggagcag ttcaacagca cgtaccgtgt ggtcagcgtc 900 ctcaccgtcc tgcaccagga ctggctgaac ggcaagggagt acaagtgcaa ggtctccaac 960 aaaggcctcc cgtcctccat cgagaaaacc atctccaaag ccaaagggca gccccgagag 1020 ccacaggtgt acaccctgcc cccaccag gaggagatga ccaagaacca ggtcagcctg 1080 acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg 1140 cagccggaga acaactacaa gaccacgcct cccgtgctgg actccgacgg ctccttcttc 1200 ctctacagca ggctcaccgt ggacaagagc aggtggcagg aggggaatgt cttctcatgc 1260 tccgtgatgc atgaggctct gcacaaccac tacacacaga agtccctctc cctgtctctg 1320

ggtaaatga 1329 <210> 346 <211> 442 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 346

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ser Gly Gly

5 10 15

- 332 044746

Ser Leu Arg Leu Ser Cys Ala Ala 20

Tyr Met Ser Trp Val Arg Gln Ala 35 40

Ser Gly Leu 25

Pro Gly Lys

Thr Val Ser Ser Asn

Gly Leu Glu Trp Val 45

Ser Val Ile Tyr 50

Gly Arg Phe Thr 65

Ser Gly Gly Ser Thr Phe 55

Ile Ser Arg His Asn Ser 70

Tyr Ser Asp Ser Val Lys 60

Lys Asn Thr Leu Tyr Leu 75 80

Gln Met Asn

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

90 95

Arg

Ala

Arg

Gly 100

Asp

Ala

Phe

Asp

Ile

105

Trp

Gly

Gln

Gly

Thr

110

Met

Val

Thr

Val

Ser

115

Ser

Ala

Ser

Thr

Lys 120

Gly

Pro

Ser

Val

Phe

125

Pro

Leu

Ala

Pro

Cys 130

Ser

Arg

Ser

Thr

Ser

135

Glu

Ser

Thr

Ala

Ala

140

Leu

Gly

Cys

Leu

Val Lys Asp 145

Ala Leu Thr

Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn 150 155

Ser Gly Val His Thr Phe Pro Ala Val Leu Gln 165 170

Ser

Ser

175

Gly Leu

Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

180 185

Gly Thr

Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro

195 200 205

Lys Val 210 Asp Lys Arg Val Glu 215 Ser Lys Cys 225 Pro Ala Pro Gly Gly 230 Gly Gly Pro

Lys Pro Lys Asp Thr Leu Met Ile

245

Val Val Val Asp Val Ser Gln Glu

260

Gly 160

Ser

Ser Ser Leu 190

Ser Asn Thr

Tyr Gly Pro Pro Cys Pro Pro 220

Ser Val Phe Leu Phe Pro Pro

235 240

Ser Arg

250

Thr Pro

Asp Pro 265

Glu Val

Glu Val Thr Cys

255

Gln Phe Asn Trp

270

- 333 044746

Tyr

Val

Asp 275

Gly

Val

Glu

Val

His

280

Asn

Ala

Lys

Thr

Lys

285

Pro

Arg

Glu

Glu

Gln 290

Phe

Asn

Ser

Thr

Tyr 295

Arg

Val

Val

Ser

Val

300

Leu

Thr

Val

Leu

His

305

Gln

Asp

Trp

Leu

Asn

310

Gly

Lys

Glu

Tyr

Lys 315

Cys

Lys

Val

Ser

Asn

320

Lys

Gly

Leu

Pro

Ser

325

Ser

Ile

Glu

Lys

Thr

330

Ile

Ser

Lys

Ala

Lys

335

Gly

Gln

Pro

Arg

Glu

340

Pro

Gln

Val

Tyr

Thr

345

Leu

Pro

Pro

Ser

Gln

350

Glu

Glu

Met

Thr

Lys

355

Asn

Gln

Val

Ser

Leu

360

Thr

Cys

Leu

Val

Lys 365

Gly

Phe

Tyr

Pro

Ser

370

Asp

Ile

Ala

Val

Glu

375

Trp

Glu

Ser

Asn

Gly 380

Gln

Pro

Glu

Asn

Asn

385

Tyr

Lys

Thr

Thr

Pro

390

Pro

Val

Leu

Asp

Ser

395

Asp

Gly

Ser

Phe

Phe

400

Leu

Tyr

Ser

Arg

Leu

405

Thr

Val

Asp

Lys

Ser

410

Arg

Trp

Gln

Glu

Gly 415

Asn

Val

Phe

Ser

Cys 420

Ser

Val

Met

His

Glu

425

Ala

Leu

His

Asn

His

430

Tyr

Thr

Gln

Lys

Ser

435

Leu

Ser

Leu

Ser

Leu

440

Gly

Lys <210> 347 <211> 1341 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 347

caggtgcagc tggtggagtc tgggggaggc ttggtcaagc ctggagggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagt gactactaca tgagctggat ccgccaggct 120 ccagggaagg ggctggagtg ggtttcatac attacktata gtggtagtac catatactac 180 gcagactctg tgaagggccg attcaccatc tccagggaca acgccaagag ctcactgtat 240 ctgcaaatga acagcctgag agccgaggac acggccgtgt attackgtgc gagagatcgc 300

- 334 044746

ggtacaacta tggtcccctt tgactactgg ggccagggaa ccctggtcac cgtctcctca 360 gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 420 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacgaagacc 600 tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 660 aaatatggtc ccccatgccc accgtgccca gcaccaggcg gtggcggacc atcagtcttc 720 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 780 gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 840 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cagtaccgt 900 gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 960 aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1020 cagccccgag agccacaggt gtacaccctg ccccatccc aggaggat gaccaagaac 1080 caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1140 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1200 ggctccttct tcctctacag caggctcacc gtggacaaga gcaggtggca ggaggggaat 1260 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagtccctc 1320 tccctgtctc tgggtaaatg a 1341

<210> 348 <211> 446 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 348

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Lys Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Ser Asp Tyr 25 30

Tyr Met Ser Trp Ile Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Tyr Ile Thr Tyr Ser Gly Ser

55

Thr Ile Tyr Tyr Ala Asp Ser Val 60

- 335 044746

Lys 65

Leu

Ala

Gly

Phe

Leu 145

Trp

Leu

Ser

Pro

Pro 225

Leu

Glu

Gln

Lys

Leu 305

Gly Arg Phe

Gln Met Asn

Arg Asp Arg

100

Thr Leu Val

115

Pro Leu Ala 130

Gly Cys Leu

Asn Ser Gly

Gln Ser Ser

180

Ser Ser Leu

195

Ser Asn Thr 210

Cys Pro Pro

Phe Pro Pro

Val Thr Cys

260

Phe Asn Trp

275

Pro Arg Glu 290

Thr Val Leu

Thr Ile Ser

Ser Leu Arg 85

Gly Thr Thr

Thr Val Ser

Pro Cys Ser

135

Val Lys Asp

150

Ala Leu Thr 165

Gly Leu Tyr

Gly Thr Lys

Lys Val Asp

215

Cys Pro Ala

230

Lys Pro Lys 245

Val Val Val

Tyr Val Asp

Glu Gln Phe

295

His Gln Asp

310

Arg Asp Asn

Ala Glu Asp

Met Val Pro

105

Ser Ala Ser 120

Arg Ser Thr

Tyr Phe Pro

Ser Gly Val

170

Ser Leu Ser

185

Thr Tyr Thr 200

Lys Arg Val

Pro Gly Gly

Asp Thr Leu

250

Asp Val Ser

265

Gly Val Glu 280

Asn Ser Thr

Trp Leu Asn

Ala Lys Ser 75

Thr Ala Val

Phe Asp Tyr

Thr Lys Gly

125

Ser Glu Ser

140

Glu Pro Val 155

His Thr Phe

Ser Val Val

Cys Asn Val

205

Glu Ser Lys

220

Gly Gly Pro 235

Met Ile Ser

Gln Glu Asp

Val His Asn

285

Tyr Arg Val

300

Gly Lys Glu 315

Ser Leu Tyr

Tyr Tyr Cys 95

Trp Gly Gln 110

Pro Ser Val

Thr Ala Ala

Thr Val Ser

160

Pro Ala Val

175

Thr Val Pro 190

Asp His Lys

Tyr Gly Pro

Ser Val Phe

240

Arg Thr Pro

255

Pro Glu Val 270

Ala Lys Thr

Val Ser Val

Tyr Lys Cys

320

- 336 044746

Lys Val

Ser Asn

Lys Ala

Lys Gly

340

Ser Gln

Glu Glu 355

Lys Gly

370

Phe Tyr

Gln Pro 385

Glu Asn

Gly Ser

Phe Phe

Gln Glu

Gly Asn

420

Asn His

Tyr Thr 435

Lys Gly 325

Glin Pro

Met Thr

Pro Ser

Asn Tyr 390

Leu Tyr 405

Val Phe

Gln Lys

Leu Pro

Arg Glu

Lys Asn

360

Asp Ile 375

Lys Thr

Ser Arg

Ser Cys

Ser Leu

440

Ser Ser

330

Pro Gln 345

Gln Val

Ala Val

Thr Pro

Leu Thr

410

Ser Val

425

Ser Leu <210> 349 <211> 1341 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 349 gaggtgcagc tcctgtgcag ccagggaagg gactacgccg ctgtatctac gcgaggtggg gcctccacca agcacagccg tggaactcag ggactctact tggtggagtc cctctggaat ggctggagtg cacccgtgaa aaatgaacag actggtactt agg gcccatc ccctgggctg gcgccctgac ccctcagcag tgggggaggc cactttcagt ggttggccgt aggcagattc cctgaaaacc cgatctctgg ggtcttcccc cctggtcaag cagcggcgtg cgtggtgacc

Ile Glu

Val Tyr

Ser Leu

Glu Trp

380

Pro Val 395

Val Asp

Met His

Ser Leu ttggtaaagc aacgcctgga attaaaagca accatctcaa gaggacag ggccgtggca ctggcgccct gactacttcc cacaccttcc gtgccctcca

Lys Thr

Thr Leu

350

Thr Cys 365

Glu Ser

Leu Asp

Lys Ser

Glu Ala

430

Gly Lys 445 ctggggggtc tgagttgggt aaactgatgg gagatgattc ccgtgtatta ccctggtcac gctccaggag ccgaaccggt cggctgtcct gcagcttggg

Ile Ser 335

Pro Pro

Leu Val

Asn Gly

Ser Asp 400

Arg Trp 415

Leu His ccttagactc ccgccaggct tgggacaaca aaaaaacacg ctgtaccaca tgtctcctca cacctccgag gacggtgtcg acagtcctca cacgaagacc

120

180

240

300

360

420

480

540

600

- 337 044746

tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 660 aaatatggtc ccccatgccc accgtgccca gcaccaggcg gtggcggacc atcagtcttc 720 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 780 gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 840 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cagtaccgt 900 gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 960 aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1020 cagccccgag agccacaggt gtacaccctg ccccatccc aggaggat gaccaagaac 1080 caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1140 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1200 ggctccttct tcctctacag caggctcacc gtggacaaga gcaggtggca ggaggggaat 1260 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagtccctc 1320 tccctgtctc tgggtaaatg a 1341

<210> 350 <211> 446 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 350

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Lys Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Ile Thr Phe Ser Asn Ala 25 30

Trp Met Ser Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Gly Arg Ile Lys Ser Lys Thr Asp

55

Gly Gly Thr Thr Asp Tyr Ala Ala 60

Pro Val Lys Gly Arg Phe Thr Ile 65 70

Ser Arg Asp Asp Ser Lys Asn Thr

80

Leu Tyr Leu Gln Met Asn Ser Leu 85

Lys Thr Glu Asp Thr Ala Val Tyr

95

Tyr Cys Thr Thr Ala Arg Trp Asp

100

Trp Tyr Phe Asp Leu Trp Gly Arg

105 110

- 338 044746

Gly Thr Leu 115 Val Thr Val Ser Ser 120 Ala Ser Thr Lys Gly 125 Pro Ser Val Phe Pro 130 Leu Ala Pro Cys Ser 135 Arg Ser Thr Ser Glu 140 Ser Thr Ala Ala Leu 145 Gly Cys Leu Val Lys 150 Asp Tyr Phe Pro Glu 155 Pro Val Thr Val Ser 160 Trp Asn Ser Gly Ala 165 Leu Thr Ser Gly Val 170 His Thr Phe Pro Ala 175 Val Leu Gln Ser Ser 180 Gly Leu Tyr Ser Leu 185 Ser Ser Val Val Thr 190 Val Pro Ser Ser Ser 195 Leu Gly Thr Lys Thr 200 Tyr Thr Cys Asn Val 205 Asp His Lys Pro Ser 210 Asn Thr Lys Val Asp 215 Lys Arg Val Glu Ser 220 Lys Tyr Gly Pro Pro 225 Cys Pro Pro Cys Pro 230 Ala Pro Gly Gly Gly 235 Gly Pro Ser Val Phe 240 Leu Phe Pro Pro Lys 245 Pro Lys Asp Thr Leu 250 Met Ile Ser Arg Thr 255 Pro Glu Val Thr Cys 260 Val Val Val Asp Val 265 Ser Gln Glu Asp Pro 270 Glu Val Gln Phe Asn 275 Trp Tyr Val Asp Gly 280 Val Glu Val His Asn 285 Ala Lys Thr Lys Pro 290 Arg Glu Glu Gln Phe 295 Asn Ser Thr Tyr Arg 300 Val Val Ser Val Leu 305 Thr Val Leu His Gln 310 Asp Trp Leu Asn Gly 315 Lys Glu Tyr Lys Cys 320 Lys Val Ser Asn Lys 325 Gly Leu Pro Ser Ser 330 Ile Glu Lys Thr Ile 335 Ser Lys Ala Lys Gly 340 Gln Pro Arg Glu Pro 345 Gln Val Tyr Thr Leu 350 Pro Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

- 339 044746

355 360 365

Lys Gly Phe Tyr

370

Pro Ser Asp Ile

375

Ala Val Glu Trp

380

Glu Ser Asn Gly

Gln Pro Glu Asn 385

Asn Tyr Lys Thr 390

Thr Pro Pro Val

395

Leu Asp Ser Asp

400

Gly Ser Phe Phe

Leu Tyr Ser Arg 405

Leu Thr Val Asp 410

Lys Ser Arg Trp

415

Gln Glu Gly Asn

420

Val Phe Ser Cys

Ser Val Met His 425

Glu Ala Leu His

430

Asn His Tyr Thr

435

Gln Lys Ser Leu

440

Ser Leu Ser Leu

Gly Lys 445

<210> 351 <211> 1341 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 351 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcactt atttatagcg gtggtagcac atactatgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagatc tgaggacacg gccgtgtatt actgtgcgag agtccccctg 300 ggggattact actacggtat ggacgtctgg ggccaaggga ccacggtcac cgtctcctca 360 gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 420 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacgaagacc 600 tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 660 aaatatggtc ccccatgccc accgtgccca gcaccaggcg gtggcggacc atcagtcttc 720 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 780 gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 840 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cagtaccgt 900 gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 960

- 340 044746 aaggtctcca cagccccgag caggtcagcc gagagcaatg ggctccttct gtcttctcat tccctgtctc acaaaggcct agccacaggt tgacctgcct ggcagccgga tcctctacag gctccgtgat tgggtaaatg cccgtcctcc gtacaccctg ggtcaaa ggc gaacaactac caggctcacc gcatgaggct a atcgagaaaa cccccatccc ttctacccca aagaccacgc gtggacaaga ctgcacaacc ccatctccaa aggaggagat gcgacatcgc ctcccgtgct gcaggtggca actacacaca agccaaaggg gaccaagaac cgtggagtgg ggactccgac ggaggggaat gaagtccctc

1020

1080

1140

1200

1260

1320

1341 <210> 352 <211> 446 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 352

Glu Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly 10

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Tyr Met

Ser Trp 35

Val Arg

Gln Ala

Pro Gly

Ser Leu

Ile Tyr

Ser Gly

Gly Ser 55

Thr Tyr

Gly Arg 65

Phe Thr

Ile Ser

Arg His

Asn Ser

Gln Met

Asn Ser

Leu Arg 85

Ser Glu

Asp Thr

Arg Val

Gly Thr

Phe Pro

130

Leu Gly

ProLeu

100

Gly Asp

Tyr Tyr

Tyr Gly 105

Thr Val 115

Thr Val

Ser Ser

120

Ala Ser

Leu Ala

Cys Leu

Pro Cys

Ser Arg 135

Ser Thr

Val Lys

Asp Tyr

Phe Pro

Leu Val

Phe Thr

Lys Gly

Tyr Ala 60

Lys Asn 75

Ala Val

Met Asp

Thr Lys

Ser Glu

140

Glu Pro

Glin Pro

Val Ser

Leu Glu 45

Asp Ser

Gly Gly 15

Ser Asn

Trp Val

Val Lys

Thr Leu

Tyr Tyr

Val Trp

110

Gly Pro 125

Ser Thr

Val Thr

Tyr Leu 80

Cys Ala 95

Gly Gln

Ser Val

Ala Ala

Val Ser

- 341 044746

145

150

155

Trp Asn Ser Gly Ala

165

Leu Thr Ser Gly Val

170

His Thr Phe Pro Ala

175

Leu Gln Ser Ser Gly

180

Leu Tyr Ser Leu Ser

185

Ser Val Val Thr Val

190

Ser Ser Ser Leu Gly 195

Thr Lys Thr Tyr Thr 200

Cys Asn Val Asp His

205

Pro Ser Asn Thr Lys 210

Val Asp Lys Arg Val

215

Glu Ser Lys Tyr Gly 220

Pro Cys Pro Pro Cys 225

Pro Ala Pro Gly Gly 230

Gly Gly Pro Ser Val 235

Leu Phe Pro Pro Lys

245

Pro Lys Asp Thr Leu

250

Met Ile Ser Arg Thr

255

Glu Val Thr Cys Val

260

Val Val Asp Val Ser

265

Gln Glu Asp Pro Glu

270

Gln Phe Asn Trp Tyr

275

Val Asp Gly Val Glu

280

Val His Asn Ala Lys

285

Lys Pro Arg Glu Glu

290

Gln Phe Asn Ser Thr

295

Tyr Arg Val Val Ser 300

Leu Thr Val Leu His 305

Gln Asp Trp Leu Asn 310

Gly Lys Glu Tyr Lys 315

Lys Val Ser Asn Lys

325

Gly Leu Pro Ser Ser

330

Ile Glu Lys Thr Ile

335

Lys Ala Lys Gly Gln

340

Pro Arg Glu Pro Gln

345

Val Tyr Thr Leu Pro

350

Ser Gln Glu Glu Met

355

Thr Lys Asn Gln Val

360

Ser Leu Thr Cys Leu

365

Lys Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val

375

Glu Trp Glu Ser Asn

380

Gln Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro 390

Pro Val Leu Asp Ser 395

160

Val

Pro

Lys

Pro

Phe 240

Pro

Val

Thr

Val

Cys 320

Ser

Pro

Val

Gly

Asp 400

- 342 044746

Gly Ser Phe Phe

Leu Tyr Ser Arg 405

Leu Thr Val Asp 410

Lys Ser Arg Trp

415

Gln Glu Gly Asn

420

Val Phe Ser Cys

Ser Val Met His 425

Glu Ala Leu His

430

Asn His Tyr Thr

435

Gln Lys Ser Leu

440

Ser Leu Ser Leu

Gly Lys 445 <210> 353 <211> 1353 <212> DNA <213> Artificial sequence

<220> <223> Synthetic <400> 353 caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgtgcag cgtctggatt caccttcaga aactatggca tgcactgggt ccgccaggct 120 ccaggcaagg ggctggagtg ggtgtcagtt atatggtatg atggaagtaa tagatactat 180 gcagactccg tgaagggccg attcaccatc tccagagaca cttccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agccgaagac acggctgtgt attackgtgc gagagatcct 300 cctataactg gaacgacggg gggcgatgct tttgatatct ggggccaagg gacaatggtc 360 accgtctctt cagcctccac caagggccca tcggtcttcc ccctggcgcc ctgctccagg 420 agcacctccg agagcacagc cgccctggggc tgcctggtca aggactactt ccccgaaccg 480 gtgacggtgt cgtggaactc aggcgccctg accagcggcg tgcacacctt cccggctgtc 540 ctacagtcct caggactcta ctccctcagc agcgtggtga ccgtgccctc cagcagcttg 600 ggcacgaaga cctacacctg caacgtagat cacaagccca gcaacaccaa ggtggacag 660 agagttgagt ccaaatatgg tcccccatgc ccaccgtgcc cagcaccagg cggtggcgga 720 ccatcagtct tcctgttccc cccaaaaccc aaggacactc tcatgatctc ccggacccct 780 gaggtcacgt gcgtggtggt ggacgtgagc caggaagacc ccgaggtcca gttcaactgg 840 tacgtggatg gcgtggaggt gcataatgcc aagacaaagc cgcggggaga gcagttcaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaacggcaag 960 gagtacaagt gcaaggtctc caacaaaggc ctcccgtcct ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agagccacag gtgtacacc tgcccccatc ccaggagag 1080 atgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctaccc cagcgacatc 1140 gccgtggagt ggggagagcaa tggggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctctac agcaggctca ccgtggacaa gagcaggtgg 1260

- 343 044746 caggagggga atgtcttctc atgctccgtg atgcatgagg ctctgcacaa cactacaca

1320

1353 cagaagtccc tctccctgtc tctgggtaaa tga <210> 354 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 354

Gln Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly 10

Val Val

Glin Pro

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Phe Thr

Phe Arg 30

Gly Met

His Trp 35

Val Arg

Gln Ala

Pro Gly

Lys Gly

Leu Glu 45

Ser Val

Ile Trp

Tyr Asp

Gly Ser 55

Asn Arg

Tyr Tyr 60

Ala Asp

Gly Arg 15

Asn Tyr

Trp Val

Ser Val

Lys Gly 65

Arg Phe

Thr Ile

Ser Arg

Asp Thr

Ser Lys 75

Asn Thr

Leu Tyr 80

Leu Gln

Met Asn

Ser Leu 85

Arg Ala

Glu Asp 90

Thr Ala

Val Tyr

Tyr Cys 95

Ala Arg

Asp Pro

100

Pro Ile

Thr Gly

Thr Thr 105

Gly Gly

Asp Ala

110

Phe Asp

Ile Trp

Gly Gln 115

Gly Thr

Met Val

120

Thr Val

Ser Ser

Ala Ser 125

Thr Lys

Gly Pro

130

Ser Val

Phe Pro

Leu Ala 135

Pro Cys

Ser Arg

140

Ser Thr

Ser Glu

Ser Thr 145

Ala Ala

Leu Gly

150

Cys Leu

Val Lys

Asp Tyr 155

Phe Pro

Glu Pro

160

Val Thr

Val Ser

Trp Asn 165

Ser Gly

Ala Leu

170

Thr Ser

Gly Val

His Thr 175

Phe Pro

Ala Val

180

Leu Gln

Ser Ser

Gly Leu 185

Tyr Ser

Leu Ser

190

Ser Val

- 344 044746

Val Thr Val Pro Ser

195

Ser Ser Leu Gly Thr 200

Lys Thr Tyr Thr Cys

205

Val Asp His Lys Pro

210

Ser Asn Thr Lys Val

215

Asp Lys Arg Val Glu

220

Lys Tyr Gly Pro Pro 225

Cys Pro Pro Cys Pro 230

Ala Pro Gly Gly Gly 235

Pro Ser Val Phe Leu

245

Phe Pro Pro Lys Pro

250

Lys Asp Thr Leu Met

255

Ser Arg Thr Pro Glu

260

Val Thr Cys Val Val

265

Val Asp Val Ser Gln

270

Asp Pro Glu Val Gln

275

Phe Asn Trp Tyr Val

280

Asp Gly Val Glu Val

285

Asn Ala Lys Thr Lys

290

Pro Arg Glu Glu Gln

295

Phe Asn Ser Thr Tyr

300

Val Val Ser Val Leu 305

Thr Val Leu His Gln 310

Asp Trp Leu Asn Gly 315

Glu Tyr Lys Cys Lys

325

Val Ser Asn Lys Gly

330

Leu Pro Ser Ser Ile

335

Lys Thr Ile Ser Lys

340

Ala Lys Gly Gln Pro

345

Arg Glu Pro Gln Val

350

Thr Leu Pro Pro Ser

355

Gln Glu Glu Met Thr

360

Lys Asn Gln Val Ser

365

Thr Cys Leu Val Lys

370

Gly Phe Tyr Pro Ser

375

Asp Ile Ala Val Glu

380

Glu Ser Asn Gly Gln 385

Pro Glu Asn Asn Tyr 390

Lys Thr Thr Pro Pro 395

Leu Asp Ser Asp Gly

405

Ser Phe Phe Leu Tyr

410

Ser Arg Leu Thr Val

415

Lys Ser Arg Trp Gln

420

Glu Gly Asn Val Phe

425

Ser Cys Ser Val Met

430

Glu Ala Leu His Asn

435

His Tyr Thr Gln Lys 440

Ser Leu Ser Leu Ser

445

Asn

Ser

Gly 240

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

Leu

Trp

Val 400

Asp

His

Leu

- 345 044746

Gly Lys 450 <210> 355 <211> 1338 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>355 cagatcacct tgaaggagtc tggtcctacg ctggtgaaac ccacacagac cctcacgctg60 acctgcacct tctctgggtt ctcactcagc actaatgtag tgggtgtggg ctggatccgt120 cagcccccag gaaaggccct ggagtggct t gcactcattt attggaatga tgataagcgc180 tacagcccat ctctgaagag caggctcacc atcaccaagg acacctccaa aaaccaggtg240 gtccttacaa tgaccaacat ggaccctgtg gacacagcca catattactg tgcacacggc300 ccaactgggg actactttga ctactggggc cagggaaccc tggtcacc gt ctcctcagcc360 tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc420 acagccgccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggca c gaagacctac600 acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagagagt tgagtccaaa660 tatggtcccc catgcccacc gtgcccagca ccaggcggtg gcggaccatc agtcttcctg720 ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacg tgcgtg780 gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg840 gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag960 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag1020 ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag1080 gtcagcctga cctgcctggt caa aggcttc taccccagcg acatcgccgt ggagtgggag1140 agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc1200 tccttcttcc tctacagcag gctcaccgtg gacaagagca ggtggcagga ggggaatgtc1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gtccctctcc 1320 ctgtctctgg gtaaatga1338 <210>356 <211> 445

- 346 044746 <212> PROTEIN <213> Artificial <220>

<223> Synthetic <400> 356

Gln Ile Thr Leu Lys 1 5 sequence

Glu Ser Gly Pro Thr 10

Leu Val Lys Pro Thr

Thr Leu Thr Leu Thr

Cys Thr Phe Ser Gly 25

Phe Ser Leu Ser Thr

Val Val Gly Val Gly 35

Trp Ile Arg Gln Pro 40

Pro Gly Lys Ala Leu 45

Trp Leu Ala Leu Ile 50

Tyr Trp Asn Asp Asp 55

Lys Arg Tyr Ser Pro 60

Leu Lys Ser Arg Leu 65

Thr Ile Thr Lys Asp 70

Thr Ser Lys Asn Gln 75

Val Leu Thr Met Thr

Asn Met Asp Pro Val 90

Asp Thr Ala Thr Tyr 95

Cys Ala His Gly Pro

100

Thr Gly Asp Tyr Phe

105

Asp Tyr Trp Gly Gln

110

Thr Leu Val Thr Val

115

Ser Ser Ala Ser Thr

120

Lys Gly Pro Ser Val 125

Pro Leu Ala Pro Cys 130

Ser Arg Ser Thr Ser

135

Glu Ser Thr Ala Ala

140

Gly Cys Leu Val Lys 145

Asp Tyr Phe Pro Glu 150

Pro Val Thr Val Ser 155

Asn Ser Gly Ala Leu

165

Thr Ser Gly Val His

170

Thr Phe Pro Ala Val

175

Gln Ser Ser Gly Leu

180

Tyr Ser Leu Ser Ser

185

Val Val Thr Val Pro

190

Ser Ser Leu Gly Thr

195

Lys Thr Tyr Thr Cys 200

Asn Val Asp His Lys 205

Ser Asn Thr Lys Val

210

Asp Lys Arg Val Glu

215

Ser Lys Tyr Gly Pro

220

Gln

Asn

Glu

Ser

Val 80

Tyr

Gly

Phe

Leu

Trp 160

Leu

Ser

Pro

Pro

- 347 044746

Cys Pro Pro Cys Pro 225

Ala Pro Gly Gly Gly 230

Gly Pro Ser Val Phe 235

Phe Pro Pro Lys Pro

245

Lys Asp Thr Leu Met

250

Ile Ser Arg Thr Pro

255

Val Thr Cys Val Val

260

Val Asp Val Ser Gln

265

Glu Asp Pro Glu Val

270

Phe Asn Trp Tyr Val

275

Asp Gly Val Glu Val 280

His Asn Ala Lys Thr

285

Pro Arg Glu Glu Gln 290

Phe Asn Ser Thr Tyr

295

Arg Val Val Ser Val

300

Thr Val Leu His Gln 305

Asp Trp Leu Asn Gly 310

Lys Glu Tyr Lys Cys 315

Val Ser Asn Lys Gly

325

Leu Pro Ser Ser Ile

330

Glu Lys Thr Ile Ser

335

Ala Lys Gly Gln Pro

340

Arg Glu Pro Gln Val

345

Tyr Thr Leu Pro Pro

350

Gln Glu Glu Met Thr

355

Lys Asn Gln Val Ser 360

Leu Thr Cys Leu Val

365

Gly Phe Tyr Pro Ser

370

Asp Ile Ala Val Glu

375

Trp Glu Ser Asn Gly

380

Pro Glu Asn Asn Tyr 385

Lys Thr Thr Pro Pro 390

Val Leu Asp Ser Asp 395

Ser Phe Phe Leu Tyr

405

Ser Arg Leu Thr Val

410

Asp Lys Ser Arg Trp

415

Glu Gly Asn Val Phe

420

Ser Cys Ser Val Met

425

His Glu Ala Leu His

430

Leu 240

Glu

Gln

Lys

Leu

Lys 320

Lys

Ser

Lys

Gln

Gly 400

Gln

Asn

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser

440

Leu Gly Lys

445 <210> 357 <211> 1335 <212> DNA <213> Artificial sequence <220>

- 348 044746

<223> Synthetic <400> 357 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag tctctggggtt caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg gactggaatg ggtctcactt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtatatt actgtgcgag agaaggtgga 300 tacagctatg attacaacta ctggggccag ggaaccctgg tcaccgtctc ctcagcctcc 360 accaagggcc catcggtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 420 gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540 tactccctca gcagcgtggt gaccgtgccc tccagcagct tggggcacgaa gacctacacc 600 tgcaacgtag atcacaagcc cagcaacacc aaggtggac agagagttga gtccaaatat 660 ggtcccccat gccaccgtg cccagcacca ggcggtggcg gaccatcagt cttcctgttc 720 cccccaaaac ccaaggacac tctcatgatch tcccggaccc ctgaggtcac gtgcgtggtg 780 gtggacgtga gccaggaaga ccccgaggtc cagttcaact ggtacgtgga tggcgtggag 840 gtgcataatg ccaagacaaa gccgcggggag gagcagttca acagcacgta ccgtgtggtc 900 agcgtcctca ccgtcctgca ccaggactgg ctgaacggca aggagtacaa gtgcaaggtc 960 tccaacaaag gcctcccgtc ctccatcgag aaaaccatct ccaaagccaa agggcagccc 1020 cgagagccac aggtgtacac cctgccccca tccggagagg agatgaccaa gaaccaggtc 1080 agcctgacct gcctggtcaa aggcttctac cccagcgaca tcgccgtgga gtgggagagc 1140 aatggggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc 1200 ttcttcctct acagcaggct caccgtggac aagagcaggt ggcaggaggg gaatgtcttc 1260 tcatgctccg tgatgcatga ggctctgcac aaccactaca cacagaagtc cctctccctg 1320 tctctggggta aatga 1335

<210> 358 <211> 444 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 358

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

- 349 044746

Ser

Tyr

Ser

Gly 65

Gln

Arg

Leu

Leu

Cys 145

Ser

Ser

Ser

Asn

Pro 225

Pro

Thr

Leu Arg

Met Ser

Leu Ile 50

Arg Phe

Met Asn

Glu Gly

Val Thr

115

Ala Pro 130

Leu Val

Gly Ala

Ser Gly

Leu Gly

195

Thr Lys 210

Pro Cys

Pro Lys

Cys Val

Leu Ser 20

Trp Val

Tyr Ser

Thr Ile

Cys Ala

Arg Gln

Gly Gly

Ser Arg 70

Ser Leu

Gly Tyr 100

Val Ser

Cys Ser

Lys Asp

Leu Thr

165

Leu Tyr 180

Thr Lys

Val Asp

Pro Ala

Pro Lys

245

Val Val 260

Arg Ala

Ser Tyr

Ser Ala

Arg Ser

135

Tyr Phe 150

Ser Gly

Ser Leu

Thr Tyr

Lys Arg

215

Pro Gly 230

Asp Thr

Asp Val

Val Ser 25

Ala Pro 40

Ser Thr

His Asn

Glu Asp

Asp Tyr

105

Ser Thr 120

Thr Ser

Pro Glu

Val His

Ser Ser

185

Thr Cys 200

Val Glu

Gly Gly

Leu Met

Ser Gln

265

Gly Phe

Gly Lys

Phe Tyr

Ser Lys 75

Thr Ala 90

Asn Tyr

Lys Gly

Glu Ser

Pro Val

155

Thr Phe 170

Val Val

Asn Val

Ser Lys

Gly Pro

235

Ile Ser 250

Glu Asp

Thr Val

Gly Leu 45

Ala Asp 60

Asn Thr

Val Tyr

Trp Gly

Pro Ser

125

Thr Ala 140

Thr Val

Pro Ala

Thr Val

Asp His

205

Tyr Gly 220

Ser Val

Arg Thr

Pro Glu

Ser Ser 30

Glu Trp

Ser Val

Leu Tyr

Tyr Cys 95

Gln Gly 110

Val Phe

Ala Leu

Ser Trp

Val Leu

175

Pro Ser 190

Lys Pro

Pro Pro

Phe Leu

Pro Glu

255

Val Gln 270

Asn

Val

Lys

Leu 80

Ala

Thr

Pro

Gly

Asn 160

Gln

Ser

Ser

Cys

Phe 240

Val

Phe

- 350 044746

Asn Trp

Arg Glu

290

Val Leu 305

Ser Asn

Tyr Val 275

Glu Gln

His Gln

Lys Gly

Asp Gly

Phe Asn

Asp Trp

310

Leu Pro 325

Lys Gly

Glin Pro

340

Arg Glu

Glu Glu

Met Thr 355

Lys Asn

Phe Tyr

370

Pro Ser

Asp Ile

Val Glu

280

Ser Thr

295

Leu Asn

Ser Ser

Pro Gln

Gln Val

360

Ala Val 375

Val His

Tyr Arg

Gly Lys

Ile Glu

330

Val Tyr 345

Ser Leu

Glu Trp

Asn Ala

Val Val

300

Glu Tyr 315

Lys Thr

Thr Leu

Thr Cys

Glu Ser

380

Glu Asn 385

Asn Tyr

Lys Thr

390

Thr Pro

Pro Val

Leu Asp 395

Phe Phe

Leu Tyr

Ser Arg 405

Leu Thr

Val Asp

410

Lys Ser

Gly Asn

Val Phe

420

Ser Cys

Ser Val

Met His 425

Glu Ala

Tyr Thr

Gln Lys 435

Ser Leu

Ser Leu

440

Ser Leu

Gly Lys <210> 359 <211> 1332 <212> DNA <213> Artificial sequence

Synthetic

359 <220>

<223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg gactccgtga tggtggagtc cctctgggtt ggctggagtg agggccgatt tggaggaggc aaccgtcagt ggtctcagtt caccatctcc ttggtccagc agcaactaca atttatagcg agacacaatt

Lys Thr 285

Ser Val

Lys Cys

Ile Ser

Pro Pro

350

Leu Val 365

Asn Gly

Ser Asp

Arg Trp

Leu His

430 cggggggggtc tgaactgggt gtggtagtaa ccaagaacac

Lys Pro

Leu Thr

Lys Val

320

Lys Ala 335

Ser Gln

Lys Gly

Glin Pro

Gly Ser

400

Gln Glu 415

Asn His cctgagactc ccgccaggtt attctacgta gctgtatctt

120

180

240

- 351 044746

caaatgaaca gcctgagacc tgaggacacg gccgtgtatt actgtacgcg agacgcgcaa 300 tactacggta tggacgtctg gggccaaggg accacggtca ccgtctcctc agcctccacc 360 aagggcccat cggtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc 420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctacacctgc 600 aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt 660 ccccatgcc caccgtgccc agcaccaggc ggtggcggac catcagtctt cctgttcccc 720 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg 780 gacgtgagcc aggaagacc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 840 cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 900 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 960 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1020 gagccacagg tgtacaccct gcccccatcc caggagaga tgaccaagaa ccaggtcagc 1080 ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1140 gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1200 ttcctctaca gcaggctcac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1260 tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagtccct ctccctgtct 1320 ctgggtaaat ga 1332

<210> 360 <211> 443 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 360

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Leu Thr 25

Val Ser Ser Asn

Tyr Met Asn Trp 35

Val Arg Gln Val 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Ser Val Ile Tyr 50

Ser Gly Gly Ser 55

Lys Phe Tyr Val 60

Asp Ser Val Lys

- 352 044746

Gly Arg Phe Thr Ile 65

Ser Arg His Asn Ser 70

Lys Asn Thr Leu Tyr 75

Gln Met Asn Ser Leu

Arg Pro Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Asp Ala Gln Tyr

100

Tyr Gly Met Asp Val

105

Trp Gly Gln Gly Thr

110

Val Thr Val Ser Ser

115

Ala Ser Thr Lys Gly 120

Pro Ser Val Phe Pro

125

Ala Pro Cys Ser Arg 130

Ser Thr Ser Glu Ser

135

Thr Ala Ala Leu Gly 140

Leu Val Lys Asp Tyr 145

Phe Pro Glu Pro Val 150

Thr Val Ser Trp Asn 155

Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe

170

Pro Ala Val Leu Gln

175

Ser Gly Leu Tyr Ser

180

Leu Ser Ser Val Val

185

Thr Val Pro Ser Ser

190

Leu Gly Thr Lys Thr

195

Tyr Thr Cys Asn Val

200

Asp His Lys Pro Ser 205

Thr Lys Val Asp Lys

210

Arg Val Glu Ser Lys

215

Tyr Gly Pro Pro Cys

220

Pro Cys Pro Ala Pro 225

Gly Gly Gly Gly Pro 230

Ser Val Phe Leu Phe 235

Pro Lys Pro Lys Asp

245

Thr Leu Met Ile Ser

250

Arg Thr Pro Glu Val

255

Cys Val Val Val Asp

260

Val Ser Gln Glu Asp

265

Pro Glu Val Gln Phe

270

Trp Tyr Val Asp Gly

275

Val Glu Val His Asn

280

Ala Lys Thr Lys Pro

285

Glu Glu Gln Phe Asn

290

Ser Thr Tyr Arg Val

295

Val Ser Val Leu Thr

300

Leu His Gln Asp Trp

Leu Asn Gly Lys Glu

Tyr Lys Cys Lys Val

Leu 80

Thr

Thr

Leu

Cys

Ser 160

Ser

Ser

Asn

Pro

Pro 240

Thr

Asn

Arg

Val

Ser

- 353 044746

305

310

315

320

Asn Lys Gly Leu Pro Ser Ser Ile

325

Glu Lys Thr Ile Ser Lys Ala Lys

330 335

Gly Gln Pro Arg Glu Pro Gln Val 340

Tyr Thr Leu Pro Pro Ser Gln Glu

345 350

Glu Met Thr Lys Asn Gln Val Ser

355 360

Leu Thr Cys Leu Val Lys Gly Phe 365

Tyr Pro Ser Asp Ile Ala Val Glu

370 375

Trp Glu Ser Asn Gly Gln Pro Glu 380

Asn Asn Tyr Lys Thr Thr Pro Pro

385 390

Val Leu Asp Ser Asp Gly Ser Phe

395 400

Phe Leu Tyr Ser Arg Leu Thr Val 405

Asp Lys Ser Arg Trp Gln Glu Gly

410 415

Asn Val Phe Ser Cys Ser Val Met 420

His Glu Ala Leu His Asn His Tyr

425 430

Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435440 <210>361 <211>1335 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 361

gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctgggat caccgtcagt agcaattaca tgacctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca acctgagagc tgaggacacg gccgtgtatt actgtgtgag agatctagag 300 gttcggggcg gtatggacgt ctggggccaa gggaccacgg tcaccgtctc ctcagcctcc 360 accaagggcc catcggtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 420 gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540 tactccctca gcagcgtggt gaccgtgccc tccagcagct tggggcacgaa gacctacacc 600

- 354 044746 tgcaacgtag ggtcccccat cccccaaaac gtggacgtga gtgcataatg agcgtcctca tccaacaaag cgagagccac agcctgacct aatgggcagc ttcttcctct tcatgctccg tctctgggta atcacaagcc gcccaccgtg ccaaggacac gccaggaaga cca agacaaa ccgtcctgca gcctcccgtc aggtgtacac gcctggtcaa cggagaacaa acagcaggct tgatgcatga aatga cagcaacacc cccagcacca tctcatgatc ccccgaggtc gccgcgggag ccaggactgg ctccatcgag cctgccccca aggcttctac ctacaagacc caccgtggac ggctct gcac aaggtggaca ggcggtggcg tcccggaccc cagttcaact gagcagttca ctgaacggca aaaaccatct tcccaggagg cccagcgaca acgcctcccg aagagcaggt aaccactaca agagagttga gaccatcagt ctgaggtcac ggtacgtgga acagcacgta aggagtacaa ccaaagccaa agatgaccaa tcgccgtgga tgctggactc ggcaggaggg cacagaagtc gtccaaatat cttcctgttc gtgcgtggtg tgg cgtggag ccgtgtggtc gtgcaaggtc agggcagccc gaaccaggtc gtggggagagc cgacggctcc gaatgtcttc cctctccctg

660

720

780

840

900

960

1020

1080

1140

1200

1260

1320

1335 <210> 362 <211> 444 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 362

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Ile Thr Val Ser Ser Asn 25 30

Tyr Met Thr Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Ser Gly Gly Ser

55

Thr Phe Tyr Ala Asp Ser Val Lys 60

Gly Arg Phe Thr Ile Ser Arg His 65 70

Asn Ser Lys Asn Thr Leu Tyr Leu

80

Gln Met Asn Asn Leu Arg Ala Glu 85

Asp Thr Ala Val Tyr Tyr Cys Val

95

Arg Asp Leu Glu Val Arg Gly Gly

Met Asp Val Trp Gly Gln Gly Thr

- 355 044746

100

105

110

Thr Val Thr Val Ser

115

Ser Ala Ser Thr Lys

120

Gly Pro Ser Val Phe

125

Leu Ala Pro Cys Ser 130

Arg Ser Thr Ser Glu

135

Ser Thr Ala Ala Leu

140

Cys Leu Val Lys Asp 145

Tyr Phe Pro Glu Pro 150

Val Thr Val Ser Trp 155

Ser Gly Ala Leu Thr

165

Ser Gly Val His Thr

170

Phe Pro Ala Val Leu

175

Ser Ser Gly Leu Tyr

180

Ser Leu Ser Ser Val

185

Val Thr Val Pro Ser

190

Ser Leu Gly Thr Lys

195

Thr Tyr Thr Cys Asn 200

Val Asp His Lys Pro

205

Asn Thr Lys Val Asp 210

Lys Arg Val Glu Ser

215

Lys Tyr Gly Pro

220

Pro Pro Cys Pro Ala 225

Pro Gly Gly Gly Gly 230

Pro Ser Val Phe Leu 235

Pro Pro Lys Pro Lys

245

Asp Thr Leu Met Ile

250

Ser Arg Thr Pro Glu

255

Thr Cys Val Val Val

260

Asp Val Ser Gln Glu

265

Asp Pro Glu Val Gln

270

Asn Trp Tyr Val Asp

275

Gly Val Glu Val His

280

Asn Ala Lys Thr Lys

285

Arg Glu Glu Gln Phe 290

Asn Ser Thr Tyr Arg

295

Val Val Ser Val Leu

300

Val Leu His Gln Asp 305

Trp Leu Asn Gly Lys 310

Glu Tyr Lys Cys Lys 315

Ser Asn Lys Gly Leu

325

Pro Ser Ser Ile Glu

330

Lys Thr Ile Ser Lys

335

Lys Gly Gln Pro Arg

340

Glu Pro Gln Val Tyr

345

Thr Leu Pro Pro Ser

350

Pro

Gly

Asn 160

Gln

Ser

Ser

Cys

Phe 240

Val

Phe

Pro

Thr

Val 320

Ala

Gln

- 356 044746

Glu Glu Met Thr Lys Asn Gln Val

355 360

Ser Leu Thr Cys Leu Val Lys Gly

365

Phe Tyr Pro Ser Asp Ile Ala Val

370 375

Glu Trp Glu Ser Asn Gly Gln Pro 380

Glu Asn Asn Tyr Lys Thr Thr Pro

385 390

Pro Val Leu Asp Ser Asp Gly Ser

395 400

Phe Phe Leu Tyr Ser Arg Leu Thr 405

Val Asp Lys Ser Arg Trp Gln Glu

410 415

Gly Asn Val Phe Ser Cys Ser Val 420

Met His Glu Ala Leu His Asn His

425 430

Tyr Thr Gln Lys Ser Leu Ser Leu

435440

Ser Leu Gly Lys <210>363 <211>1347 <212> DNA <213> Artificial Sequence <220>

<223> Synthetic

<400> 363 gaagtgcagc tggtggagtc tgggggaggc ttggttcagc ctggcaggtc cctgagactc 60 tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120 ccagggaagg gcctggagtg ggtctcaggt gttagttgga atagtggtac catagactat 180 gcggactctg tgaagggccg attcaccatt attagagaca acgctaagaa ctccctgtat 240 ctgcaaatga acagtctgag agctgaagac acggccttgt attackgttc aaaagatatg 300 gggaggctag actactactc cggtttggac gtctggggcc aagggaccac ggtcaccgtc 360 tcctcagcct ccaccaaggg cccacggtc ttccccctgg cgccctgctc caggagcacc 420 tccgagagca cagccgccct gggctgcctg gtcaaggact acttccccga accggtgacg 480 gtgtcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 540 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttggggcacg 600 aagactaca cctgcaacgt agatcacaag cccagcaaca ccaaggtgga caagagagtt 660 gagtccaaat atggtccccc atgcccaccg tgcccagcac caggcggtgg cggaccatca 720 gtcttcctgt tccccccaaa acccaaggac actctcatga tctcccggac ccctgaggtc 780 acgtgcgtgg tggtggacgt gagccaggaa gaccccgagg tccagttcaa ctggtacgtg 840 gatggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagtt caacagcacg 900

- 357 044746

taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaacgg caaggagtac 960 aagtgcaagg tctccaacaa aggcctcccg tcctccatcg agaaaaccat ctccaaagcc 1020 aaagggcagc cccgagagcc acaggtgtac accctgcccc catccagga ggagatgacc 1080 aagaaccagg tcagcctgac ctgcctggtc aaaggcttct accccagcga catcgccgtg 1140 gagtggggaga gcaatggggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1200 tccgacggct ccttcttcct ctacagg ctcaccgtgg acaagagcag gtggcaggag 1260 gggaatgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacacagaag 1320 tccctctccc tgtctctggg taaatga 1347

<210> 364 <211> 448 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>364

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Arg 1 5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asp Asp Tyr 20 2530

Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Gly Val Ser Trp Asn Ser Gly Thr Ile Asp Tyr Ala Asp Ser Val 50 5560

Lys Gly Arg Phe Thr Ile Ile Arg Asp Asn Ala Lys Asn Ser Leu Tyr 65 70 7580

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys 85 9095

Ser Lys Asp Met Gly Arg Leu Asp Tyr Tyr Ser Gly Leu Asp Val Trp

100 105110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

115 120125

Ser Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr

130 135140

- 358 044746

Ala 145

Val

Ala

Val

His

Gly 225

Val

Thr

Glu

Lys

Ser 305

Lys

Ile

Pro

Leu

Asn 385

Ala Leu Gly

Ser Trp Asn

Val Leu Gln

180

Pro Ser Ser

195

Lys Pro Ser 210

Pro Pro Cys

Phe Leu Phe

Pro Glu Val

260

Val Gln Phe

275

Thr Lys Pro 290

Val Leu Thr

Cys Lys Val

Ser Lys Ala

340

Pro Ser Gln

355

Val Lys Gly 370

Gly Gln Pro

Cys Leu Val

150

Lys Asp Tyr

Phe Pro Glu 155

Pro Val Thr

160

Ser Gly Ala 165

Ser Ser Gly

Ser Leu Gly

Asn Thr Lys

215

Pro Pro Cys

230

Pro Pro Lys 245

Thr Cys Val

Asn Trp Tyr

Arg Glu Glu

295

Val Leu His

310

Ser Asn Lys 325

Lys Gly Gln

Glu Glu Met

Phe Tyr Pro

375

Glu Asn Asn

390

Leu Thr Ser

170

Leu Tyr Ser

185

Thr Lys Thr 200

Val Asp Lys

Pro Ala Pro

Pro Lys Asp

250

Val Val Asp

265

Val Asp Gly 280

Gln Phe Asn

Gln Asp Trp

Gly Leu Pro

330

Pro Arg Glu

345

Thr Lys Asn 360

Ser Asp Ile

Tyr Lys Thr

Gly Val His

Thr Phe Pro

175

Leu Ser Ser

Tyr Thr Cys

205

Arg Val Glu

220

Gly Gly Gly 235

Thr Leu Met

Val Ser Gln

Val Glu Val

285

Ser Thr Tyr

300

Leu Asn Gly 315

Ser Ser Ile

Pro Gln Val

Gln Val Ser

365

Ala Val Glu

380

Thr Pro Pro 395

Val Val Thr 190

Asn Val Asp

Ser Lys Tyr

Gly Pro Ser

240

Ile Ser Arg

255

Glu Asp Pro 270

His Asn Ala

Arg Val Val

Lys Glu Tyr

320

Glu Lys Thr

335

Tyr Thr Leu 350

Leu Thr Cys

Trp Glu Ser

Val Leu Asp

400

- 359 044746

Ser Asp Gly Ser Phe Phe Leu Tyr 405

Arg Trp Gln Glu Gly Asn Val Phe 420

Leu His Asn His Tyr Thr Gln Lys 435 440

Ser Arg 410 Leu Thr Val Asp Lys 415 Ser Ser 425 Cys Ser Val Met His 430 Glu Ala Ser Leu Ser Leu Ser 445 Leu Gly Lys

365

357

DNA

Artificial

Synthetic

365 <210>

<211>

<212> <213>

<220>

<223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca atggcagcag sequence tggtggagtc cctctggaat ggctggagtg agggcagatt gcctgagagt cggggtataa tgggggaggc caccgtcagt ggtctcactt caccatctcc cgaggacacg ttactggggc ttggt ccagc agcaactaca atttatagtg agagacaatt gctgtgtatt cagggaaccc ctggggggtc tgagctgggt gtggtagcac ccaagaacac actgtgcgag tggtcaccgt actgagactc ccgccaggct atactacgca gctgtatctt agatcacggt ctcctca

120

180

240

300

357 <210> 366 <211> 119 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>366

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ile Thr Val Ser Ser Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Leu Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

- 360 044746

Gln Met Asn

Ser

Leu Arg Val Glu Asp Thr Ala 85 90

Val Tyr Tyr Cys Ala

Arg Asp His Gly Met Ala Ala Ala Gly Tyr Asn Tyr Trp Gly Gln Gly

100 105110

Thr Leu Val Thr Val Ser Ser

115 <210>367 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>367 ggaatcaccg tcagtagcaa ctac <210>368 <211>21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>368 atttatagtg gtggtagcac a <210>369 <211>39 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>369 gcgagagatc acggtatggc agcagcgggg tataattac <210>370 <211>13 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 370

Ala Arg Asp His Gly Met Ala Ala Ala Gly Tyr Asn Tyr 1 5 10

- 361 044746 <210> 371 <211> 321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>371 gacatccaga tgacccagtc tccatcctcc ctgtctgcgt ctgtaggaga cagagtcacc60 atcacttgcc aggcgagtca ggacattaac aaatatttaa attggtatca gcagaaacca120 gggaaagccc ctaagctcct gatctacgat gcatccaatt tgga aacagg ggtcccatca180 aggttcagtg gaagtggatc tgggacagat tttactttca ccatcaacag cctgcagcct240 gaagattttg caacatattt ctgtcaacag tatgataatc tccctccagc gttcggccaa300 gggaccaagg tggaaatcaa a321 <210>372 < 211>107 < 212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 372

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

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

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

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

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Asn Ser Leu Gln Pro

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

Ala Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100

105 <210>

<211>

373

- 362 044746 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>373 caggacatta acaaatat <210>374 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>374 caacagtatg ataatctccc tccagcg <210>375 <211>9 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>375

Gln Gln Tyr Asp Asn Leu Pro Pro Ala 15 <210>376 <211>1350 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 376 gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca atggcagcag tccaccaagg acagcggccc aactcaggcg tggtggagtc cctctggaat ggctggagtg agggcagatt gcctgagagt cggggtataa gcccatcggt tggg ctgcct ccctgaccag tgggggaggc caccgtcagt ggtctcactt caccatctcc cgaggacacg ttactggggc cttccccctg ggtcaaggac cggcgtgcac ttggtccagc agcaactaca atttatagtg agagacaatt gctgtgtatt cagggaaccc gcaccctcct tacttccccg accttccc gg ctggggggtc tgagctgggt gtggtagcac ccaagaacac actgtgcgag tggtcaccgt ccaagagcac aaccggtgac ctgtcctaca actgagactc ccgccaggct atactacgca gctgtatctt agatcacggt ctcctcagcc ctctgggggc ggtgtcgtgg gtcctcagga

120

180

240

300

360

420

480

540

- 363 044746

ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac ccagacctac 600 atctgcaacg tgaatcacaa gccagcaac accaaggtgg acaagaaagt tgagcccaaa 660 tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720 tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780 gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840 gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900 acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaagggag 960 tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020 gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080 accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140 gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200 gactccgacg gctccttctt ccctacagc aagctcaccg tggacaagag caggtggcag 1260 caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320 aagtccctct ccctgtctcc gggtaaatga 1350

<210> 377 <211> 449 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>377

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Ile Thr Val Ser Ser Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Leu Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Ser Leu Arg Val Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

- 364 044746

Arg

Thr

Pro

Gly 145

Asn

Gln

Ser

Ser

Thr 225

Ser

Arg

Pro

Ala

Val 305

Tyr

Thr

Asp His Gly

100

Met Ala Ala

Ala Gly Tyr

105

Asn Tyr Trp

Gly Gln Gly 110

Leu Val Thr

115

Leu Ala Pro 130

Cys Leu Val

Ser Gly Ala

Ser Ser Gly

180

Ser Leu Gly

195

Asn Thr Lys 210

His Thr Cys

Val Phe Leu

Thr Pro Glu

260

Glu Val Lys

275

Lys Thr Lys 290

Ser Val Leu

Lys Cys Lys

Ile Ser Lys

340

Val Ser Ser

Ala Ser Thr 120

Lys Gly Pro

125

Ser Val Phe

Ser Ser Lys

135

Ser Thr Ser

Gly Gly Thr

140

Ala Ala Leu

Lys Asp Tyr

150

Leu Thr Ser 165

Leu Tyr Ser

Thr Gln Thr

Val Asp Lys

215

Pro Pro Cys

230

Phe Pro Pro 245

Val Thr Cys

Phe Asn Trp

Pro Arg Glu

295

Thr Val Leu

310

Val Ser Asn 325

Ala Lys Gly

Phe Pro Glu

Pro Val Thr 155

Val Ser Trp

160

Gly Val His

170

Leu Ser Ser

185

Tyr Ile Cys 200

Lys Val Glu

Pro Ala Pro

Lys Pro Lys

250

Val Val Val

265

Tyr Val Asp 280

Glu Gln Tyr

His Gln Asp

Lys Ala Leu

330

Gln Pro Arg

345

Thr Phe Pro

Ala Val Leu

175

Val Val Thr

Val Pro Ser 190

Asn Val Asn

205

Pro Lys Ser

220

Glu Leu Leu 235

Asp Thr Leu

Asp Val Ser

Gly Val Glu

285

Asn Ser Thr

300

Trp Leu Asn 315

Pro Ala Pro

Glu Pro Gln

His Lys Pro

Cys Asp Lys

Gly Gly Pro

240

Met Ile Ser

255

His Glu Asp 270

Val His Asn

Tyr Arg Val

Gly Lys Glu

320

Ile Glu Lys

335

Val Tyr Thr 350

- 365 044746

Leu Pro Pro Ser Arg Asp Glu Leu

355 360

Thr Lys Asn Gln Val Ser Leu Thr 365

Cys Leu Val Lys Gly Phe Tyr Pro

370 375

Ser Asp Ile Ala Val Glu Trp Glu 380

Ser Asn Gly Gln Pro Glu Asn Asn

385 390

Tyr Lys Thr Thr Pro Pro Val Leu

395 400

Asp Ser Asp Gly Ser Phe Phe Leu

405

Tyr Ser Lys Leu Thr Val Asp Lys

410 415

Ser Arg Trp Gln Gln Gly Asn Val 420

Phe Ser Cys Ser Val Met His Glu

425 430

Ala Leu His Asn His Tyr Thr Gln

435 440

Lys Ser Leu Ser Leu Ser Pro Gly

445

Lys

<210> 378 <211> 645 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 378 gacatccaga tgacccagtc tccatcctcc ctgtctgcgt ctgtaggaga cagagtcacc 60 atcacttgcc aggcgagtca ggacattaac aaatatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccatcaacag cctgcagcct 240 gaagatttg caacatattt ctgtcaacag tatgataatc tccctccagc gttcggccaa 300 gggaccaagg tggaaatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcaggggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 645

<210> 379 <211> 214

- 366 044746 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>379

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Asn Lys Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Asn Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Phe Cys Gln Gln Tyr Asp Asn Leu Pro Pro 85 9095

Ala Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala

100 105110

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

115 120125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155160

Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser

165 170175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys

210

- 367 044746 <210> 380 <211> 345 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 380

gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagagtc 60 tcctgtgcag cctctggatt caccgtcagt aggaactaca tgagttgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc cgaggacacg gctatatatt actgtgcgag atacattcct 300 aggttcgacc cctggggcca gggaaccctg gtcaccgtct cctca 345

<210> 381 <211> 115 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>381

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Val Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Arg Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile Tyr Tyr Cys Ala 85 9095

Arg Tyr Ile Pro Arg Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr

100 105110

Val Ser Ser

115

- 368 044746 <210> 382 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>382 ggattcaccg tcagtaggaa ctac24 <210>383 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>383

Gly Phe Thr Val Ser Arg Asn Tyr < 210 > 384 < 211 > 27 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic <400>384 gcgagataca ttcctaggtt cgacccc27 <210>385 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>385

Ala Arg Tyr Ile Pro Arg Phe Asp Pro < 210 > 386 < 211 > 321 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic <400> 386

- 369 044746

gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc aggcgagtca ggacattagc aactatttaa attggtttca gcagaaacca 120 ggggagagccc ctaagctcct catctacgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaagatattg caacatatta ctgtcaacag tatgataatc tcccgatcac cttcggccaa 300 gggacacgac tggagattaa a 321

<210> 387 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>387

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 2530

Leu Asn Trp Phe Gln Gln Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 4045

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Pro Ile 85 9095

Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys

100105 <210>388 <211>18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 388 caggacatta gcaactat

- 370 044746 <210> 389 <211> 6 <212> PROTEIN <213> Artificial sequence <220>

<223>Synthetic <400>389

Gln Asp Ile Ser Asn Tyr <210>390 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>390 caacagtatg ataatctccc gatcacc <210>391 <211>1338 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 391 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagagtc 60 tcctgtgcag cctctggatt caccgtcagt aggaactaca tgagttgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc cgaggacacg gctatatatt actgtgcgag atacattcct 300 aggttcgacc cctggggcca gggaaccctg gtcaccgtct cctcagcctc caccaagggc 360 ccatcggtct tccccctggc accctcctcc aagagcacct ctggggggcac agcggccctg 420 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540 agcagcgtgg tgaccgtgcc ctccagcagc ttggggcaccc agacctacat ctgcaacgtg 600 aatcacaagc ccagcaacac caaggtggac aagaaagttg agcccaaatc ttgtgacaaa 660 actcacacat gccaccgtg cccagcacct gaactcctgg ggggaccgtc agtcttcctc 720 ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 780 gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 840

- 371 044746

gaggtgcata atgccaagac aaagccgcgg gagggagt acaacagcac gtaccgtgtg 900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaatg gcaagggagta caagtgcaag 960 gtctccaaca aagccctccc agcccccatc gagaaaacca tctccaaagc caaagggcag 1020 ccccgagaac cacaggtgta caccctgccc ccaccccgggg atgagctgac caagaaccag 1080 gtcagcctga cctgcctggt caaaggcttc tatcccagcg acatcgccgt ggagtggggag 1140 agcaatggggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200 tccttcttcc tctacagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gtccctctcc 1320 ctgtctccgg gtaaatga 1338

<210> 392 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>392

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 1015

Ser Leu Arg Val Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Arg Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Ile Tyr Tyr Cys Ala 85 9095

Arg Tyr Ile Pro Arg Phe Asp Pro Trp Gly Gln Gly Thr Leu Val Thr

100 105110

Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro

115 120125

Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val

130 135140

- 372 044746

Lys 145

Leu

Leu

Thr

Val

Pro 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg

Gly

Pro

Asp Tyr Phe

Thr Ser Gly

Tyr Ser Leu

180

Gln Thr Tyr

195

Asp Lys Lys 210

Pro Cys Pro

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Lys Gly Gln

340

Asp Glu Leu

355

Phe Tyr Pro 370

Glu Asn Asn

Pro Glu Pro

150

Val His Thr 165

Ser Ser Val

Ile Cys Asn

Val Glu Pro

215

Ala Pro Glu

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Gln Tyr Asn

295

Gln Asp Trp

310

Ala Leu Pro 325

Pro Arg Glu

Thr Lys Asn

Ser Asp Ile

375

Tyr Lys Thr

Val Thr Val

Phe Pro Ala

170

Val Thr Val

185

Val Asn His 200

Lys Ser Cys

Leu Leu Gly

Thr Leu Met

250

Val Ser His

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ala Pro Ile

330

Pro Gln Val

345

Gln Val Ser 360

Ala Val Glu

Thr Pro Pro

Ser Trp Asn 155

Val Leu Gln

Pro Ser Ser

Lys Pro Ser

205

Asp Lys Thr 220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Tyr Thr Leu

Leu Thr Cys

365

Trp Glu Ser

380

Val Leu Asp

Ser Gly Ala

160

Ser Ser Gly

175

Ser Leu Gly 190

Asn Thr Lys

His Thr Cys

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

Pro Pro Ser 350

Leu Val Lys

Asn Gly Gln

Ser Asp Gly

- 373 044746

385 390 395 400

Ser Phe Phe Leu

Tyr Ser Lys Leu 405

Thr Val Asp Lys 410

Ser Arg Trp Gln

415

Gln Gly Asn Val

420

Phe Ser Cys Ser

Val Met His Glu 425

Ala Leu His Asn

430

His Tyr Thr Gln

435

Lys Ser Leu Ser

440

Leu Ser Pro Gly

Lys 445

<210> 393 <211> 645 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 393 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc aggcgagtca ggacattagc aactatttaa attggtttca gcagaaacca 120 ggggagagccc ctaagctcct catctacgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaagatattg caacatatta ctgtcaacag tatgataatc tcccgatcac cttcggccaa 300 gggacacgac tggagattaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcaggggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 645

<210> 394 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 394

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Gln Ala

Ser Gln Asp Ile Ser Asn Tyr

25

- 374 044746

Leu Asn

Tyr Asp 50

Ser Gly 65

Glu Asp

Trp Phe 35

Ala Ser

Ser Gly

Ile Ala

Gln Gln

Lys Pro 40

Gly Arg

Ala Pro

Thr Phe

Gly Gln

100

Pro Ser

Val Phe

115

Thr Ala

130

Ser Val

Asn Leu

Thr Asp 70

Thr Tyr 85

Gly Thr

Ile Phe

Val Cys

Glu Thr 55

Gly Val

Pro Ser

Phe Thr

Phe Thr

Ile Ser 75

Tyr Cys

Gln Gln

Tyr Asp

Lys Leu 45

Arg Phe

Ser Leu

Asn Leu

Leu Ile

Ser Gly

Glin Pro

Pro Ile 95

Arg Leu

Pro Pro

120

Leu Leu 135

Glu Ile 105

Lys Arg

Thr Val

110

Ala Ala

Ser Asp

Glu Gln

Leu Lys 125

Ser Gly

Asn Asn

Phe Tyr

140

Pro Arg

Glu Ala

Lys Val 145

Gln Trp

Lys Val

150

Asp Asn

Ala Leu

Gln Ser 155

Gly Asn

Ser Gln

160

Glu Ser

Val Thr

Glu Gln 165

Asp Ser

Lys Asp

170

Ser Thr

Tyr Ser

Leu Ser 175

Ser Thr

Leu Thr

180

Leu Ser

Lys Ala

Asp Tyr 185

Glu Lys

His Lys

190

Val Tyr

Ala Cys

Glu Val 195

Thr His

Gln Gly

200

Leu Ser

Ser Pro

Val Thr 205

Lys Ser

Phe Asn Arg

210

Gly Glu Cys <210> 395 <211> 351 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 395 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc tcctgtgcag cctccggact caccgtcagt agcaactaca tgagctgggt ccgccaggct

120

- 375 044746

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agatcttatc 300 aaatacggta tggacgtctg gggccaaggg accacggtca ccgtctcctc a 351

<210> 396 <211> 117 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>396

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Leu Thr Val Ser Ser Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

Arg Asp Leu Ile Lys Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105110

Val Thr Val Ser Ser

115 <210>397 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 397 ggactcaccg tcagtagcaa ctac

- 376 044746 <210> 398 <211> 33 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>398 gcgagagatc ttatcaaata cggtatggac gtc <210>399 <211>11 <212> PROTEIN <213> Artificial sequence <220>

<223>Synthetic <400>399

Ala Arg Asp Leu Ile Lys Tyr Gly Met Asp Val

510 < 210> 400 < 211> 321 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400> 400

gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaagatattg caacatatta ctgtcaacag tatgataatc tccctcccca tttcggccct 300 gggaccaaag tggatatcaa a 321

<210> 401 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 401

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr

- 377 044746

Leu Asn Trp Tyr Gln Gln Lys Pro

40

Gly Lys Ala Pro Lys Leu Leu Ile 45

Tyr Asp Ala Ser Asn Leu Glu Thr

55

Gly Val Pro Ser Arg Phe Ser Gly 60

Ser Gly Ser Gly Thr Asp Phe Thr 65 70

Phe Thr Ile Ser Ser Leu Gln Pro

80

Glu Asp Ile Ala Thr Tyr Tyr Cys 85

Gln Gln Tyr Asp Asn Leu Pro Pro

95

His Phe Gly Pro Gly Thr Lys Val

100

Asp Ile Lys 105 <210> 402 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>402 caacagtatg ataatctccc tccccat <210>403 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>403

Gln Gln Tyr Asp Asn Leu Pro Pro His <210>404 <211>1344 <212> DNA <213> Artificial sequence

Synthetic

404 <220>

<223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg tggtggagtc cctccggact ggctggagtg tgggggaggc caccgtcagt ggtctcagtt ttggtccagc agcaactaca atttatagcg ctggggggtc tgagctgggt gtggtagcac cctgagactc ccgccaggct attctacgca

120

180

- 378 044746

gactccgtga aggggccgatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agatcttatc 300 aaatacggta tggacgtctg gggccaaggg accacggtca ccgtctcctc agcctccacc 360 aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc 600 aacgtgaatc acaagcccag caacaccaag gtggacaaga aagttgagcc caaatcttgt 660 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 720 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 780 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 840 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 900 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 960 tgcaaggtct ccaacaaagc cctcccagcc ccatcgaga aaaccatctc caaagccaaa 1020 gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 1080 aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1140 tggggagagca atggggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1200 gacggctcct tcttcctcta cagcaagctc accgtggac agagcaggtg gcagcagggg 1260 aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagtcc 1320 ctctccctgt ctccgggtaa atga 1344

<210> 405 <211> 447 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 405

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Leu Thr 25

Val Ser Ser Asn

Tyr Met Ser Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

- 379 044746

Ser

Gly 65

Gln

Arg

Val

Ala

Leu 145

Gly

Ser

Leu

Thr

Thr 225

Phe

Pro

Val

Thr

Val Ile Tyr 50

Arg Phe Thr

Met Asn Ser

Asp Leu Ile

100

Thr Val Ser

115

Pro Ser Ser 130

Val Lys Asp

Ala Leu Thr

Gly Leu Tyr

180

Gly Thr Gln

195

Lys Val Asp 210

Cys Pro Pro

Leu Phe Pro

Glu Val Thr

260

Lys Phe Asn

275

Lys Pro Arg 290

Ser Gly Gly 55

Ser Thr Phe

Tyr Ala Asp 60

Ser Val Lys

Ile Ser Arg 70

Leu Arg Ala 85

Lys Tyr Gly

Ser Ala Ser

Lys Ser Thr

135

Tyr Phe Pro

150

Ser Gly Val 165

Ser Leu Ser

Thr Tyr Ile

Lys Lys Val

215

Cys Pro Ala

230

Pro Lys Pro 245

Cys Val Val

Trp Tyr Val

Glu Glu Gln

295

Asp Asn Ser

Lys Asn Thr 75

Leu Tyr Leu

Glu Asp Thr

Met Asp Val

105

Thr Lys Gly 120

Ser Gly Gly

Glu Pro Val

His Thr Phe

170

Ser Val Val

185

Cys Asn Val 200

Glu Pro Lys

Pro Glu Leu

Lys Asp Thr

250

Val Asp Val

265

Asp Gly Val 280

Tyr Asn Ser

Ala Val Tyr

Tyr Cys Ala 95

Trp Gly Gln

Gly Thr Thr 110

Pro Ser Val

125

Phe Pro Leu

Thr Ala Ala

140

Thr Val Ser 155

Pro Ala Val

Thr Val Pro

Asn His Lys

205

Ser Cys Asp

220

Leu Gly Gly 235

Leu Met Ile

Ser His Glu

Glu Val His

285

Thr Tyr Arg

300

Leu Gly Cys

Trp Asn Ser

160

Leu Gln Ser

175

Ser Ser Ser 190

Pro Ser Asn

Lys Thr His

Pro Ser Val

240

Ser Arg Thr

255

Asp Pro Glu 270

Asn Ala Lys

Val Val Ser

- 380 044746

Val Leu 305

Cys Lys

Ser Lys

Pro Ser

Thr Val

Val Ser

Ala Lys

340

Arg Asp 355

Leu His

310

Asn Lys 325

Gly Gln

Glu Leu

Gln Asp

Ala Leu

Pro Arg

Thr Lys

360

Trp Leu

Pro Ala

330

Glu Pro 345

Asn Gln

Val Lys

370

Gly Phe

Tyr Pro

Ser Asp 375

Ile Ala

Gly Gln 385

Pro Glu

Asn Asn

390

Tyr Lys

Thr Thr

Asp Gly

Ser Phe

Phe Leu 405

Tyr Ser

Lys Leu

410

Trp Gln

Gln Gly

420

Asn Val

Phe Ser

Cys Ser 425

His Asn

His Tyr 435

Thr Gln

Lys Ser

440

Leu Ser

Asn Gly 315

Pro Ile

Gln Val

Val Ser

Val Glu 380

Pro Pro 395

Thr Val

Val Met

Leu Ser

Lys Glu

Glu Lys

Tyr Thr

350

Leu Thr 365

Trp Glu

Val Leu

Asp Lys

His Glu

430

Pro Gly 445

Tyr Lys

320

Thr Ile 335

Leu Pro

Cys Leu

Ser Asn

Asp Ser

400

Ser Arg 415

Ala Leu

Lys <210>

<211>

<212>

<213>

406

645

DNA

Artificial sequence <220>

<223> Synthetic <400> 406 gacatccaga atcacttgcc gggaaagccc aggttcagtg gaagatattg gggaccaaag tctgatgagc cccagagagg tgacccagtc aggcgagtca ctaagctcct gaagtggatc caacatatta tggatatcaa agttgaaatc ccaaagtaca tccat cctcc ggacattagc gatctacgat tgggacagat ctgtcaacag acgaactgtg tggaactgcc gtggaaggtg ctgtctgcat aactatttaa gcatccaatt tttactttca tatgataatc gctgcaccat tctgttgtgt gataacgccc ctgtaggaga attggtatca tggaaacagg ccatcagcag t ccctcccca ctgtcttcat gcctgctgaa tccaatcggg cagagtcacc gcagaaacca ggtcccatca cctgcagcct tttcggccct cttcccgcca taacttctat taactcccag

120

180

240

300

360

420

480

- 381 044746 gagagtgtca ctgagcaaag ctgagctcgc cagagcagga cagactacga ccgtcacaaa cagcaaggac gaaacacaaa gagcttcaac agcacctaca gtctacgcct aggggagagt gcctcagcag gcgaagtcac gttag caccctgacg ccatcagggc

540

600

645 <210> 407 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 407

Asp Ile 1

Gln Met

Thr Gln 5

Ser Pro

Ser Ser

Leu Ser

Ala Ser

Asp Arg

Val Thr

Ile Thr

Cys Gln

Ala Ser 25

Gln Asp

Ile Ser

Leu Asn

Trp Tyr 35

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

Lys Leu 45

Tyr Asp 50

Ala Ser

Asn Leu

Glu Thr 55

Gly Val

Pro Ser

Arg Phe

Val Gly 15

Asn Tyr

Leu Ile

Ser Gly

Ser Gly 65

Ser Gly

Thr Asp 70

Phe Thr

Phe Thr

Ile Ser 75

Ser Leu

Glin Pro

Glu Asp

Ile Ala

Thr Tyr 85

Tyr Cys

Gln Gln

Tyr Asp

Asn Leu

Pro Pro 95

His Phe

Gly Pro

100

Gly Thr

Lys Val

Asp Ile 105

Lys Arg

Thr Val

110

Ala Ala

Pro Ser

Val Phe 115

Ile Phe

Pro Pro

120

Ser Asp

Glu Gln

Leu Lys 125

Ser Gly

Thr Ala

130

Ser Val

Val Cys

Leu Leu 135

Asn Asn

Phe Tyr

140

Pro Arg

Glu Ala

Lys Val 145

Gln Trp

Lys Val

150

Asp Asn

Ala Leu

Gln Ser 155

Gly Asn

Ser Gln

160

Glu Ser

Val Thr

Glu Gln 165

Asp Ser

Lys Asp

170

Ser Thr

Tyr Ser

Leu Ser 175

Ser Thr

Leu Thr

180

Leu Ser

Lys Ala

Asp Tyr 185

Glu Lys

His Lys

190

Val Tyr

- 382 044746

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195

200

205

Phe Asn Arg Gly Glu Cys

210 <210> 408 <211> 351 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>408 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc60 tcctgtgcag cctctggggt caccgtcagt agcaactata tgagctgggt ccgccaggct120 ccagggaagg ggctggagtg ggtctcagt t atttatagcg gtggtagtac attctacgca180 gactccgtga agggccgatt taccatctcc agagacaact ccaagaacac gctgtttctt240 caaatgaaca gcctgagaat tgaggacacg gccgtgtatt attgtgcgag agatttaggt300 ccttacggta tggacgtctg gggccaaggg accac ggtca ccgtctcctc a351 <210>409 <211 >117 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 409

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe Leu

Gln Met Asn Ser Leu Arg Ile Glu Asp Thr Ala Val Tyr Tyr Cys Ala

- 383 044746

Arg Asp Leu Gly Pro Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115 <210> 410 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 410 ggggtcaccg tcagtagcaa ctat <210> 411 <211> 8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 411

Gly Val Thr Val Ser Ser Asn Tyr

5 <210> 412 <211> 21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 412 atttatagcg gtggtagtac a <210> 413 <211> 33 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 413 gcgagagatt taggtcctta cggtatggac gtc <210> 414 <211> 11

- 384 044746 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>414

Ala Arg Asp Leu Gly Pro Tyr Gly Met Asp Val

510 <210>415 <211>324 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>415 gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc60 atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca120 gggaaagccc ctaagctcct gatctatgct gcatccactt tg caaagtgg ggtcccatca180 aggttcagcg gcagtggatc tgggacacaa ttcattctca caatcagcag cctgcagcct240 gaagattttg caacttatta ctgtcaacag cttaatagtt accccggatt cactttcggc300 cctgggacca aagtggatat caaa324 <210>416 <211>108 < 212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>416

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

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Tyr 20 2530

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Gln Phe Ile Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

- 385 044746

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Gly 85 9095

Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100

105 <210>417 <211>30 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>417 caacagctta atagttaccc cggattcact <210>418 <211>10 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>418

Gln Gln Leu Asn Ser Tyr Pro Gly Phe Thr

510 <210>419 <211>1344 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 419 gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca ccttacggta aagggcccat gccctgggct ggcgccctga tccctcagca tggtggagtc cctctggggt ggctggagtg agggccgatt gcctgagaat tggacgtctg cgg tcttccc gcctggtcaa ccagcggcgt gcgtggtgac tggaggaggc caccgtcagt ggtctcagtt taccatctcc tgaggacacg gggccaaggg cctggcaccc ggactacttc gcacaccttc cgtgccctcc ttggtccagc agcaactata atttatagcg agagacaact gccgtgtatt acc acggtca tcctccaaga cccgaaccgg ccggctgtcc agcagcttgg ctggggggtc tgagctgggt gtggtagtac ccaagaacac attgtgcgag ccgtctcctc gcacctctgg tgacggtgtc tacagtcctc gcacccagac cctgagactc ccgccaggct attctacgca gctgtttctt agatttaggt agcctccacc gggcacagcg gtggaactca aggactctac ctacatctgc

120

180

240

300

360

420

480

540

600

- 386 044746

aacgtgaatc acaagcccag caacaccaag gtggacaaga aagttgagcc caaatcttgt 660 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 720 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 780 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 840 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 900 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 960 tgcaaggtct ccaacaaagc cctcccagcc ccatcgaga aaaccatctc caaagccaaa 1020 gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 1080 aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1140 tggggagagca atggggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1200 gacggctcct tcttcctcta cagcaagctc accgtggac agagcaggtg gcagcagggg 1260 aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagtcc 1320 ctctccctgt ctccgggtaa atga 1344

<210> 420 <211> 447 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>420

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe Leu 65 70 7580

Gln Met Asn Ser Leu Arg Ile Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

Arg Asp Leu Gly Pro Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

- 387 044746

100

105

110

Val Thr Val Ser Ser

115

Ala Ser Thr Lys Gly 120

Pro Ser Val Phe Pro

125

Ala Pro Ser Ser Lys 130

Ser Thr Ser Gly Gly

135

Thr Ala Ala Leu Gly 140

Leu Val Lys Asp Tyr 145

Phe Pro Glu Pro Val 150

Thr Val Ser Trp Asn 155

Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe

170

Pro Ala Val Leu Gln

175

Ser Gly Leu Tyr Ser

180

Leu Ser Ser Val Val

185

Thr Val Pro Ser Ser

190

Leu Gly Thr Gln Thr 195

Tyr Ile Cys Asn Val 200

Asn His Lys Pro Ser 205

Thr Lys Val Asp Lys

210

Lys Val Glu Pro Lys

215

Ser Cys Asp Lys Thr

220

Thr Cys Pro Pro Cys 225

Pro Ala Pro Glu Leu 230

Leu Gly Gly Pro Ser 235

Phe Leu Phe Pro Pro

245

Lys Pro Lys Asp Thr

250

Leu Met Ile Ser Arg

255

Pro Glu Val Thr Cys

260

Val Val Val Asp Val

265

Ser His Glu Asp Pro

270

Val Lys Phe Asn Trp

275

Tyr Val Asp Gly Val

280

Glu Val His Asn Ala

285

Thr Lys Pro Arg Glu

290

Glu Gln Tyr Asn Ser

295

Thr Tyr Arg Val Val

300

Val Leu Thr Val Leu 305

His Gln Asp Trp Leu 310

Asn Gly Lys Glu Tyr 315

Cys Lys Val Ser Asn

325

Lys Ala Leu Pro Ala

330

Pro Ile Glu Lys Thr

335

Ser Lys Ala Lys Gly

340

Gln Pro Arg Glu Pro

345

Gln Val Tyr Thr Leu

350

Leu

Cys

Ser 160

Ser

Ser

Asn

His

Val 240

Thr

Glu

Lys

Ser

Lys 320

Ile

Pro

- 388 044746

Pro Ser Arg Asp Glu Leu Thr Lys

355 360

Asn Gln Val Ser Leu

365

Val Lys Gly Phe Tyr Pro Ser Asp

370 375

Ile Ala Val Glu Trp

380

Gly Gln Pro Glu Asn Asn Tyr Lys

385 390

Thr Thr Pro Pro Val

395

Asp Gly Ser Phe Phe Leu Tyr Ser 405

Lys Leu Thr Val Asp

410

Trp Gln Gln Gly Asn Val Phe Ser 420

Cys Ser Val Met His 425

His Asn His Tyr Thr Gln Lys Ser

435 440

Leu Ser Leu Ser Pro

445

Thr Cys Leu

Glu Ser Asn

Leu Asp Ser 400

Lys Ser Arg 415

Glu Ala Leu 430

Gly Lys <210> 421 <211> 648 <212> DNA <213> Artificial Sequence <220>

<223> Synthetic

<400> 421 gacatccagt tgaccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120 gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180 aggttcagcg gcagtggatc tgggacacaa ttcattctca caatcagcag cctgcagcct 240 gaagatttg caacttatta ctgtcaacag cttaatagtt accccggatt cactttcggc 300 cctggacca aagtggatat caaacgaact gtggctgcac catctgtctt catcttcccg 360 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420 tatccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 648

<210> 422 <211> 215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic

- 389 044746 <400> 422

Asp Ile Gln 1

Asp Arg Val

Leu Thr Gln

Ser Pro Ser

Phe Leu Ser 10

Ala Ser Val

Leu Ala Trp

Tyr Ala Ala 50

Ser Gly Ser 65

Glu Asp Phe

Phe Thr Phe

Ala Pro Ser

115

Gly Thr Ala

130

Ala Lys Val 145

Gln Glu Ser

Ser Ser Thr

Tyr Ala Cys

195

Ser Phe Asn

210

Thr Ile Thr 20

Cys Arg Ala

Ser Gln Gly

Ile Ser Ser

Tyr Gln Gln

Lys Pro Gly 40

Lys Ala Pro

Lys Leu Leu 45

Ser Thr Leu

Gln Ser Gly 55

Val Pro Ser

Arg Phe Ser

Gly Thr Gln

Phe Ile Leu

Thr Ile Ser

Ser Leu Gln

Ala Thr Tyr 85

Gly Pro Gly 100

Val Phe Ile

Ser Val Val

Gln Trp Lys

150

Val Thr Glu

165

Leu Thr Leu 180

Glu Val Thr

Arg Gly Glu

Tyr Cys Gln

Gln Leu Asn 90

Ser Tyr Pro

Thr Lys Val

105

Phe Pro Pro

120

Cys Leu Leu 135

Val Asp Asn

Gln Asp Ser

Ser Lys Ala

185

His Gln Gly 200

Cys 215

Asp Ile Lys

Arg Thr Val

110

Ser Asp Glu

Gln Leu Lys 125

Asn Asn Phe

140

Ala Leu Gln

155

Lys Asp Ser 170

Asp Tyr Glu

Leu Ser Ser <210> 423 <211> 1338 <212> DNA <213> Artificial sequence

Tyr Pro Arg

Ser Gly Asn

Thr Tyr Ser

175

Lys His Lys 190

Pro Val Thr 205

Gly

Tyr

Ile

Gly

Pro 80

Gly

Ala

Ser

Glu

Ser 160

Leu

Val

Lys

- 390 044746 <220>

<223> Synthetic <400>423 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc actgagactc60 tcctgtgcag cctctggaat caccgtcagt agcaactaca tgagctgggt ccgccaggct120 ccagggaagg ggctggagtg ggtctcactt at ttatagtg gtggtagcac atactacgca180 gactccgtga agggcagatt caccatctcc agagacaatt ccaagaacac gctgtatctt240 caaatgaaca gcctgagagt cgaggacacg gctgtgtatt actgtgcgag agatcacggt300 atggcagcag cggggtataa ttactggggc cagggaaccc t ggtcaccgt ctcctcagcc360 tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc420 acagccgccc tgggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttgggca c gaagacctac600 acctgcaacg tagatcacaa gcccagcaac accaaggtgg acaagagagt tgagtccaaa660 tatggtcccc catgcccacc gtgcccagca ccaggcggtg gcggaccatc agtcttcctg720 ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacg tgcgtg780 gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg840 gaggtgcata atgccaagac aaagccgcgg gaggagcagt tcaacagcac gtaccgtgtg900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaaggagta caagtgcaag960 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag1020 ccccgagagc cacaggtgta caccctgccc ccatcccagg aggagatgac caagaaccag1080 gtcagcctga cctgcctggt caa aggcttc taccccagcg acatcgccgt ggagtgggag1140 agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc1200 tccttcttcc tctacagcag gctcaccgtg gacaagagca ggtggcagga ggggaatgtc1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gtccctctcc 1320 ctgtctctgg gtaaatga1338 <210>424 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 424

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

- 391 044746

Ser

Tyr

Ser

Gly 65

Gln

Arg

Thr

Pro

Gly 145

Asn

Gln

Ser

Ser

Cys 225

Phe

Leu Arg Leu 20

Ser Cys Ala

Ala Ser Gly 25

Ile Thr Val

Ser Ser Asn 30

Met Ser Trp 35

Val Arg Gln

Ala Pro Gly 40

Lys Gly Leu 45

Glu Trp Val

Leu Ile Tyr 50

Ser Gly Gly 55

Ser Thr Tyr

Tyr Ala Asp 60

Ser Val Lys

Arg Phe Thr

Met Asn Ser

Asp His Gly

100

Leu Val Thr

115

Leu Ala Pro 130

Cys Leu Val

Ser Gly Ala

Ser Ser Gly

180

Ser Leu Gly

195

Asn Thr Lys 210

Pro Pro Cys

Pro Pro Lys

Ile Ser Arg 70

Leu Arg Val 85

Met Ala Ala

Val Ser Ser

Cys Ser Arg

135

Lys Asp Tyr

150

Leu Thr Ser 165

Leu Tyr Ser

Thr Lys Thr

Val Asp Lys

215

Pro Ala Pro

230

Pro Lys Asp 245

Asp Asn Ser

Glu Asp Thr

Ala Gly Tyr

105

Ala Ser Thr 120

Ser Thr Ser

Phe Pro Glu

Gly Val His

170

Leu Ser Ser

185

Tyr Thr Cys 200

Arg Val Glu

Gly Gly Gly

Thr Leu Met

250

Lys Asn Thr 75

Leu Tyr Leu

Ala Val Tyr

Asn Tyr Trp

Lys Gly Pro

125

Glu Ser Thr

140

Pro Val Thr 155

Thr Phe Pro

Val Val Thr

Asn Val Asp

205

Ser Lys Tyr

220

Gly Pro Ser 235

Ile Ser Arg

Tyr Cys Ala 95

Gly Gln Gly 110

Ser Val Phe

Ala Ala Leu

Val Ser Trp

160

Ala Val Leu

175

Val Pro Ser 190

His Lys Pro

Gly Pro Pro

Val Phe Leu

240

Thr Pro Glu

255

- 392 044746

Val Thr

Cys Val

260

Val Val

Asp Val

Phe Asn

Trp Tyr 275

Val Asp

Gly Val

280

Pro Arg

290

Glu Glu

Gln Phe

Asn Ser 295

Thr Val 305

Leu His

Gln Asp

310

Trp Leu

Ser Gln 265

Glu Val

Thr Tyr

Asn Gly

Glu Asp

His Asn

Arg Val

300

Lys Glu 315

Val Ser

Asn Lys

Gly Leu 325

Pro Ser

Ser Ile

330

Glu Lys

Ala Lys

Gly Gln

340

Pro Arg

Glu Pro

Gln Val 345

Tyr Thr

Gln Glu

Glu Met 355

Thr Lys

Asn Gln

360

Val Ser

Leu Thr

Pro Glu

270

Ala Lys 285

Val Ser

Tyr Lys

Thr Ile

Leu Pro

350

Cys Leu 365

Val Gln

Thr Lys

Val Leu

Cys Lys

320

Ser Lys 335

Pro Ser

Val Lys

Gly Phe

370

Tyr Pro

Ser Asp

Ile Ala

375

Val Glu

Trp Glu

380

Ser Asn

Gly Gln

Pro Glu 385

Asn Asn

Tyr Lys

390

Thr Thr

Pro Pro

Val Leu 395

Asp Ser

Asp Gly

400

Ser Phe

Phe Leu

Tyr Ser 405

Arg Leu

Thr Val

410

Asp Lys

Ser Arg

Trp Gln 415

Glu Gly

Asn Val

420

Phe Ser

Cys Ser

ValMet 425

His Glu

Ala Leu

430

His Asn

His Tyr

Thr Gln 435

Lys Ser

Leu Ser

440

Leu Ser

Leu Gly

Lys

445 <210> 425 <211> 1326 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 425 gaggtgcagc tggtggagtc tgggggaggc tcctgtgcag cctctggatt caccgtcagt ccagggaagg ggctggagtg ggtctcagtt ttggtccagc ctggggggtc cctgagagtc aggaactaca tgagttgggt ccgccaggct att tatagcg gtggtagcac attctacgca

120

180

- 393 044746

gactccgtga aggggatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc cgaggacacg gctatatatt actgtgcgag atacattcct 300 aggttcgacc cctggggcca gggaaccctg gtcaccgtct cctcagcctc caccaagggc 360 ccatcggtct tccccctggc gccctgctcc aggagcacct ccgagagcac agccgccctg 420 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540 agcagcgtgg tgaccgtgcc ctccagcagc ttggggcacga agacctacac ctgcaacgta 600 gatcacaagc ccagcaacac caaggtggac aagagagttg agtccaaata tggtccccca 660 tgccaccgt gccagcacc aggcggtggc ggaccatcag tcttcctgtt ccccccaaaa 720 cccaaggaca ctctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg 780 agccaggaag accccgaggt ccagttcaac tggtacgtgg atggcgtgga ggtgcataat 840 gccaagacaa agccgcggga ggagcagttc aacagcacgt accgtgtggt cagcgtcctc 900 accgtcctgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa 960 ggcctcccgt cctccatcga gaaaaccatc tccaaagcca aagggcagcc ccgagagcca 1020 caggtgtaca ccctgccccc atcccaggag gagatgacca agaaccaggt cagcctgacc 1080 tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agggggagag caatggggcag 1140 ccggagaaca actacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc 1200 tacagcaggc tcaccgtgga caagagcagg tggcaggagg ggaatgtctt ctcatgctcc 1260 gtgatgcatg aggctctgca caaccactac acacagaagt ccctctccct gtctctggggt 1320

aaatga

1326 <210> 426 <211> 441 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>426

Glu Val Gln Leu Val Glu Ser Gly Gly 15

Ser Leu Arg Val Ser Cys Ala Ala Ser 2025

Tyr Met Ser Trp Val Arg Gln Ala Pro

3540

Gly Leu Val Gln Pro Gly Gly

15

Gly Phe Thr Val Ser Arg Asn 30

Gly Lys Gly Leu Glu Trp Val 45

- 394 044746

Ser

Gly 65

Gln

Arg

Val

Cys

Lys 145

Leu

Leu

Thr

Val

Pro 225

Pro

Val

Val

Gln

Val Ile Tyr 50

Arg Phe Thr

Met Asn Ser

Tyr Ile Pro

100

Ser Ser Ala

115

Ser Arg Ser 130

Asp Tyr Phe

Thr Ser Gly

Tyr Ser Leu

180

Lys Thr Tyr

195

Asp Lys Arg 210

Ala Pro Gly

Lys Asp Thr

Val Asp Val

260

Asp Gly Val

275

Phe Asn Ser 290

Ser Gly Gly 55

Ser Thr Phe

Tyr Ala Asp 60

Ser Val Lys

Ile Ser Arg 70

Leu Arg Ala 85

Arg Phe Asp

Ser Thr Lys

Thr Ser Glu

135

Pro Glu Pro

150

Val His Thr 165

Ser Ser Val

Thr Cys Asn

Val Glu Ser

215

Gly Gly Gly

230

Leu Met Ile 245

Ser Gln Glu

Glu Val His

Thr Tyr Arg

295

Asp Asn Ser

Lys Asn Thr 75

Leu Tyr Leu

Glu Asp Thr

Pro Trp Gly

105

Gly Pro Ser 120

Ser Thr Ala

Val Thr Val

Phe Pro Ala

170

Val Thr Val

185

Val Asp His 200

Lys Tyr Gly

Pro Ser Val

Ser Arg Thr

250

Asp Pro Glu

265

Asn Ala Lys 280

Val Val Ser

Ala Ile Tyr

Tyr Cys Ala 95

Gln Gly Thr

Leu Val Thr 110

Val Phe Pro

125

Ala Leu Gly

140

Ser Trp Asn 155

Val Leu Gln

Pro Ser Ser

Lys Pro Ser

205

Pro Pro Cys

220

Phe Leu Phe 235

Pro Glu Val

Val Gln Phe

Thr Lys Pro

285

Val Leu Thr

300

Leu Ala Pro

Cys Leu Val

Ser Gly Ala

160

Ser Ser Gly

175

Ser Leu Gly 190

Asn Thr Lys

Pro Pro Cys

Pro Pro Lys

240

Thr Cys Val

255

Asn Trp Tyr 270

Arg Glu Glu

Val Leu His

- 395 044746

Gln Asp 305

Gly Leu

Pro Arg

Thr Lys

Ser Asp 370

Tyr Lys 385

Tyr Ser

Phe Ser

Lys Ser

Trp Leu

Pro Ser

Glu Pro

340

Asn Gln 355

Ile Ala

Thr Thr

Arg Leu

Cys Ser

420

Leu Ser 435

Asn Gly

310

Ser Ile

325

Gln Val

Val Ser

Val Glu

Pro Pro

390

Thr Val 405

Val Met

Leu Ser

Lys Glu

Glu Lys

Tyr Thr

Leu Thr

360

Trp Glu 375

Val Leu

Asp Lys

His Glu

Leu Gly

440

Tyr Lys

Thr Ile

330

Leu Pro 345

Cys Leu

Ser Asn

Asp Ser

Ser Arg

410

Ala Leu 425

Lys

427

1332

DNA

Artificial

Synthetic

427 <210>

<211>

<212> <213>

<220> <223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca aaatacggta aagggcccat gccctgggct ggcgccctga sequence tggtggagtc cctccggact ggctggagtg agggccgatt gcctgagagc tggacgtctg cggtcttccc gcctggtcaa ccagcggcgt t gggggaggc caccgtcagt ggtctcagtt caccatctcc tgaggacacg gggccaaggg cctggcgccc ggactacttc gcacaccttc

Cys Lys 315

Ser Lys

Pro Ser

Val Lys

Gly Gln 380

Asp Gly 395

Trp Gln

His Asn ttggtccagc agcaactaca atttatagcg agagacaatt gctgtgtatt accacggtca tgctccagga cccgaaccgg ccggctgtcc

Val Ser

Ala Lys

Gln Glu

350

Gly Phe 365

Pro Glu

Ser Phe

Glu Gly

His Tyr

430 ctggggggtc tgagctgggt gtggtagcac ccaagaacac actgtgcgag ccgtctcctc gcacctccga tgacggtgtc tacagtcctc

Asn Lys

320

Gly Gln 335

GluMet

Tyr Pro

Asn Asn

Phe Leu

400

Asn Val 415

Thr Gln cctgagactc ccgccaggct attctacgca gctgtatctt agatcttatc agcctccacc gagcacagcc gtggaactca aggactctac

120

180

240

300

360

420

480

540

- 396 044746

tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctacacctgc 600 aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt 660 ccccatgcc caccgtgccc agcaccaggc ggtggcggac catcagtctt cctgttcccc 720 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg 780 gacgtgagcc aggaagacc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 840 cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 900 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 960 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1020 gagccacagg tgtacaccct gcccccatcc caggagaga tgaccaagaa ccaggtcagc 1080 ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1140 gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1200 ttcctctaca gcaggctcac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1260 tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagtccct ctccctgtct 1320

ctgggtaaat ga

1332 <210> 428 <211> 443 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 428

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Leu Thr Val Ser Ser Asn 25 30

Tyr Met Ser Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Ser Gly Gly Ser

55

Thr Phe Tyr Ala Asp Ser Val Lys 60

Gly Arg Phe Thr Ile Ser Arg Asp 65 70

Asn Ser Lys Asn Thr Leu Tyr Leu

80

Gln Met Asn Ser Leu Arg Ala Glu 85

Asp Thr Ala Val Tyr Tyr Cys Ala

95

- 397 044746

Arg

Val

Ala

Leu 145

Gly

Ser

Leu

Thr

Pro 225

Pro

Cys

Trp

Glu

Leu 305

Asn

Gly

Asp Leu

Thr Val

115

Pro Cys 130

Val Lys

Ala Leu

Gly Leu

Gly Thr

195

Lys Val 210

Cys Pro

Lys Pro

Val Val

Tyr Val

275

Glu Gln

290

His Gln

Lys Gly

Glin Pro

Ile Lys 100

Ser Ser

Ser Arg

Asp Tyr

Thr Ser

165

Tyr Ser 180

Lys Thr

Asp Lys

Ala Pro

Lys Asp

245

Val Asp 260

Asp Gly

Phe Asn

Asp Trp

Leu Pro

325

Arg Glu 340

Tyr Gly

Ala Ser

Ser Thr

135

Phe Pro 150

Gly Val

Leu Ser

Tyr Thr

Arg Val

215

Gly Gly 230

Thr Leu

Val Ser

Val Glu

Ser Thr

295

Leu Asn 310

Ser Ser

Pro Gln

Met Asp 105

Thr Lys 120

Ser Glu

Glu Pro

His Thr

Val Trp

Gly Pro

Ser Thr

Val Thr

155

Phe Pro 170

Gly Gln

Ser Val

125

Ala Ala

140

Val Ser

Ala Val

Ser Val

185

Cys Asn 200

Glu Ser

Gly Gly

Met Ile

Gln Glu

265

Val His 280

Tyr Arg

Gly Lys

Ile Glu

Val Tyr

345

Val Thr

Val Asp

Lys Tyr

Pro Ser

235

Ser Arg 250

Asp Pro

Asn Ala

Val Val

Glu Tyr

315

Lys Thr 330

Thr Leu

Val Pro

His Lys

205

Gly Pro 220

Val Phe

Thr Pro

Glu Val

Lys Thr

285

Ser Val

300

Lys Cys

Ile Ser

Pro Pro

Gly Thr 110

Phe Pro

Leu Gly

Trp Asn

Leu Gln

175

Ser Ser 190

Pro Ser

Pro Cys

Leu Phe

Glu Val

255

Gln Phe

270

Lys Pro

Leu Thr

Lys Val

Lys Ala

335

Ser Gln

350

Thr

Leu

Cys

Ser 160

Ser

Ser

Asn

Pro

Pro 240

Thr

Asn

Arg

Val

Ser 320

Lys

Glu

- 398 044746

Glu Met Thr Lys Asn Gln Val Ser

355 360

Leu Thr Cys Leu Val Lys Gly Phe 365

Tyr Pro Ser Asp Ile Ala Val Glu

370 375

Trp Glu Ser Asn Gly Gln Pro Glu 380

Asn Asn Tyr Lys Thr Thr Pro Pro

385 390

Val Leu Asp Ser Asp Gly Ser Phe

395 400

Phe Leu Tyr Ser Arg Leu Thr Val 405

Asp Lys Ser Arg Trp Gln Glu Gly

410 415

Asn Val Phe Ser Cys Ser Val Met 420

His Glu Ala Leu His Asn His Tyr

425 430

Thr Gln Lys Ser Leu Ser Leu Ser

435 440

Leu Gly Lys <210> 429 <211> 1332 <212> DNA <213> Artificial Sequence <220>

<223> Synthetic <400> 429 gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca ccttacggta aagggcccat gccctgggct ggcgccctga tccctcagca aacgtagatc cccccatgcc ccaaaaccca gacgtgagcc tggtggagtc cctctggggt ggct ggagtg agggccgatt gcctgagaat tggacgtctg cggtcttccc gcctggtcaa ccagcggcgt gcgtggtgac acaagcccag caccgtgccc aggacactct aggaagaccc tggaggaggc caccgtcagt ggtctcagtt taccatctcc tgaggacacg gggccaaggg cctggcgccc gg actacttc gcacaccttc cgtgccctcc caacaccaag agcaccaggc catgatctcc cgaggtccag ttggtccagc agcaactata atttatagcg agagacaact gccgtgtatt accacggtca tgctccagga cccgaaccgg ccggctgtcc agcagcttgg gtggacaaga ggtggcggac cggacccctg ttcaactggt ctggggggtc tgagctgggt gtggtagtac ccaagaacac attgtgcgag ccg tctcctc gcacctccga tgacggtgtc tacagtcctc gcacgaagac gagttgagtc catcagtctt aggtcacgtg acgtggatgg cctgagactc ccgccaggct attctacgca gctgtttctt agatttaggt agcctccacc gagcacagcc gtggaactca aggactctac ctacacctgc ca aatatggt cctgttcccc cgtggtggtg cgtggaggtg

120

180

240

300

360

420

480

540

600

660

720

780

840

- 399 044746

cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 900 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 960 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1020 gagccacagg tgtacaccct gcccccatcc caggagaga tgaccaagaa ccaggtcagc 1080 ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1140 gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1200 ttcctctaca gcaggctcac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1260 tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagtccct ctccctgtct 1320 ctgggtaaat ga 1332

<210> 430 <211> 443 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>430

Glu Val Gln Leu Val

5

Ser Leu Arg Leu Ser 20

Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1015

Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn 2530

Tyr Met

Ser Trp Val Arg Gln Ala Pro Gly Lys 3540

Gly Leu Glu Trp Val 45

Ser Val Ile

Gly Arg Phe 65

Gln Met Asn

Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp 5560

Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr 7075

Ser Leu Arg Ile Glu Asp Thr Ala Val Tyr 8590

Ser Val Lys

Leu Phe Leu

Tyr Cys Ala 95

Arg Asp Leu Gly Pro Tyr Gly Met Asp Val

100105

Trp

Gly Gln Gly Thr Thr

110

Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu

115 120125

Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys

130 135140

- 400 044746

Leu Val Lys Asp Tyr 145

Phe Pro Glu Pro Val 150

Thr Val Ser Trp Asn 155

Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe

170

Pro Ala Val Leu Gln

175

Ser Gly Leu Tyr Ser

180

Leu Ser Ser Val Val

185

Thr Val Pro Ser Ser

190

Leu Gly Thr Lys Thr

195

Tyr Thr Cys Asn Val

200

Asp His Lys Pro Ser 205

Thr Lys Val Asp Lys

210

Arg Val Glu Ser Lys

215

Tyr Gly Pro Pro Cys

220

Pro Cys Pro Ala Pro 225

Gly Gly Gly Gly Pro 230

Ser Val Phe Leu Phe 235

Pro Lys Pro Lys Asp

245

Thr Leu Met Ile Ser

250

Arg Thr Pro Glu Val

255

Cys Val Val Val Asp

260

Val Ser Gln Glu Asp

265

Pro Glu Val Gln Phe

270

Trp Tyr Val Asp Gly

275

Val Glu Val His Asn

280

Ala Lys Thr Lys Pro

285

Glu Glu Gln Phe Asn

290

Ser Thr Tyr Arg Val

295

Val Ser Val Leu Thr

300

Leu His Gln Asp Trp 305

Leu Asn Gly Lys Glu 310

Tyr Lys Cys Lys Val 315

Asn Lys Gly Leu Pro

325

Ser Ser Ile Glu Lys

330

Thr Ile Ser Lys Ala

335

Gly Gln Pro Arg Glu

340

Pro Gln Val Tyr Thr

345

Leu Pro Pro Ser Gln

350

Glu Met Thr Lys Asn

355

Gln Val Ser Leu Thr

360

Cys Leu Val Lys Gly

365

Tyr Pro Ser Asp Ile

370

Ala Val Glu Trp Glu

375

Ser Asn Gly Gln Pro

380

Asn Asn Tyr Lys Thr

Thr Pro Pro Val Leu

Asp Ser Asp Gly Ser

Ser 160

Ser

Ser

Asn

Pro

Pro 240

Thr

Asn

Arg

Val

Ser 320

Lys

Glu

Phe

Glu

Phe

- 401 044746

385

Phe Leu Tyr Ser

Asn Val Phe Ser 420

Thr Gln Lys Ser 435

390

Arg Leu Thr Val 405

Cys Ser Val Met

Leu Ser Leu Ser

440

395

Asp Lys Ser Arg 410

His Glu Ala Leu 425

Leu Gly Lys

400

Trp Gln Glu Gly

415

His Asn His Tyr 430 <210>431 <211>354 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 431

caggtgcagc tgcaggagtc ggggccagga ctggtgaagc cttcggagac cctgtccctc 60 acctgcactg tctctggtgg ctccacatcaat aattactact ggatctggat ccggcagccc 120 ccagggaagg gactggagtg gattggggtat atctatcaca gtgggagcac caactacaac 180 ccctccctca agagtcgagt caccatatca gtagacacgt ccaagaacca attctccctg 240 aaggtgagct ctgtgaccgc tgcggacacg gccgtgtatt actgtgcgaa tatggttcgg 300 ggagtttatg aagatgacta ctggggccag ggaaccctgg tcaccgtctc ctca 354

<210>432 <211>118 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 432

Gln Val Gln Leu 1

Gln Glu Ser Gly 5

Pro Gly Leu Val 10

Lys Pro Ser Glu 15

Thr Leu Ser Leu

Thr Cys Thr Val

Ser Gly Gly Ser 25

Ile Asn Asn Tyr 30

Tyr Trp Ile Trp 35

Ile Arg Gln Pro 40

Pro Gly Lys Gly

Leu Glu Trp Ile 45

Gly Tyr Ile Tyr 50

His Ser Gly Ser 55

Thr Asn Tyr Asn 60

Pro Ser Leu Lys

- 402 044746

Ser 65 Arg Val Thr Ile Ser 70 Val Asp Thr Ser Lys 75 Asn Gln Phe Ser Leu 80 Lys Val Ser Ser Val 85 Thr Ala Ala Asp Thr 90 Ala Val Tyr Tyr Cys 95 Ala Asn Met Val Arg 100 Gly Val Tyr Glu Asp 105 Asp Tyr Trp Gly Gln 110 Gly Thr Leu Val Thr 115 Val Ser Ser

<210> 433 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>433 ggtggctcca tcaataatta ctac <210>434 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>434

Gly Gly Ser Ile Asn Asn Tyr Tyr <210>435 <211>21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>435 atctatcaca gtgggagcac c <210>436 <211>7 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 436

- 403 044746

Ile Tyr His Ser Gly Ser Thr <210> 437 <211> 36 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>437 gcgaatatgg ttcggggagt ttatgaagat gactac36 <210>438 <211>12 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>438

Ala Asn Met Val Arg Gly Val Tyr Glu Asp Asp Tyr

510 < 210 > 439 < 211 > 321 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic <400>439 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc60 atcacttgcc gggcaagtca gagcattagc aactatttaa attggtatca gcagaaacca120 gggaaagccc ctaagctcct gatctttgct gcctccagtt t gcgaagtgg ggtcccatca180 aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaccct240 gaagattttg caacttacta ctgtcaacag aattacaata cccccctcac tttcggccct300 gggaccaaag tggatatcaa a321 < 210 > 440 < 211>107 < 212> PROTEIN <213> Artificial sequence <220>

<223>

Synthetic <400>

440

- 404 044746

Asp Ile Gln Met Thr Gln Ser Pro 1 5

Ser Ser Leu Ser Ala Ser Val Gly

15

Asp Arg Val Thr Ile Thr Cys Arg 20

Ala Ser Gln Ser Ile Ser Asn Tyr 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro

40

Gly Lys Ala Pro Lys Leu Leu Ile 45

Phe Ala Ala Ser Ser Leu Arg Ser

55

Gly Val Pro Ser Arg Phe Ser Gly 60

Ser Gly Ser Gly Thr Asp Phe Thr 65 70

Leu Thr Ile Ser Ser Leu His Pro

80

Glu Asp Phe Ala Thr Tyr Tyr Cys 85

Gln Gln Asn Tyr Asn Thr Pro Leu

95

Thr Phe Gly Pro Gly Thr Lys Val

100

Asp Ile Lys 105 <210> 441 <211> 18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>441 cagagcatta gcaactat <210>442 <211>6 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>442

Gln Ser Ile Ser Asn Tyr <210>443 <211>9 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 443

- 405 044746 gctgcctcc 9 <210> 444 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>444 caacagaatt acaatacccc cctcact27 <210>445 <211>9 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>445

Gln Gln Asn Tyr Asn Thr Pro Leu Thr 15 <210>446 <211>1347 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 446

caggtgcagc tgcaggagtc ggggccagga ctggtgaagc cttcggagac cctgtccctc 60 acctgcactg tctctggtgg ctccacatcaat aattactact ggatctggat ccggcagccc 120 ccagggaagg gactggagtg gattggggtat atctatcaca gtgggagcac caactacaac 180 ccctccctca agagtcgagt caccatatca gtagacacgt ccaagaacca attctccctg 240 aaggtgagct ctgtgaccgc tgcggacacg gccgtgtatt actgtgcgaa tatggttcgg 300 ggagtttatg aagatgacta ctggggccag ggaaccctgg tcaccgtctc ctcagcctcc 360 accaagggcc catcggtctt ccccctggca ccctcctcca agagcacctc tggggggcaca 420 gcggccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540 tactccctca gcagcgtggt gaccgtgccc tccagcagct tggggcacca gacctacatc 600 tgcaacgtga atcacaagcc cagcaacacc aaggtggac agaaagttga gcccaaatct 660 tgtgacaaaa ctcacacatg cccaccgtgc ccagcacctg aactcctgggg gggaccgtca 720 gtcttcctct tccccccaaa acccaaggac accctcatga tctcccggac ccctgaggtc 780

- 406 044746

acatgcgtgg tggtggacgt gagccacgaa gaccctgagg tcaagttcaa ctggtacgtg 840 gacggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagta caacagcacg 900 taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaatgg caaggagtac 960 aagtgcaagg tctccaacaa agccctccca gcccccatcg agaaaaccat ctccaaagcc 1020 aaagggcagc cccgagaacc acaggtgtac accctgcccc catcccggga tgagctgacc 1080 aagaaccagg tcagcctgac ctgcctggtc aaaggcttct atcccagcga catcgccgtg 1140 gagtggggaga gcaatggggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1200 tccgacggct ccttcttcct ctacagcaag ctcaccgtgg acaagagcag gtggcagcag 1260 gggaacgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacgcagaag 1320 tccctctccc tgtctccggg taaatga 1347

<210> 447 <211> 448 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>447

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

5 1015

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Asn Asn Tyr 20 2530

Tyr Trp Ile Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile 35 4045

Gly Tyr Ile Tyr His Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys 50 5560

Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu 65 70 7580

Lys Val Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

Asn Met Val Arg Gly Val Tyr Glu Asp Asp Tyr Trp Gly Gln Gly Thr

100 105110

Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro

115 120125

- 407 044746

Leu Ala Pro Ser Ser

130

Lys Ser Thr Ser Gly 135

Gly Thr Ala Ala Leu 140

Cys Leu Val Lys Asp 145

Tyr Phe Pro Glu Pro 150

Val Thr Val Ser Trp 155

Ser Gly Ala Leu Thr

165

Ser Gly Val His Thr

170

Phe Pro Ala Val Leu

175

Ser Ser Gly Leu Tyr

180

Ser Leu Ser Ser Val

185

Val Thr Val Pro Ser

190

Ser Leu Gly Thr Gln

195

Thr Tyr Ile Cys Asn 200

Val Asn His Lys Pro

205

Asn Thr Lys Val Asp 210

Lys Lys Val Glu Pro

215

Lys Ser Cys Asp Lys

220

His Thr Cys Pro Pro 225

Cys Pro Ala Pro Glu 230

Leu Leu Gly Gly Pro 235

Val Phe Leu Phe Pro

245

Pro Lys Pro Lys Asp

250

Thr Leu Met Ile Ser

255

Thr Pro Glu Val Thr

260

Cys Val Val Val Asp

265

Val Ser His Glu Asp

270

Glu Val Lys Phe Asn

275

Trp Tyr Val Asp Gly 280

Val Glu Val His Asn

285

Lys Thr Lys Pro Arg

290

Glu Glu Gln Tyr Asn

295

Ser Thr Tyr Arg Val

300

Ser Val Leu Thr Val 305

Leu His Gln Asp Trp 310

Leu Asn Gly Lys Glu 315

Lys Cys Lys Val Ser

325

Asn Lys Ala Leu Pro

330

Ala Pro Ile Glu Lys

335

Ile Ser Lys Ala Lys

340

Gly Gln Pro Arg Glu

345

Pro Gln Val Tyr Thr

350

Pro Pro Ser Arg Asp

355

Glu Leu Thr Lys Asn 360

Gln Val Ser Leu Thr

365

Leu Val Lys Gly Phe

370

Tyr Pro Ser Asp Ile

375

Ala Val Glu Trp Glu

380

Gly

Asn 160

Gln

Ser

Ser

Thr

Ser 240

Arg

Pro

Ala

Val

Tyr 320

Thr

Leu

Cys

Ser

- 408 044746

Asn Gly Gln Pro Glu Asn Asn Tyr

385 390

Lys Thr Thr Pro Pro Val Leu Asp

395 400

Ser Asp Gly Ser Phe Phe Leu Tyr 405

Ser Lys Leu Thr Val Asp Lys Ser

410 415

Arg Trp Gln Gln Gly Asn Val Phe 420

Ser Cys Ser Val Met His Glu Ala

425 430

Leu His Asn His Tyr Thr Gln Lys

435 440

Ser Leu Ser Leu Ser Pro Gly Lys

445 <210> 448 <211> 645 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 448 gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggcaagtca gagcattagc aactatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctttgct gcctccagtt tgcgaagtgg ggtcccatca 180 aggttcagtg gcagtggatc tggacagat ttcactctca ccatcagcag tctgcaccct 240 gaagatttg caactacta ctgtcaacag aattacaata cccccctcac tttcggccct 300 gggaccaaag tggatatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcaggggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 645

<210> 449 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 449

Asp Ile Gln Met Thr Gln Ser Pro 1 5

Ser Ser Leu Ser Ala Ser Val Gly

15

- 409 044746

Asp Arg

Leu Asn

Phe Ala 50

Ser Gly 65

Glu Asp

Thr Phe

Pro Ser

Thr Ala

130

Lys Val 145

Glu Ser

Ser Thr

Ala Cys

Val Thr 20

Trp Tyr 35

Ala Ser

Ser Gly

Phe Ala

Gly Pro

100

Val Phe 115

Ser Val

Gln Trp

Val Thr

Leu Thr

180

Glu Val 195

Phe Asn Arg

210 <210>

<211>

<212>

<213>

<220>

<223>

Ile Thr

Gln Gln

Ser Leu

Thr Asp 70

Thr Tyr 85

Gly Thr

Ile Phe

Val Cys

Lys Val

150

Glu Gln 165

Leu Ser

Thr His

Gly Glu Cys

CysArg

Lys Pro 40

Arg Ser 55

Phe Thr

Tyr Cys

Lys Val

Pro Pro

120

Leu Leu 135

Asp Asn

Asp Ser

Lys Ala

Gln Gly

200

Ala Ser 25

Gly Lys

Gly Val

Leu Thr

Gln Gln

Asp Ile 105

Ser Asp

Asn Asn

Ala Leu

Lys Asp

170

Asp Tyr 185

Leu Ser

450

366

DNA

Artificial sequence

Synthetic

Gln Ser

Ala Pro

Pro Ser

Ile Ser 75

Asn Tyr

Lys Arg

Glu Gln

Phe Tyr

140

Gln Ser 155

Ser Thr

Glu Lys

Ser Pro gaggtgcagc tggtggagtc tggaggaggc ttgatccagc

Ile Ser

Lys Leu 45

Arg Phe

Ser Leu

Asn Thr

Thr Val

110

Leu Lys 125

Pro Arg

Gly Asn

Tyr Ser

His Lys

190

Val Thr 205

Asn Tyr

Leu Ile

Ser Gly

His Pro

Pro Leu 95

Ala Ala

Ser Gly

Glu Ala

Ser Gln

160

Leu Ser 175

Val Tyr

Lys Ser ctggggggtc cctgagactc <400>

450

- 410 044746

tcctgtgcag cctctgtgtt caccgtcagt tacaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180 gactccgtga aggggccgatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agccctcccc 300 gggtggggtg ggagcttcga gtactttgac tactggggcc agggaaccct ggtcaccgtc 360

tcctca

366 <210> 451 <211> 122 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>451

Glu 1 Val Gln Leu Val 5 Glu Ser Gly Gly Gly 10 Leu Ile Gln Pro Gly 15 Gly Ser Leu Arg Leu 20 Ser Cys Ala Ala Ser 25 Val Phe Thr Val Ser 30 Tyr Asn Tyr Met Ser 35 Trp Val Arg Gln Ala 40 Pro Gly Lys Gly Leu 45 Glu Trp Val Ser Val 50 Ile Tyr Ser Gly Gly 55 Ser Thr Tyr Tyr Ala 60 Asp Ser Val Lys Gly 65 Arg Phe Thr Ile Ser 70 Arg Asp Asn Ser Lys 75 Asn Thr Leu Tyr Leu 80 Gln Met Asn Ser Leu 85 Arg Ala Glu Asp Thr 90 Ala Val Tyr Tyr Cys 95 Ala Arg Ala Leu Pro 100 Gly Trp Gly Gly Ser 105 Phe Glu Tyr Phe Asp 110 Tyr Trp

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115120 <210>452 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

- 411 044746 <400>452 gtgttcaccg tcagttacaa ctac <210>453 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>453

Val Phe Thr Val Ser Tyr Asn Tyr <210>454 <211>48 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>454 gcgagagccc tccccgggtg gggtgggagc ttcgagtact ttgactac <210>455 <211>16 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>455

Ala Arg Ala Leu Pro Gly Trp Gly Gly Ser Phe Glu Tyr Phe Asp Tyr 1 5 1015 <210>456 <211>321 <212> DNA <213> Artificial sequence

Synthetic

456 <220>

<223>

<400>

gacatccaga atcacttgcc gggaaagccc aggttcagcg gatgattttg tgacccagtc gggccagtca ctaagctcct gcagtggatc caacttatta tccttccacc gagtattagt gatctataag tgggacagaa ctgccaacag ctgtctgcat agttggttgg gcatctagtt ttcactctca tata atagtt ctgtaggaga cctggtatca tagaaagtgg ccatcagcag attctgtgac cagagtcacc gcagaaacca ggtctcatca cctgcagcct gttcggccaa

120

180

240

300

- 412 044746 gggaccaagg tggaaatcaa a

321 <210> 457 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>457

Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Trp 20 2530

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Lys Ala Ser Ser Leu Glu Ser Gly Val Ser Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser Val 85 9095

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100105 <210>458 <211>18 <212>DNA <213>Artificial sequence <220>

<223> Synthetic <400>458 cagagtatta gtagttgg <210>459 <211>6 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 459

- 413 044746

Gln Ser Ile Ser Ser Trp < 210> 460 < 211> 9 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>460 aaggcatct <210>461 <211>27 <212>DNA <213>Artificial sequence <220>

<223> Synthetic <400>461 caacagtata atagttattc tgtgacg <210>462 <211>9 <212> PROTEIN <213>Artificial sequence <220>

<223> Synthetic <400>462

Gln Gln Tyr Asn Ser Tyr Ser Val Thr 15 <210>463 <211>1359 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 463 gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca gggtggggtg tggtggagtc cctctgtgtt ggctggagtg agggccgatt gcctgagagc ggagcttcga tggaggaggc caccgtcagt ggtctcagtt ca ccatctcc cgaggacacg gtactttgac ttgatccagc tacaactaca atttatagcg agagacaatt gccgtgtatt tactggggcc ctggggggtc tgagctgggt gtggtagcac ccaagaacac actgtgcgag agggaaccct cctgagactc ccgccaggct atactacgca gctgtatctt agccctcccc ggt caccgtc

120

180

240

300

360

- 414 044746

tcctcagcct ccaccaaggg cccacggtc ttccccctgg caccctcctc caagagcacc 420 tctggggggca cagcggccct gggctgcctg gtcaaggact acttccccga accggtgacg 480 gtgtcgtgga actcaggcgc cctgaccagc ggcgtgcaca ccttcccggc tgtcctacag 540 tcctcaggac tctactccct cagcagcgtg gtgaccgtgc cctccagcag cttggggcacc 600 cagacctaca tctgcaacgt gaatcacaag cccagcaaca ccaaggtgga caagaaagtt 660 gagcccaaat cttgtgacaa aactcacaca tgccaccgt gccagcacc tgaactcctg 720 gggggaccgt cagtcttcct cttcccccca aaacccaagg acaccctcat gatctcccgg 780 acccctgagg tcacatgcgt ggtggtggac gtgagccacg aagaccctga ggtcaagttc 840 aactggtacg tggacggcgt ggaggtgcat aatgccaaga caaagccgcg ggagaggagcag 900 tacaacagca cgtaccgtgt ggtcagcgtc ctcaccgtcc tgcaccagga ctggctgaat 960 ggcaagggagt acaagtgcaa ggtctccaac aaagccctcc cagcccccat cgagaaaacc 1020 atctccaaag ccaaagggca gccccgagaa ccacaggtgt acaccctgcc cccacccgg 1080 gatgagctga ccaagaacca ggtcagcctg acctgcctgg tcaaaggctt ctatcccagc 1140 gacatcgccg tggagtggga gagcaatggg cagccggaga acaactacaa gaccacgcct 1200 cccgtgctgg actccgacgg ctccttcttc ctctacagca agctcaccgt ggacaagagc 1260 aggtggcagc aggggaacgt cttctcatgc tccgtgatgc atgaggctct gcacaaccac 1320 tacacgcaga agtccctctc cctgtctccg ggtaaatga 1359

<210> 464 <211> 452 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 464

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Ile Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Val Phe Thr Val Ser Tyr Asn 25 30

Tyr Met Ser Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Ser Gly Gly Ser

55

Thr Tyr Tyr Ala Asp Ser Val Lys 60

Gly Arg Phe Thr Ile Ser Arg Asp

Asn Ser Lys Asn Thr Leu Tyr Leu

- 415 044746

Gln Met Asn Ser Leu

Arg Ala Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Ala Leu Pro Gly

100

Trp Gly Gly Ser Phe

105

Glu Tyr Phe Asp Tyr

110

Gly Gln Gly Thr Leu 115

Val Thr Val Ser Ser

120

Ala Ser Thr Lys Gly 125

Ser Val Phe Pro Leu

130

Ala Pro Ser Ser Lys 135

Ser Thr Ser Gly Gly 140

Ala Ala Leu Gly Cys 145

Leu Val Lys Asp Tyr 150

Phe Pro Glu Pro Val 155

Val Ser Trp Asn Ser

165

Gly Ala Leu Thr Ser

170

Gly Val His Thr Phe

175

Ala Val Leu Gln Ser

180

Ser Gly Leu Tyr Ser

185

Leu Ser Ser Val Val

190

Val Pro Ser Ser Ser

195

Leu Gly Thr Gln Thr 200

Tyr Ile Cys Asn Val

205

His Lys Pro Ser Asn

210

Thr Lys Val Asp Lys

215

Lys Val Glu Pro Lys

220

Cys Asp Lys Thr His 225

Thr Cys Pro Pro Cys 230

Pro Ala Pro Glu Leu 235

Gly Gly Pro Ser Val

245

Phe Leu Phe Pro Pro

250

Lys Pro Lys Asp Thr

255

Met Ile Ser Arg Thr

260

Pro Glu Val Thr Cys

265

Val Val Val Asp Val

270

His Glu Asp Pro Glu

275

Val Lys Phe Asn Trp

280

Tyr Val Asp Gly Val

285

Val His Asn Ala Lys

290

Thr Lys Pro Arg Glu

295

Glu Gln Tyr Asn Ser 300

Tyr Arg Val Val Ser 305

Val Leu Thr Val Leu 310

His Gln Asp Trp Leu 315

Ala

Trp

Pro

Thr

Thr 160

Pro

Thr

Asn

Ser

Leu 240

Leu

Ser

Glu

Thr

Asn 320

- 416 044746

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

325 330335

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

340 345350

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

355 360365

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

370 375380

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

385 390 395400

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

405 410415

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

420 425430

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

435 440445

Ser Pro Gly Lys

450

<210> 465 <211> 645 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 465 gacatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggccagtca gagtattagt agttggttgg cctggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctataag gcatctagtt tagaaagtgg ggtctcatca 180 aggttcagcg gcagtggatc tggacagaa ttcactctca ccatcagcag cctgcagcct 240 gatgattttg caacttatta ctgccaacag tataatagtt attctgtgac gttcggccaa 300 gggaccaagg tggaaatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540

- 417 044746 ctgagcaaag cagactacga gaaacacaaa ctgagctcgc ccgtcacaaa gagcttcaac gtctacgcct gcgaagtcac ccatcagggc aggggagagt gttag

600

645 <210> 466 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 466

Asp Ile 1

Gln Met

Thr Gln 5

Ser Pro

Ser Thr

Leu Ser

Ala Ser

Asp Arg

Val Thr

Ile Thr

CysArg

Ala Ser 25

Gln Ser

Ile Ser

Leu Ala

Trp Tyr 35

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

Lys Leu 45

Tyr Lys 50

Ala Ser

Ser Leu

Glu Ser 55

Gly Val

Ser Ser

Arg Phe

Val Gly 15

Ser Trp

Leu Ile

Ser Gly

Ser Gly 65

Ser Gly

Thr Glu

Phe Thr

Leu Thr

Ile Ser 75

Ser Leu

Glin Pro

Asp Asp

Phe Ala

Thr Tyr 85

Tyr Cys

Gln Gln

Tyr Asn

Ser Tyr

Ser Val 95

Thr Phe

Gly Gln

100

Gly Thr

Lys Val

Glu Ile 105

Lys Arg

Thr Val

110

Ala Ala

Pro Ser

Val Phe 115

Ile Phe

Pro Pro

120

Ser Asp

Glu Gln

Leu Lys 125

Ser Gly

Thr Ala

130

Ser Val

Val Cys

Leu Leu 135

Asn Asn

Phe Tyr

140

Pro Arg

Glu Ala

Lys Val 145

Gln Trp

Lys Val

150

Asp Asn

Ala Leu

Gln Ser 155

Gly Asn

Ser Gln

160

Glu Ser

Val Thr

Glu Gln 165

Asp Ser

Lys Asp

170

Ser Thr

Tyr Ser

Leu Ser 175

Ser Thr

Leu Thr

180

Leu Ser

Lys Ala

Asp Tyr 185

Glu Lys

His Lys

190

Val Tyr

- 418 044746

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195

200

205

Phe Asn Arg Gly Glu Cys 210 <210> 467 <211> 363 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>467 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc60 tcctgtgcag cctctggact caccgtcagt agcaactaca tgagctgggt ccgccaggct120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagtac attctacgca180 gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gttgtatctt240 cagatgaaca gcctgagacc tgaggacacg gctgtgtatt actgtgcgag agaggccgt300 atagcagcaa ctggctacgg tatggacgtc tgggg ccaag ggaccacggt caccgtctcc360 tca

363 <210>468 <211>121 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 468

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Leu Thr Val Ser Ser Asn

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu

Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Ala

- 419 044746

Arg Glu Gly Arg

100

Ile Ala Ala Thr Gly Tyr Gly Met Asp Val Trp Gly

105 110

Gln Gly Thr Thr Val Thr Val Ser Ser

115 120 <210> 469 <211> 45 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 469 gcgagagagg gccgtatagc agcaactggc tacggtatgg acgtc <210> 470 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 470

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

5 10 15

471

321

DNA

Artificial

Synthetic

471 <210>

<211>

<212>

<213>

<220>

<223>

<400>

gacatccaga atcacttgcc gggaaagccc aggttcagtg gaagatattg gggaccaaag sequence tgacccagtc aggcgagtca ctaagctcct gaagtagatc cgacatatta tggatatcaa tccatcctcc ggacattagc gatctacgat tgggacagat ctgtcatcag a ctgtctgcat aactatttaa gcat ccaatt tttactttca tatgataatc ctgtaggaga attggtatca tgggaacagg ccatcagcag tccctcaaac cagagtcacc gcagaaacca ggtcccatca cctgcagcct tttcggccct

120

180

240

300

321 <210> 472 <211> 107 <212> PROTEIN <213> Artificial sequence

- 420 044746 <220>

<223> Synthetic <400> 472

Asp Ile Gln Met 1

Thr Gln Ser Pro 5

Ser Ser Leu Ser 10

Ala Ser Val Gly 15

Asp Arg Val Thr 20

Ile Thr Cys Gln

Ala Ser Gln Asp 25

Ile Ser Asn Tyr 30

Leu Asn Trp Tyr

Gln Gln Lys Pro 40

Gly Lys Ala Pro

Lys Leu Leu Ile 45

Tyr Asp Ala Ser 50

Asn Leu Gly Thr 55

Gly Val Pro Ser 60

Arg Phe Ser Gly

Ser Arg Ser Gly 65

Thr Asp Phe Thr 70

Phe Thr Ile Ser

Ser Leu Gln Pro

Glu Asp Ile Ala

Thr Tyr Tyr Cys 85

His Gln Tyr Asp 90

Asn Leu Pro Gln

Thr Phe Gly Pro

100

Gly Thr Lys Val

Asp Ile Lys 105 <210> 473 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>473 catcagtatg ataatctccc tcaaact <210>474 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>474

His Gln Tyr Asp Asn Leu Pro Gln Thr <210>475 <211>1356 <212> DNA

- 421 044746 <213> Artificial sequence <220>

<223> Synthetic <400>475 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc60 tcctgtgcag cctctggact caccgtcagt agcaactaca tgagctgggt ccgccaggct120 ccagggaagg ggctggagtg ggtctcagt t atttatagcg gtggtagtac attctacgca180 gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gttgtatctt240 cagatgaaca gcctgagacc tgaggacacg gctgtgtatt actgtgcgag agaggggccgt300 atagcagcaa ctggctacgg tatggacgtc tgg ggccaag ggaccacggt caccgtctcc360 tcagcctcca ccaagggccc atcggtcttc cccctggcac cctcctccaa gagcacctct420 gggggcacag cggccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg480 tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc540 tcaggactct actccctcag cagcgtggtg accgtgccct ccagcagctt gggcaccag6 00 acctacatct gcaacgtgaa tcacaagccc agcaacacca aggtggacaa gaaagttgag660 cccaaatctt gtgacaaaac tcacacatgc ccaccgtgcc cagcacctga actcctgggg720 ggaccgtcag tcttcctctt ccccccaaaa cccaaggaca ccctcatgat ctcccggacc7 80 cctgaggtca catgcgtggt ggtggacgtg agccacgaag accctgaggt caagttcaac840 tggtacgtgg acggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagtac900 aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaatggc960 aaggagtaca agtgcaaggt ctccaacaaa gccctcccag cccccatcga gaaaaccatc1020 tccaaagcca aagggcagcc ccgagaacca caggtgtaca ccctgccccc atcccgggat1080 gagctgacca agaacc aggt cagcctgacc tgcctggtca aaggcttcta tcccagcgac1140 atcgccgtgg agtggggagag caatgggcag ccggagaaca actacaagac cacgcctccc1200 gtgctggact ccgacggctc cttcttcctc tacagcaagc tcaccgtgga caagagcagg1260 tggcag cagg ggaacgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac1320 acgcagaagt ccctctccct gtctccgggt aaatga1356 <210>476 <211 >451 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 476

- 422 044746

Glu 1

Ser

Tyr

Ser

Gly 65

Gln

Arg

Gln

Val

Ala 145

Ser

Val

Pro

Lys

Asp 225

Gly

Val Gln Leu Val Glu

Leu Arg Leu Ser Cys 20

Met Ser Trp Val Arg 35

Val Ile Tyr Ser Gly 50

Arg Phe Thr Ile Ser 70

Met Asn Ser Leu Arg 85

Glu Gly Arg Ile Ala

100

Gly Thr Thr Val Thr 115

Phe Pro Leu Ala Pro 130

Leu Gly Cys Leu Val

150

Trp Asn Ser Gly Ala

165

Leu Gln Ser Ser Gly 180

Ser Ser Ser Leu Gly 195

Pro Ser Asn Thr Lys 210

Lys Thr His Thr Cys

230

Pro Ser Val Phe Leu

245

Ser Gly Gly Gly Leu

Ala Ala Ser Gly Leu 25

Gln Ala Pro Gly Lys 40

Gly Ser Thr Phe Tyr 55

Arg Asp Asn Ser Lys 75

Pro Glu Asp Thr Ala 90

Ala Thr Gly Tyr Gly 105

Val Ser Ser Ala Ser

120

Ser Ser Lys Ser Thr 135

Lys Asp Tyr Phe Pro

155

Leu Thr Ser Gly Val

170

Leu Tyr Ser Leu Ser 185

Thr Gln Thr Tyr Ile 200

Val Asp Lys Lys Val 215

Pro Pro Cys Pro Ala

235

Phe Pro Pro Lys Pro

250

Val Gln Pro Gly Gly

Thr Val Ser Ser Asn

Gly Leu Glu Trp Val 45

Ala Asp Ser Val Lys 60

Asn Thr Leu Tyr Leu 80

Val Tyr Tyr Cys Ala

Met Asp Val Trp Gly

110

Thr Lys Gly Pro Ser

125

Ser Gly Gly Thr Ala 140

Glu Pro Val Thr Val

160

His Thr Phe Pro Ala

175

Ser Val Val Thr Val

190

Cys Asn Val Asn His

205

Glu Pro Lys Ser Cys 220

Pro Glu Leu Leu Gly

240

Lys Asp Thr Leu Met

255

- 423 044746

Ile Ser

Arg Thr

260

Pro Glu

Val Thr

Glu Asp

Pro Glu 275

Val Lys

Phe Asn

280

His Asn

290

Ala Lys

Thr Lys

Pro Arg 295

Arg Val 305

Val Ser

Val Leu

310

Thr Val

Cys Val 265

Trp Tyr

Glu Glu

Leu His

Val Val

Val Asp

Gln Tyr

300

Gln Asp 315

Lys Glu

Tyr Lys

Cys Lys 325

Val Ser

Asn Lys

330

Ala Leu

Glu Lys

Thr Ile

340

Ser Lys

Ala Lys

Gly Gln 345

Pro Arg

Tyr Thr

Leu Pro 355

Pro Ser

Arg Asp

360

Glu Leu

Thr Lys

Asp Val

270

Gly Val 285

Asn Ser

Trp Leu

Pro Ala

Glu Pro

350

Asn Gln 365

Ser His

Glu Val

Thr Tyr

Asn Gly

320

Pro Ile 335

Gln Val

Val Ser

Leu Thr

370

Cys Leu

Val Lys

Gly Phe 375

Tyr Pro

Ser Asp

380

Ile Ala

Val Glu

Trp Glu 385

Ser Asn

Gly Gln

390

Pro Glu

Asn Asn

Tyr Lys 395

Thr Thr

Pro Pro

400

Val Leu

Asp Ser

Asp Gly 405

Ser Phe

Phe Leu

410

Tyr Ser

Lys Leu

Thr Val 415

Asp Lys

Ser Arg

420

Trp Gln

Gln Gly

Asn Val 425

Phe Ser

Cys Ser

430

Val Met

His Glu

Ala Leu 435

His Asn

His Tyr

440

Thr Gln

Lys Ser

Leu Ser 445

Leu Ser

Pro Gly Lys

450 <210>

<211>

<212>

<213>

477

645

DNA

Artificial sequence <220>

<223>

Synthetic <400>

477 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc

- 424 044746

atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctacgat gcatccaatt tgggaacagg ggtcccatca 180 aggttcagtg gaagtagatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaagatattg cgacatatta ctgtcatcag tatgataatc tccctcaaac tttcggccct 300 gggaccaaag tggatatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcaggggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 645

<210> 478 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>478

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Asp Ala Ser Asn Leu Gly Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Arg Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Ile Ala Thr Tyr Tyr Cys His Gln Tyr Asp Asn Leu Pro Gln 85 9095

Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Arg Thr Val Ala Ala

100 105110

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

115 120125

- 425 044746

Thr Ala Ser Val Val Cys Leu Leu

130 135

Asn Asn Phe Tyr Pro Arg Glu Ala

140

Lys Val Gln Trp Lys Val Asp Asn

145 150

Ala Leu Gln Ser Gly Asn Ser Gln

155 160

Glu Ser Val Thr Glu Gln Asp Ser

165

Lys Asp Ser Thr Tyr Ser Leu Ser

170 175

Ser Thr Leu Thr Leu Ser Lys Ala 180

Asp Tyr Glu Lys His Lys Val Tyr

185 190

Ala Cys Glu Val Thr His Gln Gly

195 200

Leu Ser Ser Pro Val Thr Lys Ser

205

Phe Asn Arg Gly Glu Cys

210 <210> 479 <211> 342 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 479

gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatcccg gtggtagtac attctacgca 180 gactccgtga aggggatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatcaacgc 300 gattttgcct ggggccaggg aaccctggtc accgtctcct ca 342

<210> 480 <211> 114 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>480

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser 2025

Gly Phe Thr Val Ser Ser Asn

- 426 044746

Tyr Met Ser Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Pro Gly Gly Ser

55

Thr Phe Tyr Ala Asp Ser Val Lys 60

Gly Arg Phe Thr Ile Ser Arg Asp 65 70

Asn Ser Lys Asn Thr Leu Tyr Leu

80

Gln Met Asn Ser Leu Arg Ala Glu 85

Asp Thr Ala Val Tyr Tyr Cys Ala

95

Arg Asp Gln Arg Asp Phe Ala Trp

100

Gly Gln Gly Thr Leu Val Thr Val

105 110

Ser Ser <210> 481 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>481 ggattcaccg tcagtagcaa ctac <210>482 <211>21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>482 atttatcccg gtggtagtac a <210>483 <211>7 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>483

Ile Tyr Pro Gly Gly Ser Thr

5

- 427 044746 <210> 484 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>484 gcgagagatc aacgcgattt tgcc <210>485 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>485

Ala Arg Asp Gln Arg Asp Phe Ala <210>486 <211>321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 486

gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccaccagcgg cctgcagcct 240 gaagatattg caacatatta ctgtcaacag tatgataatc tccctccgac cttcggccaa 300 gggacacgac tggagattaa a 321

<210> 487 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 487

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

- 428 044746

Asp Arg Val Thr Ile Thr Cys Gln 20

Ala Ser Gln Asp Ile Ser Asn Tyr 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro

40

Gly Lys Ala Pro Lys Leu Leu Ile 45

Tyr Asp Ala Ser Asn Leu Glu Thr

55

Gly Val Pro Ser Arg Phe Ser Gly 60

Ser Gly Ser Gly Thr Asp Phe Thr 65 70

Phe Thr Ile Ser Gly Leu Gln Pro

80

Glu Asp Ile Ala Thr Tyr Tyr Cys 85

Gln Gln Tyr Asp Asn Leu Pro Pro

95

Thr Phe Gly Gln Gly Thr Arg Leu

100

Glu Ile Lys 105 <210> 488 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 488 caacagtatg ataatctccc tccgacc <210> 489 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>489

Gln Gln Tyr Asp Asn Leu Pro Pro Thr

5 <210> 490 <211> 1335 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 490 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctgggt ccgccaggct

120

- 429 044746

ccagggaagg ggctggagtg ggtctcagtt atttatcccg gtggtagtac attctacgca 180 gactccgtga aggggatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatcaacgc 300 gattttgcct ggggccaggg aaccctggtc accgtctcct cagcctccac caagggccca 360 tcggtcttcc ccctggcacc ctcctccaag agcacctctg ggggcacagc ggccctggggc 420 tgcctggtca aggactactt ccccgaaccg gtgacggtgt cgtggaactc aggcgccctg 480 accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc 540 agcgtggtga ccgtgccctc cagcagcttg ggcaccaga cctacatctg caacgtgaat 600 cacaagccca gcaacaccaa ggtggacag aaagttgagc ccaaatcttg tgacaaaact 660 cacacatgcc caccgtgccc agcacctgaa ctcctgggggg gaccgtcagt cttcctcttc 720 cccccaaaac ccaaggacac cctcatgatch tcccggaccc ctgaggtcac atgcgtggtg 780 gtggacgtga gccacgaaga ccctgaggtc aagttcaact ggtacgtgga cggcgtggag 840 gtgcataatg ccaagacaaa gccgcggggag gagcagtaca acagcacgta ccgtgtggtc 900 agcgtcctca ccgtcctgca ccaggactgg ctgaatggca aggagtacaa gtgcaaggtc 960 tccaacaaag ccctcccagc ccccatcgag aaaaccatct ccaaagccaa agggcagccc 1020 cgagaaccac aggtgtacac cctgccccca tcccgggatg agctgaccaa gaaccaggtc 1080 agcctgacct gcctggtcaa aggcttctat cccagcgaca tcgccgtgga gtgggagagc 1140 aatggggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc 1200 ttcttcctct acagcaagct caccgtggac aagagcaggt ggcagcaggg gaacgtcttc 1260 tcatgctccg tgatgcatga ggctctgcac aaccactaca cgcagaagtc cctctccctg 1320 tctccggggta aatga 1335

<210> 491 <211> 444 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>491

Glu Val Gln 1

Ser Leu Arg

Tyr Met Ser

Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1015

Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn 20 2530

Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 4045

- 430 044746

Ser

Gly 65

Gln

Arg

Ser

Ser

Asp 145

Thr

Tyr

Gln

Asp

Pro 225

Pro

Thr

Asn

Arg

Val Ile Tyr Pro Gly 50

Arg Phe Thr Ile Ser 70

Met Asn Ser Leu Arg 85

Asp Gln Arg Asp Phe 100

Ser Ala Ser Thr Lys 115

Lys Ser Thr Ser Gly 130

Tyr Phe Pro Glu Pro

150

Ser Gly Val His Thr

165

Ser Leu Ser Ser Val

180

Thr Tyr Ile Cys Asn 195

Lys Lys Val Glu Pro 210

Cys Pro Ala Pro Glu

230

Pro Lys Pro Lys Asp

245

Cys Val Val Val Asp

260

Trp Tyr Val Asp Gly

275

Glu Glu Gln Tyr Asn

Gly Ser Thr Phe Tyr 55

Arg Asp Asn Ser Lys 75

Ala Glu Asp Thr Ala

Ala Trp Gly Gln Gly 105

Gly Pro Ser Val Phe 120

Gly Thr Ala Ala Leu 135

Val Thr Val Ser Trp

155

Phe Pro Ala Val Leu

170

Val Thr Val Pro Ser

185

Val Asn His Lys Pro

200

Lys Ser Cys Asp Lys 215

Leu Leu Gly Gly Pro

235

Thr Leu Met Ile Ser

250

Val Ser His Glu Asp

265

Val Glu Val His Asn

280

Ser Thr Tyr Arg Val

Ala Asp Ser Val Lys 60

Asn Thr Leu Tyr Leu 80

Val Tyr Tyr Cys Ala

Thr Leu Val Thr Val

110

Pro Leu Ala Pro Ser

125

Gly Cys Leu Val Lys 140

Asn Ser Gly Ala Leu

160

Gln Ser Ser Gly Leu

175

Ser Ser Leu Gly Thr 190

Ser Asn Thr Lys Val

205

Thr His Thr Cys Pro 220

Ser Val Phe Leu Phe

240

Arg Thr Pro Glu Val

255

Pro Glu Val Lys Phe

270

Ala Lys Thr Lys Pro

285

Val Ser Val Leu Thr

- 431 044746

290

295

300

Val Leu 305

Ser Asn

Lys Gly

Asp Glu

Phe Tyr 370

Glu Asn 385

Phe Phe

Gly Asn

Tyr Thr

His Gln

Lys Ala

Glin Pro

340

Leu Thr 355

Pro Ser

Asn Tyr

Leu Tyr

Val Phe

420

Gln Lys 435

Asp Trp

310

Leu Asn

Gly Lys

Leu Pro 325

Ala Pro

Ile Glu

330

Arg Glu

Pro Gln

Val Tyr 345

Lys Asn

Gln Val

360

Ser Leu

Asp Ile

Ala Val 375

Glu Trp

Lys Thr

390

Thr Pro

Pro Val

Ser Lys 405

Ser Cys

Ser Leu

Leu Thr

Ser Val

Ser Leu

440

Val Asp

410

Met His 425

Ser Pro

Glu Tyr 315

Lys Thr

Thr Leu

Thr Cys

Glu Ser

380

Leu Asp 395

Lys Ser

Glu Ala

Gly Lys

Lys Cys

Ile Ser

Pro Pro

350

Leu Val 365

Asn Gly

Ser Asp

Arg Trp

Leu His

430

Lys Val

320

Lys Ala 335

Ser Arg

Lys Gly

Glin Pro

Gly Ser

400

Gln Gln 415

Asn His <210>

<211>

<212>

<213>

492

645

DNA

Artificial sequence <220>

<223> Synthetic <400> 492 gacatccaga atcacttgcc gggaaagccc aggttcagtg gaagatattg gggacacgac tctgatgagc cccagagagg tgacccagtc aggcgagtca ctaagctcct gaagtggatc caacatatta tggagattaa agttgaaatc ccaaagtaca tccat cctcc ggacattagc gatctacgat tgggacagat ctgtcaacag acgaactgtg tggaactgcc gtggaaggtg ctgtctgcat aactatttaa gcatccaatt tttactttca tatgataatc gctgcaccat tctgttgtgt gataacgccc ctgtaggaga attggtatca tggaaacagg ccatcagcgg t ccctccgac ctgtcttcat gcctgctgaa tccaatcggg cagagtcacc gcagaaacca ggtcccatca cctgcagcct cttcggccaa cttcccgcca taacttctat taactcccag

120

180

240

300

360

420

480

- 432 044746 caccctgacg ccatcagggc gagagtgtca ctgagcaaag ctgagctcgc cagagcagga cagactacga ccgtcacaaa cagcaaggac gaaacacaaa gagcttcaac agcacctaca gtctacgcct aggggagagt gcctcagcag gcgaagtcac gttag

540

600

645 <210> 493 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 493

Asp Ile 1

Gln Met

Thr Gln 5

Ser Pro

Ser Ser

Leu Ser

Ala Ser

Asp Arg

Val Thr

Ile Thr

Cys Gln

Ala Ser 25

Gln Asp

Ile Ser

Leu Asn

Trp Tyr 35

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

Lys Leu 45

Tyr Asp 50

Ala Ser

Asn Leu

Glu Thr 55

Gly Val

Pro Ser

Arg Phe

Val Gly 15

Asn Tyr

Leu Ile

Ser Gly

Ser Gly 65

Ser Gly

Thr Asp 70

Phe Thr

Phe Thr

Ile Ser 75

Gly Leu

Glin Pro

Glu Asp

Ile Ala

Thr Tyr 85

Tyr Cys

Gln Gln

Tyr Asp

Asn Leu

Pro Pro 95

Thr Phe

Gly Gln

100

Gly Thr

Arg Leu

Glu Ile 105

Lys Arg

Thr Val

110

Ala Ala

Pro Ser

Val Phe 115

Ile Phe

Pro Pro

120

Ser Asp

Glu Gln

Leu Lys 125

Ser Gly

Thr Ala

130

Ser Val

Val Cys

Leu Leu 135

Lys Val 145

Gln Trp

Lys Val

150

Asp Asn

Glu Ser

Val Thr

Glu Gln 165

Asp Ser

Ser Thr

Leu Thr

Leu Ser

Lys Ala

Asn Asn

Ala Leu

Lys Asp

170

Asp Tyr

Phe Tyr

140

Pro Arg

Glu Ala

Gln Ser 155

Gly Asn

Ser Gln

160

Ser Thr

Tyr Ser

Leu Ser 175

Glu Lys

His Lys

Val Tyr

- 433 044746

180

185

190

Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

195 200205

Phe Asn Arg Gly Glu Cys 210 <210>494 <211>381 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 494

caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagt agctatgcta tgcactgggt ccgccaggct 120 ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agctgaggac acggctgtgt attackgtgc gagagacggc 300 cggactatta ctatggttcg ggggagttatt gatgatgctt ttgatatctg gggccaaggg 360 acaatggtca ccgtctcttc a 381

<210> 495 <211> 127 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 495

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala

Ser Gly Phe Thr Phe Ser Ser Tyr 25 30

Ala Met His Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ala Val Ile Ser Tyr Asp Gly Ser

55

Asn Lys Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ser Lys Asn Thr Leu Tyr

80

- 434 044746

Leu Gln Met Asn Ser Leu Arg Ala 85

Ala Arg Asp Gly Arg Thr Ile Thr 100

Ala Phe Asp Ile Trp Gly Gln Gly 115120

Glu Asp Thr Ala Val Tyr Tyr Cys

9095

Met Val Arg Gly Val Ile Asp Asp

105110

Thr Met Val Thr Val Ser Ser

125 <210> 496 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>496 ggattcacct tcagtagcta tgct <210>497 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>497

Gly Phe Thr Phe Ser Ser Tyr Ala <210>498 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>498 atatcatatg atggaagtaa taaa <210>499 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 499

Ile Ser Tyr Asp Gly Ser Asn Lys

- 435 044746 <210> 500 <211> 60 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>500 gcgagagacg gccggactat tactatggtt cggggagtta ttgatgatgc ttttgatatc60 <210>501 <211>20 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>501

Ala Arg Asp Gly Arg Thr Ile Thr Met Val Arg Gly Val Ile Asp Asp

5 1015

Ala Phe Asp Ile 20 <210>502 <211>321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>502 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc60 atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca120 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaa acagg ggtcccatca180 aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct240 gaagatattg caacatatta ctgtcaacag tatgataatc tccccctcac cttcggccaa300 gggacacgac tggagattaa a321 <210>

<211>

<212>

<213>

503

107

PROTEIN

Artificial sequence <220>

<223>

Synthetic

- 436 044746 <400>503

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asp Ile Ser Asn Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Asp Ala Ser Asn Leu Glu Thr Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Pro Leu 85 9095

Thr Phe Gly Gln Gly Thr Arg Leu Glu Ile Lys

100105 <210>504 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>504 caacagtatg ataatctccc cctcacc <210>505 <211>1374 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 505

caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagt agctatgcta tgcactgggt ccgccaggct 120 ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag agctgaggac acggctgtgt attackgtgc gagagacggc 300 cggactatta ctatggttcg ggggagttatt gatgatgctt ttgatatctg gggccaaggg 360

- 437 044746

acaatggtca ccgtctcttc agcctccacc aagggcccat cggtcttccc cctggcaccc 420 tcctccaaga gcacctctgg gggcacagcg gccctgggct gcctggtcaa ggactacttc 480 cccgaaccgg tgacggtgtc gtggaactca ggcgccctga ccagcggcgt gcacaccttc 540 ccggctgtcc tacagtcctc aggactctac tccctcagca gcgtggtgac cgtgccctcc 600 agcagcttgg gcacccagac ctacatctgc aacgtgaatc acaagcccag caacaccaag 660 gtggacaaga aagttgagcc caaatcttgt gacaaaactc acacatgccc accgtgccca 720 gcacctgaac tcctgggggg accgtcagtc ttcctcttcc ccccaaaacc caaggacacc 780 ctcatgatct cccggacccc tgaggtcaca tgcgtggtgg tggacgtgag ccacgaagac 840 cctgaggtca agttcaactg gtacgtggac ggcgtggagg tgcataatgc caagacaaag 900 ccgcgggagg agcagtacaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac 960 caggactggc tgaatggcaa ggagtacaag tgcaaggtct ccaacaaagc cctcccagcc 1020 ccatcgaga aaaccatctc caaagccaaa gggcagcccc gagaaccaca ggtgtacacc 1080 ctgcccccat cccgggatga gctgaccaag aaccaggtca gcctgacctg cctggtcaaa 1140 ggcttctatc ccagcgacat cgccgtggag tggggagagca atggggcagcc ggagaacaac 1200 tacaagacca cgcctcccgt gctggactcc gacggctcct tcttcctcta cagcaagctc 1260 accgtggac agagcaggtg gcagcagggg aacgtcttct catgctccgt gatgcatgag 1320 gctctgcaca accactacac gcagaagtcc ctctccctgt ctccgggtaa atga 1374

<210> 506 <211> 457 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 506

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Ser Ser Tyr 25 30

Ala Met His Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ala Val Ile Ser Tyr Asp Gly Ser

55

Asn Lys Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ser Lys Asn Thr Leu Tyr

80

- 438 044746

Leu

Ala

Ala

Ser

Thr 145

Pro

Val

Ser

Ile

Val 225

Ala

Pro

Val

Val

Gln 305

Gln

Gln Met Asn

Ser Leu Arg 85

Ala Glu Asp

Thr Ala Val

Tyr Tyr Cys 95

Arg Asp Gly

100

Arg Thr Ile

Thr Met Val

105

Arg Gly Val

Ile Asp Asp 110

Phe Asp Ile 115

Thr Lys Gly 130

Ser Gly Gly

Glu Pro Val

His Thr Phe

180

Ser Val Val

195

Cys Asn Val 210

Glu Pro Lys

Pro Glu Leu

Lys Asp Thr

260

Val Asp Val

275

Asp Gly Val 290

Tyr Asn Ser

Asp Trp Leu

Trp Gly Gln

Gly Thr Met 120

Val Thr Val

125

Ser Ser Ala

Pro Ser Val

135

Phe Pro Leu

Ala Pro Ser

140

Ser Lys Ser

Thr Ala Ala

150

Thr Val Ser 165

Pro Ala Val

Thr Val Pro

Asn His Lys

215

Ser Cys Asp

230

Leu Gly Gly 245

Leu Met Ile

Ser His Glu

Glu Val His

295

Thr Tyr Arg

310

Asn Gly Lys

Leu Gly Cys

Leu Val Lys 155

Asp Tyr Phe

160

Trp Asn Ser

170

Leu Gln Ser

185

Ser Ser Ser 200

Pro Ser Asn

Lys Thr His

Pro Ser Val

250

Ser Arg Thr

265

Asp Pro Glu 280

Asn Ala Lys

Val Val Ser

Glu Tyr Lys

Gly Ala Leu

Thr Ser Gly

175

Ser Gly Leu

Tyr Ser Leu 190

Leu Gly Thr

205

Thr Lys Val

220

Thr Cys Pro 235

Phe Leu Phe

Pro Glu Val

Val Lys Phe

285

Thr Lys Pro

300

Val Leu Thr 315

Cys Lys Val

Gln Thr Tyr

Asp Lys Lys

Pro Cys Pro

240

Pro Pro Lys

255

Thr Cys Val 270

Asn Trp Tyr

Arg Glu Glu

Val Leu His

320

Ser Asn Lys

- 439 044746

325

330

335

Ala Leu Pro Ala Pro Ile Glu Lys 340

Thr Ile Ser Lys 345

Ala Lys Gly Gln

350

Pro Arg Glu Pro Gln Val Tyr Thr

355 360

Leu Pro Pro Ser

Arg Asp Glu Leu 365

Thr Lys Asn Gln Val Ser Leu Thr

370 375

Cys Leu Val Lys

380

Gly Phe Tyr Pro

Ser Asp Ile Ala Val Glu Trp Glu

385 390

Ser Asn Gly Gln

395

Pro Glu Asn Asn

400

Tyr Lys Thr Thr Pro Pro Val Leu 405

Asp Ser Asp Gly

410

Ser Phe Phe Leu

415

Tyr Ser Lys Leu Thr Val Asp Lys 420

Ser Arg Trp Gln 425

Gln Gly Asn Val 430

Phe Ser Cys Ser Val Met His Glu

435440

Ala Leu His Asn

His Tyr Thr Gln 445

Lys Ser Leu Ser Leu Ser Pro Gly Lys

450455 <210>507 <211>645 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>507 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc60 atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca120 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaaca gg ggtcccatca180 aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct240 gaagatattg caacatatta ctgtcaacag tatgataatc tccccctcac cttcggccaa300 gggacacgac tggagattaa acgaactgtg gctgcaccat ctgtct tcat cttcccgcca360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcagggc6 00

- 440 044746 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag

645 <210> 508 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 508

Asp 1 Ile Gln Met Thr 5 Gln Ser Pro Ser Ser 10 Leu Ser Ala Ser Val 15 Gly Asp Arg Val Thr 20 Ile Thr Cys Gln Ala 25 Ser Gln Asp Ile Ser 30 Asn Tyr Leu Asn Trp 35 Tyr Gln Gln Lys Pro 40 Gly Lys Ala Pro Lys 45 Leu Leu Ile Tyr Asp 50 Ala Ser Asn Leu Glu 55 Thr Gly Val Pro Ser 60 Arg Phe Ser Gly Ser 65 Gly Ser Gly Thr Asp 70 Phe Thr Phe Thr Ile 75 Ser Ser Leu Gln Pro 80 Glu Asp Ile Ala Thr 85 Tyr Tyr Cys Gln Gln 90 Tyr Asp Asn Leu Pro 95 Leu Thr Phe Gly Gln 100 Gly Thr Arg Leu Glu 105 Ile Lys Arg Thr Val 110 Ala Ala Pro Ser Val 115 Phe Ile Phe Pro Pro 120 Ser Asp Glu Gln Leu 125 Lys Ser Gly Thr Ala 130 Ser Val Val Cys Leu 135 Leu Asn Asn Phe Tyr 140 Pro Arg Glu Ala Lys 145 Val Gln Trp Lys Val 150 Asp Asn Ala Leu Gln 155 Ser Gly Asn Ser Gln 160 Glu Ser Val Thr Glu 165 Gln Asp Ser Lys Asp 170 Ser Thr Tyr Ser Leu 175 Ser Ser Thr Leu Thr 180 Leu Ser Lys Ala Asp 185 Tyr Glu Lys His Lys 190 Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser

- 441 044746

195 200205

Phe Asn Arg Gly Glu Cys

210 <210>509 <211>360 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>509 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc60 tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctgggt ccgccaggct120 ccagggaagg ggctggagtg ggtctcag tt atttatagcg gtggtagtac atactacgca180 gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt240 caaatgaaca gactgagagc tgacgacacg gctgtctatt actgtgtgag agatccggtg300 gggcgctact actacggtat ggacgtctgg ggccaa ggga ccacggtcac cgtctcctca360 < 210>510 < 211 >120 < 212> PROTEIN < 213> Artificial sequence < 220>

< 223> Synthetic < 400>510

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Arg Leu Arg Ala Asp Asp Thr Ala Val Tyr Tyr Cys Val 85 9095

- 442 044746

Arg Asp Pro Val Gly Arg Tyr Tyr

100

Tyr Gly Met Asp Val Trp Gly Gln

105 110

Gly Thr Thr Val Thr Val Ser Ser

115120 <210>511 <211>42 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>511 gtgagagatc cggtggggcg ctactactac ggtatggacg tc <210>512 <211>14 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>512

Val Arg Asp Pro Val Gly Arg Tyr Tyr Tyr Gly Met Asp Val

510 <210>513 <211>321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 513

gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc aggcgagtca ggacattaac aactatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaagatattg caacatatta ttgtcaacag tatgataatc tccctcgcac tttcggcgga 300 gggaccaagg tggagatcaa a 321

<210> 514 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic

- 443 044746 <400> 514

Asp Ile Gln Met 1

Asp Arg Val Thr

Thr Gln Ser Pro 5

Ile Thr Cys Gln

Leu Asn Trp Tyr

Gln Gln Lys Pro 40

Tyr Asp Ala Ser 50

Asn Leu Glu Thr

Ser Ser Leu Ser 10

Ala Ser Gln Asp 25

Gly Lys Ala Pro

Gly Val Pro Ser 60

Ala Ser Val Gly 15

Ile Asn Asn Tyr 30

Lys Leu Leu Ile 45

Arg Phe Ser Gly

Ser Gly Ser Gly 65

Thr Asp Phe Thr 70

Phe Thr Ile Ser

Ser Leu Gln Pro

Glu Asp Ile Ala

Thr Tyr Tyr Cys 85

Gln Gln Tyr Asp 90

Asn Leu Pro Arg 95

Thr Phe Gly Gly

100

Gly Thr Lys Val

Glu Ile Lys 105 <210> 515 <211> 18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>515 caggacatta acaactat <210>516 <211>6 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>516

Gln Asp Ile Asn Asn Tyr <210>517 <211>27 <212> DNA <213> Artificial sequence <220>

- 444 044746 <223> Synthetic <400>517 caacagtatg ataatctccc tcgcact <210>518 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>518

Gln Gln Tyr Asp Asn Leu Pro Arg Thr 15 < 210 > 519 < 211 > 1353 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic

<400> 519 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagtac atactacgca 180 gactccgtga aggggccgatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gactgagagc tgacgacacg gctgtctatt actgtgtgag agatccggtg 300 ggggcgctact actacggtat ggacgtctgg ggccaaggga ccacggtcac cgtctcctca 360 gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacacc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcggggaga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020

- 445 044746

aaagccaaag ggcagccccg agaaccacag gtgtacacc tgcccccatc ccgggatgag 1080 ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140 gccgtggagt ggggagagcaa tggggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1260 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320 cagaagtccc tctccctgtc tccggggtaaa tga 1353

<210> 520 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>520

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser 2025

Tyr Met Ser Trp Val Arg Gln Ala Pro 3540

Gly Phe Thr Val Ser Ser Asn 30

Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Arg Leu Arg Ala Asp Asp Thr Ala Val Tyr Tyr Cys Val 85 9095

Arg Asp Pro Val Gly Arg Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln

100 105110

Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val

115 120125

Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala

130 135140

Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser

145 150 155160

- 446 044746

Trp Asn Ser Gly Ala

165

Leu Thr Ser Gly Val

170

His Thr Phe Pro Ala

175

Leu Gln Ser Ser Gly

180

Leu Tyr Ser Leu Ser

185

Ser Val Val Thr Val

190

Ser Ser Ser Leu Gly 195

Thr Gln Thr Tyr Ile 200

Cys Asn Val Asn His

205

Pro Ser Asn Thr Lys 210

Val Asp Lys Lys Val

215

Glu Pro Lys Ser Cys

220

Lys Thr His Thr Cys 225

Pro Pro Cys Pro Ala 230

Pro Glu Leu Leu Gly 235

Pro Ser Val Phe Leu

245

Phe Pro Pro Lys Pro

250

Lys Asp Thr Leu Met

255

Ser Arg Thr Pro Glu

260

Val Thr Cys Val Val

265

Val Asp Val Ser His

270

Asp Pro Glu Val Lys

275

Phe Asn Trp Tyr Val

280

Asp Gly Val Glu Val

285

Asn Ala Lys Thr Lys 290

Pro Arg Glu Glu Gln

295

Tyr Asn Ser Thr Tyr 300

Val Val Ser Val Leu 305

Thr Val Leu His Gln 310

Asp Trp Leu Asn Gly 315

Glu Tyr Lys Cys Lys

325

Val Ser Asn Lys Ala

330

Leu Pro Ala Pro Ile

335

Lys Thr Ile Ser Lys

340

Ala Lys Gly Gln Pro

345

Arg Glu Pro Gln Val

350

Thr Leu Pro Pro Ser

355

Arg Asp Glu Leu Thr 360

Lys Asn Gln Val Ser

365

Thr Cys Leu Val Lys

370

Gly Phe Tyr Pro Ser

375

Asp Ile Ala Val Glu

380

Glu Ser Asn Gly Gln 385

Pro Glu Asn Asn Tyr 390

Lys Thr Thr Pro Pro 395

Leu Asp Ser Asp Gly

405

Ser Phe Phe Leu Tyr

410

Ser Lys Leu Thr Val

415

Val

Pro

Lys

Asp

Gly 240

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

Leu

Trp

Val 400

Asp

- 447 044746

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser

Cys Ser Val Met His

420

425

430

Glu Ala Leu His Asn His Tyr Thr

Gln Lys Ser Leu Ser Leu Ser Pro

435 440

445

Gly Lys

450

<210> 521 <211> 645 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 521 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc aggcgagtca ggacattaac aactatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180 aggttcagtg gaagtggatc tggacagat tttacttttca ccatcagcag cctgcagcct 240 gaagatattg caacatatta ttgtcaacag tatgataatc tccctcgcac tttcggcgga 300 gggaccaagg tggagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcaggggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 645

<210> 522 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 522

Asp Ile Gln Met Thr Gln Ser Pro 1 5

Ser Ser Leu Ser Ala Ser Val Gly

15

Asp Arg Val Thr Ile Thr Cys Gln 20

Ala Ser Gln Asp Ile Asn Asn Tyr 25 30

- 448 044746

Leu Asn

Tyr Asp 50

Ser Gly 65

Glu Asp

Trp Tyr 35

Ala Ser

Ser Gly

Ile Ala

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

Thr Phe

Gly Gly

100

Pro Ser

Val Phe

115

Thr Ala

130

Ser Val

Asn Leu

Thr Asp 70

Thr Tyr 85

Gly Thr

Ile Phe

Val Cys

Glu Thr 55

Gly Val

Pro Ser

Phe Thr

Phe Thr

Ile Ser 75

Tyr Cys

Lys Val

Pro Pro

120

Leu Leu 135

Gln Gln

Tyr Asp

Lys Leu 45

Arg Phe

Ser Leu

Asn Leu

Leu Ile

Ser Gly

Glin Pro

Pro Arg 95

Glu Ile 105

Lys Arg

Thr Val

110

Ala Ala

Ser Asp

Glu Gln

Leu Lys 125

Ser Gly

Asn Asn

Phe Tyr

140

Pro Arg

Glu Ala

Lys Val 145

Gln Trp

Lys Val

150

Asp Asn

Ala Leu

Gln Ser 155

Gly Asn

Ser Gln

160

Glu Ser

Val Thr

Glu Gln 165

Asp Ser

Lys Asp

170

Ser Thr

Tyr Ser

Leu Ser 175

Ser Thr

Leu Thr

180

Leu Ser

Lys Ala

Asp Tyr 185

Glu Lys

His Lys

190

Val Tyr

Ala Cys

Glu Val 195

Thr His

Gln Gly

200

Leu Ser

Ser Pro

Val Thr 205

Lys Ser

Phe Asn Arg

210

Gly Glu Cys <210> 523 <211> 351 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 523 gaggtgcagc tggtggagtc tggaggaggc tcctgtgcag cctctggggt caccgtcagt ccagggaagg ggctggagtg ggtctcagtc ttgatccagc ctggggggtc cctgagactc agcaactaca tgagctgggt ccgccaggct attta tagcg gcggtagcac attctactca

120

180

- 449 044746

gactccgtga aggggccgatt cagcatctcc agagacaatt ccaagaacac actgtatctt 240 caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agacctctac 300 tactacggta tggacgtctg gggccaaggg accacggtca ccgtctcctc a 351

<210> 524 <211> 117 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>524

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Val Thr Val Ser Ser Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ser Asp Ser Val Lys 50 5560

Gly Arg Phe Ser Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

Arg Asp Leu Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105110

Val Thr Val Ser Ser

115 <210>525 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>525 ggggtcaccg tcagtagcaa ctac <210>526 <211>21

- 450 044746 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>526 atttatagcg gcggtagcac a <210>527 <211>33 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>527 gcgagagacc tctactacta cggtatggac gtc <210>528 <211>11 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>528

Ala Arg Asp Leu Tyr Tyr Tyr Gly Met Asp Val

510 <210>529 <211>324 <212> DNA <213> Artificial sequence

Synthetic

529 <220>

<223>

<400>

g catccactt ttcactctca cttgatagtt ctgtaggaga cctggtatca tgcaaagtgg caatcagcag accctgggct cagagtcacc gcaaaaacca ggtcccatca cctgcagcct cactttcggc

120

180

240

300

324 <210> 530 <211> 108 <212> PROTEIN <213> Artificial sequence

- 451 044746 <220>

<223> Synthetic <400>530

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

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Thr Tyr 20 2530

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asp Ser Tyr Pro Gly 85 9095

Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100105 <210>531 <211>18 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>531 cagggcatta gcacttat <210>532 <211>6 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>532

Gln Gly Ile Ser Thr Tyr <210>533 <211>30 <212> DNA <213> Artificial sequence

- 452 044746 <220>

<223> Synthetic <400>533 caacagcttg atagttaccc tgggctcact <210>534 <211>10 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>534

Gln Gln Leu Asp Ser Tyr Pro Gly Leu Thr

510 < 210> 535 < 211> 1344 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic

<400> 535 gaggtgcagc tggtggagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtc atttatagcg gcggtagcac attctactca 180 gactccgtga aggggccgatt cagcatctcc agagacaatt ccaagaacac actgtatctt 240 caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agacctctac 300 tactacggta tggacgtctg gggccaaggg accacggtca ccgtctcctc agcctccacc 360 aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc 600 aacgtgaatc acaagcccag caacaccaag gtggacaaga aagttgagcc caaatcttgt 660 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 720 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 780 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 840 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 900 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 960

- 453 044746 tgcaaggtct gggcagcccc aaccaggtca tgggagagca gacggctcct aacgtcttct ctctccctgt ccaacaaagc gagaaccaca gcctgacctg atgggcagcc tcttcctcta catgctccgt ctccgggtaa cctcccagcc ggtgtacacc cctggtcaaa ggagaacaac cagcaagctc gatgcatgag atga cccatcgaga ctgcccccat ggcttctatc tacaagacca accgtggaca gctctgcaca aaaccatctc cccgggatga ccagcgacat cgcctcccgt agagcaggtg accactacac caaagccaaa gctgaccaag cgccgtggag gctggactcc gcagcagg gg gcagaagtcc

1020

1080

1140

1200

1260

1320

1344 <210> 536 <211> 447 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>536

Glu Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly 10

Leu Ile

Glin Pro

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Val Thr

Val Ser

Tyr Met

Ser Trp 35

Val Arg

Gln Ala

Pro Gly

Lys Gly

Leu Glu 45

Ser Val

Ile Tyr

Ser Gly

Gly Ser 55

Thr Phe

Tyr Ser 60

Asp Ser

Gly Gly 15

Ser Asn

Trp Val

Val Lys

Gly Arg 65

Phe Ser

Ile Ser

Arg Asp

Asn Ser

Lys Asn 75

Thr Leu

Tyr Leu 80

Gln Met

Asn Ser

Leu Arg 85

Ala Glu

Asp Thr

Ala Val

Tyr Tyr

Cys Ala 95

Arg Asp

Leu Tyr

100

Tyr Tyr

Gly Met

Asp Val 105

Trp Gly

Gln Gly

110

Thr Thr

Val Thr

Val Ser

115

Ser Ala

Ser Thr

120

Lys Gly

Pro Ser

Val Phe 125

ProLeu

Ala Pro

130

Ser Ser

Lys Ser

Thr Ser 135

Gly Gly

Thr Ala

140

Ala Leu

Gly Cys

Leu Val 145

Lys Asp

Tyr Phe

150

Pro Glu

Pro Val

Thr Val 155

Ser Trp

Asn Ser

160

- 454 044746

Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe

170

Pro Ala Val Leu Gln

175

Ser Gly Leu Tyr Ser

180

Leu Ser Ser Val Val

185

Thr Val Pro Ser Ser

190

Leu Gly Thr Gln Thr 195

Tyr Ile Cys Asn Val 200

Asn His Lys Pro Ser 205

Thr Lys Val Asp Lys

210

Lys Val Glu Pro Lys

215

Ser Cys Asp Lys Thr

220

Thr Cys Pro Pro Cys 225

Pro Ala Pro Glu Leu 230

Leu Gly Gly Pro Ser 235

Phe Leu Phe Pro Pro

245

Lys Pro Lys Asp Thr

250

Leu Met Ile Ser Arg

255

Pro Glu Val Thr Cys

260

Val Val Val Asp Val

265

Ser His Glu Asp Pro

270

Val Lys Phe Asn Trp

275

Tyr Val Asp Gly Val

280

Glu Val His Asn Ala

285

Thr Lys Pro Arg Glu

290

Glu Gln Tyr Asn Ser

295

Thr Tyr Arg Val Val

300

Val Leu Thr Val Leu 305

His Gln Asp Trp Leu 310

Asn Gly Lys Glu Tyr 315

Cys Lys Val Ser Asn

325

Lys Ala Leu Pro Ala

330

Pro Ile Glu Lys Thr

335

Ser Lys Ala Lys Gly

340

Gln Pro Arg Glu Pro

345

Gln Val Tyr Thr Leu

350

Pro Ser Arg Asp Glu

355

Leu Thr Lys Asn Gln 360

Val Ser Leu Thr Cys 365

Val Lys Gly Phe Tyr

370

Pro Ser Asp Ile Ala

375

Val Glu Trp Glu Ser

380

Gly Gln Pro Glu Asn 385

Asn Tyr Lys Thr Thr 390

Pro Pro Val Leu Asp 395

Ser

Ser

Asn

His

Val 240

Thr

Glu

Lys

Ser

Lys 320

Ile

Pro

Leu

Asn

Ser 400

Arg

Asp Gly Ser Phe Phe

Leu Tyr Ser Lys Leu

Thr Val Asp Lys Ser

- 455 044746

405 410 415

Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

420 425 430

His Asn His

435

Tyr Thr Gln Lys Ser Leu

Ser Leu Ser Pro Gly Lys

440

445

<210> 537 <211> 648 <212> DNA <213> Artificial subsequence <220> <223> Synthetic <400> 537 gacatccagt tgaccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggccagtca gggcattagc acttatttag cctggtatca gcaaaaacca 120 gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180 aggttcagcg gcagtggatc tggacagaa ttcactctca caatcagcag cctgcagcct 240 gaagatttg caacttatta ctgtcaacag cttgatagtt accctggggct cactttcggc 300 ggagggacca aggtggagat caaacgaact gtggctgcac catctgtctt catcttcccg 360 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420 tatccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 648

<210> 538 <211> 215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>538

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

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Thr Tyr 20 2530

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

- 456 044746

Tyr Ala 50

Ser Gly 65

Glu Asp

Leu Thr

Ala Pro

Ala Ser

Ser Gly

Phe Ala

Phe Gly

100

Ser Val 115

Thr Leu

Thr Glu

Thr Tyr 85

Gly Gly

Phe Ile

Gly Thr

130

Ala Ser

Val Val

Ala Lys 145

Val Gln

Trp Lys

150

Gln Glu

Ser Val

Thr Glu 165

Ser Ser

Thr Leu

180

Thr Leu

Tyr Ala

Cys Glu 195

Val Thr

Ser Phe Asn Arg Gly Glu

210

Gln Ser 55

Phe Thr

Tyr Cys

Thr Lys

Phe Pro

120

Cys Leu 135

Val Asp

Gln Asp

Ser Lys

His Gln

200

Cys 215

Gly Val

Leu Thr

Gln Gln

Val Glu 105

Pro Ser

Leu Asn

Asn Ala

Ser Lys

170

Ala Asp 185

Gly Leu <210> 539 <211> 1335 <212> DNA <213> Artificial sequence

Synthetic

539 <220>

<223>

<400>

caggtgcagc acctgcactg ccagggaagg ccctccctca tgcaggagtc tctctggtgg gactggagtg agagtcgagt gggcccagga ctccatcaat gattgggtat caccatatca

Pro Ser

Ile Ser 75

Leu Asp

Ile Lys

Asp Glu

Asn Phe

140

Leu Gln 155

Asp Ser

Tyr Glu

Ser Ser ctggtgaagc aattactact atctatcaca gtagacacgt

Arg Phe

Ser Leu

Ser Tyr

Arg Thr

110

Gln Leu 125

Tyr Pro

Ser Gly

Thr Tyr

Lys His

190

Pro Val 205 cttcggagac ggatctggat gtgggagcac ccaagaacca

Ser Gly

Glin Pro

Pro Gly 95

Val Ala

Lys Ser

Arg Glu

Asn Ser

160

Ser Leu 175

Lys Val

Thr Lys cctgtccctc ccggcagccc caactacaac attctccctg

120

180

240

- 457 044746

aaggtgagct ctgtgaccgc tgcggacacg gccgtgtatt actgtgcgaa tatggttcgg 300 ggagtttatg aagatgacta ctggggccag ggaaccctgg tcaccgtctc ctcagcctcc 360 accaagggcc catcggtctt ccccctggcg ccctgctcca ggagcacctc cgagagcaca 420 gccgccctgg gctgcctggt caaggactac ttccccgaac cggtgacggt gtcgtggaac 480 tcaggcgccc tgaccagcgg cgtgcacacc ttcccggctg tcctacagtc ctcaggactc 540 tactccctca gcagcgtggt gaccgtgccc tccagcagct tggggcacgaa gacctacacc 600 tgcaacgtag atcacaagcc cagcaacacc aaggtggac agagagttga gtccaaatat 660 ggtcccccat gccaccgtg cccagcacca ggcggtggcg gaccatcagt cttcctgttc 720 cccccaaaac ccaaggacac tctcatgatch tcccggaccc ctgaggtcac gtgcgtggtg 780 gtggacgtga gccaggaaga ccccgaggtc cagttcaact ggtacgtgga tggcgtggag 840 gtgcataatg ccaagacaaa gccgcggggag gagcagttca acagcacgta ccgtgtggtc 900 agcgtcctca ccgtcctgca ccaggactgg ctgaacggca aggagtacaa gtgcaaggtc 960 tccaacaaag gcctcccgtc ctccatcgag aaaaccatct ccaaagccaa agggcagccc 1020 cgagagccac aggtgtacac cctgccccca tccggagagg agatgaccaa gaaccaggtc 1080 agcctgacct gcctggtcaa aggcttctac cccagcgaca tcgccgtgga gtgggagagc 1140 aatggggcagc cggagaacaa ctacaagacc acgcctcccg tgctggactc cgacggctcc 1200 ttcttcctct acagcaggct caccgtggac aagagcaggt ggcaggaggg gaatgtcttc 1260 tcatgctccg tgatgcatga ggctctgcac aaccactaca cacagaagtc cctctccctg 1320 tctctggggta aatga 1335

<210> 540 <211> 444 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>540

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

5 1015

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Asn Asn Tyr 20 2530

Tyr Trp Ile Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile 35 4045

Gly Tyr Ile Tyr His Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys 50 5560

- 458 044746

Ser 65

Lys

Asn

Leu

Leu

Cys 145

Ser

Ser

Ser

Asn

Pro 225

Pro

Thr

Asn

Arg

Val

Arg Val Thr Ile Ser 70

Val Ser Ser Val Thr

Met Val Arg Gly Val 100

Val Thr Val Ser Ser

115

Ala Pro Cys Ser Arg 130

Leu Val Lys Asp Tyr

150

Gly Ala Leu Thr Ser

165

Ser Gly Leu Tyr Ser 180

Leu Gly Thr Lys Thr

195

Thr Lys Val Asp Lys 210

Pro Cys Pro Ala Pro

230

Pro Lys Pro Lys Asp

245

Cys Val Val Val Asp

260

Trp Tyr Val Asp Gly

275

Glu Glu Gln Phe Asn 290

Leu His Gln Asp Trp

Val Asp Thr Ser Lys

Ala Ala Asp Thr Ala

Tyr Glu Asp Asp Tyr 105

Ala Ser Thr Lys Gly 120

Ser Thr Ser Glu Ser 135

Phe Pro Glu Pro Val

155

Gly Val His Thr Phe

170

Leu Ser Ser Val Val

185

Tyr Thr Cys Asn Val

200

Arg Val Glu Ser Lys 215

Gly Gly Gly Gly Pro

235

Thr Leu Met Ile Ser

250

Val Ser Gln Glu Asp

265

Val Glu Val His Asn

280

Ser Thr Tyr Arg Val 295

Leu Asn Gly Lys Glu

Asn Gln Phe Ser Leu

Val Tyr Tyr Cys Ala

Trp Gly Gln Gly Thr

110

Pro Ser Val Phe Pro

125

Thr Ala Ala Leu Gly 140

Thr Val Ser Trp Asn

160

Pro Ala Val Leu Gln

175

Thr Val Pro Ser Ser

190

Asp His Lys Pro Ser 205

Tyr Gly Pro Pro Cys 220

Ser Val Phe Leu Phe

240

Arg Thr Pro Glu Val

255

Pro Glu Val Gln Phe

270

Ala Lys Thr Lys Pro

285

Val Ser Val Leu Thr 300

Tyr Lys Cys Lys Val

- 459 044746

305

310

315

320

Ser Asn

Lys Gly

Lys Gly

Glin Pro

340

Glu Glu

Met Thr 355

Phe Tyr

370

Pro Ser

Glu Asn 385

Asn Tyr

Phe Phe

Leu Tyr

Gly Asn

Val Phe

420

Tyr Thr

Gln Lys 435

Leu Pro 325

Arg Glu

Lys Asn

Asp Ile

Lys Thr 390

Ser Arg 405

Ser Cys

Ser Leu

Ser Ser

Ile Glu

330

Lys Thr

Ile Ser

Pro Gln

Gln Val

360

Ala Val 375

Thr Pro

Leu Thr

Ser Val

Ser Leu

440

Val Tyr 345

Thr Leu

Pro Pro

350

Ser Leu

Thr Cys

Leu Val 365

Glu Trp

Glu Ser

380

Asn Gly

Pro Val

Leu Asp 395

Ser Asp

Val Asp

410

Met His 425

Ser Leu <210> 541 <211> 1347 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 541 gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca gggtggggtg tcctcagcct tccgagagca gtgtcgtgga tcctcaggac tggtggagtc cctctgtgtt ggctggagtg agggccgatt gcctgagagc ggagcttcga ccaccaaggg cagccgccct actcaggcgc tctactccct tggaggaggc caccgtcagt ggtctcagtt caccatctcc cgaggacacg gtactttgac cccatcggtc gggctgcctg cctgaccagc cagcagcgtg

Lys Ser

Glu Ala

Gly Lys ttgatccagc tacaactaca atttatagcg agagacaatt gccgtgtatt tactggggcc ttccccctgg gtcaaggact ggcgtgcaca gtgaccgtgc

Arg Trp

Leu His

430

Lys Ala 335

Ser Gln

Lys Gly

Glin Pro

Gly Ser 400

Gln Glu 415

Asn His ctggggggtc tgagctgggt gtggtagcac ccaagaacac actgtgcgag agggaaccct cgccctgctc acttccccga ccttcccggc cctccagcag cctgagactc ccgccaggct atactacgca gctgtatctt agccctcccc ggtcaccgtc caggagcacc accggtgacg tgtcctacag cttggggcacg

120

180

240

300

360

420

480

540

600

- 460 044746

aagactaca cctgcaacgt agatcacaag cccagcaaca ccaaggtgga caagagagtt 660 gagtccaaat atggtccccc atgcccaccg tgcccagcac caggcggtgg cggaccatca 720 gtcttcctgt tccccccaaa acccaaggac actctcatga tctcccggac ccctgaggtc 780 acgtgcgtgg tggtggacgt gagccaggaa gaccccgagg tccagttcaa ctggtacgtg 840 gatggcgtgg aggtgcataa tgccaagaca aagccgcggg aggagcagtt caacagcacg 900 taccgtgtgg tcagcgtcct caccgtcctg caccaggact ggctgaacgg caaggagtac 960 aagtgcaagg tctccaacaa aggcctcccg tcctccatcg agaaaaccat ctccaaagcc 1020 aaagggcagc cccgagagcc acaggtgtac accctgcccc catccagga ggagatgacc 1080 aagaaccagg tcagcctgac ctgcctggtc aaaggcttct accccagcga catcgccgtg 1140 gagtggggaga gcaatggggca gccggagaac aactacaaga ccacgcctcc cgtgctggac 1200 tccgacggct ccttcttcct ctacagg ctcaccgtgg acaagagcag gtggcaggag 1260 gggaatgtct tctcatgctc cgtgatgcat gaggctctgc acaaccacta cacacagaag 1320 tccctctccc tgtctctggg taaatga 1347

<210> 542 <211> 448 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 542

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Ile Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Val Phe Thr Val Ser Tyr Asn 25 30

Tyr Met Ser Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Ser Gly Gly Ser

55

Thr Tyr Tyr Ala Asp Ser Val Lys 60

Gly Arg Phe Thr Ile Ser Arg Asp 65 70

Asn Ser Lys Asn Thr Leu Tyr Leu

80

Gln Met Asn Ser Leu Arg Ala Glu 85

Asp Thr Ala Val Tyr Tyr Cys Ala

95

Arg Ala Leu Pro Gly Trp Gly Gly

Ser Phe Glu Tyr Phe Asp Tyr Trp

- 461 044746

100

105

110

Gly Gln Gly Thr Leu 115

Val Thr Val Ser Ser

120

Ala Ser Thr Lys Gly 125

Ser Val Phe Pro Leu

130

Ala Pro Cys Ser Arg

135

Ser Thr Ser Glu Ser

140

Ala Ala Leu Gly Cys 145

Leu Val Lys Asp Tyr 150

Phe Pro Glu Pro Val 155

Val Ser Trp Asn Ser

165

Gly Ala Leu Thr Ser

170

Gly Val His Thr Phe

175

Ala Val Leu Gln Ser

180

Ser Gly Leu Tyr Ser

185

Leu Ser Ser Val Val

190

Val Pro Ser Ser Ser

195

Leu Gly Thr Lys Thr 200

Tyr Thr Cys Asn Val

205

His Lys Pro Ser Asn

210

Thr Lys Val Asp Lys

215

Arg Val Glu Ser Lys

220

Gly Pro Pro Cys Pro 225

Pro Cys Pro Ala Pro 230

Gly Gly Gly Gly Pro 235

Val Phe Leu Phe Pro

245

Pro Lys Pro Lys Asp

250

Thr Leu Met Ile Ser

255

Thr Pro Glu Val Thr

260

Cys Val Val Val Asp

265

Val Ser Gln Glu Asp

270

Glu Val Gln Phe Asn

275

Trp Tyr Val Asp Gly 280

Val Glu Val His Asn

285

Lys Thr Lys Pro Arg

290

Glu Glu Gln Phe Asn

295

Ser Thr Tyr Arg Val

300

Ser Val Leu Thr Val 305

Leu His Gln Asp Trp 310

Leu Asn Gly Lys Glu 315

Lys Cys Lys Val Ser

325

Asn Lys Gly Leu Pro

330

Ser Ser Ile Glu Lys

335

Ile Ser Lys Ala Lys

340

Gly Gln Pro Arg Glu

345

Pro Gln Val Tyr Thr

350

Pro

Thr

Thr 160

Pro

Thr

Asp

Tyr

Ser 240

Arg

Pro

Ala

Val

Tyr 320

Thr

Leu

- 462 044746

Pro Pro Ser Gln Glu Glu Met Thr

355 360

Lys Asn Gln Val Ser Leu Thr Cys

365

Leu Val Lys Gly Phe Tyr Pro Ser

370 375

Asp Ile Ala Val Glu Trp Glu Ser 380

Asn Gly Gln Pro Glu Asn Asn Tyr

385 390

Lys Thr Thr Pro Pro Val Leu Asp

395 400

Ser Asp Gly Ser Phe Phe Leu Tyr 405

Ser Arg Leu Thr Val Asp Lys Ser

410 415

Arg Trp Gln Glu Gly Asn Val Phe 420

Ser Cys Ser Val Met His Glu Ala

425 430

Leu His Asn His Tyr Thr Gln Lys

435 440

Ser Leu Ser Leu Ser Leu Gly Lys

445

<210> 543 <211> 1344 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 543 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggact caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagtac attctacgca 180 gactccgtga aggggccgatt caccattctcc agagacaatt ccaagaacac gttgtatctt 240 cagatgaaca gcctgagacc tgaggacacg gctgtgtatt actgtgcgag aggggccgt 300 atagcagcaa ctggctacgg tatggacgtc tggggccaag ggaccacggt caccgtctcc 360 tcagcctcca ccaagggccc atcggtcttc cccctggcgc cctgctccag gagcacctcc 420 gagagcacag ccgccctggg ctgcctggtc aaggactact tccccgaacc ggtgacggtg 480 tcgtggaact caggcgccct gaccagcggc gtgcacacct tcccggctgt cctacagtcc 540 tcaggactct actccctcag cagcgtggtg accgtgccct ccagcagctt gggcacgaag 600 acctacacct gcaacgtaga tcacaagccc agcaacacca aggtggacaa gagagttgag 660 tccaaatatg gtcccccatg cccaccgtgc ccagcaccag gcggtggcgg accatcagtc 720 ttcctgttcc ccccaaaacc caaggacact ctcatgatct cccggacccc tgaggtcacg 780 tgcgtggtgg tggacgtgag caggaagac cccgaggtcc agttcaactg gtacgtggat 840 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagttcaa cagcacgtac 900

- 463 044746 cgtgtggtca tgcaaggtct gggcagcccc aaccaggtca tgggagagca gacggctcct aatgtcttct ctctccctgt gcgtcctcac ccaacaaagg gagagccaca gcctgacctg atgggcagcc tcttcctcta catgctccgt ctctgggtaa cgtcc tgcac cctcccgtcc ggtgtacacc cctggtcaaa ggagaacaac cagcaggctc gatgcatgag atga caggactggc tccatcgaga ctgcccccat ggcttctacc tacaagacca accgtggaca gctctgcaca tgaacggcaa aaaccatctc cccaggagga ccagcgacat cgcctcccgt agagcaggt g accactacac ggagtacaag caaagccaaa gatgaccaag cgccgtggag gctggactcc gcaggagggg acagaagtcc

960

1020

1080

1140

1200

1260

1320

1344 <210> 544 <211> 447 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>544

Glu Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly 10

Leu Val

Glin Pro

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Leu Thr

Val Ser

Tyr Met

Ser Trp 35

Val Arg

Gln Ala

Pro Gly

Lys Gly

Leu Glu 45

Ser Val

Ile Tyr

Ser Gly

Gly Ser 55

Thr Phe

Tyr Ala 60

Asp Ser

Gly Gly 15

Ser Asn

Trp Val

Val Lys

Gly Arg 65

Phe Thr

Ile Ser

Arg Asp

Asn Ser

Lys Asn 75

Thr Leu

Tyr Leu 80

Gln Met

Asn Ser

Leu Arg 85

Pro Glu

Asp Thr

Ala Val

Tyr Tyr

Cys Ala 95

Arg Glu

Gly Arg

100

Ile Ala

Ala Thr

Gly Tyr 105

Gly Met

Asp Val

110

Trp Gly

Gln Gly

Thr Thr 115

Val Thr

Val Ser

120

Ser Ala

Ser Thr

Lys Gly 125

Pro Ser

Val Phe

130

ProLeu

Ala Pro

Cys Ser 135

Arg Ser

Thr Ser

140

Glu Ser

Thr Ala

- 464 044746

Ala 145

Ser

Val

Pro

Lys

Pro 225

Phe

Pro

Val

Thr

Val 305

Cys

Ser

Pro

Val

Gly 385

Leu Gly Cys

Trp Asn Ser

Leu Gln Ser

180

Ser Ser Ser

195

Pro Ser Asn 210

Pro Cys Pro

Leu Phe Pro

Glu Val Thr

260

Gln Phe Asn

275

Lys Pro Arg 290

Leu Thr Val

Lys Val Ser

Lys Ala Lys

340

Ser Gln Glu

355

Lys Gly Phe 370

Gln Pro Glu

Leu Val Lys

150

Gly Ala Leu 165

Ser Gly Leu

Leu Gly Thr

Thr Lys Val

215

Pro Cys Pro

230

Pro Lys Pro 245

Cys Val Val

Trp Tyr Val

Glu Glu Gln

295

Leu His Gln

310

Asn Lys Gly 325

Gly Gln Pro

Glu Met Thr

Tyr Pro Ser

375

Asn Asn Tyr

390

Asp Tyr Phe

Thr Ser Gly

170

Tyr Ser Leu

185

Lys Thr Tyr 200

Asp Lys Arg

Ala Pro Gly

Lys Asp Thr

250

Val Asp Val

265

Asp Gly Val 280

Phe Asn Ser

Asp Trp Leu

Leu Pro Ser

330

Arg Glu Pro

345

Lys Asn Gln 360

Asp Ile Ala

Lys Thr Thr

Pro Glu Pro 155

Val His Thr

Ser Ser Val

Thr Cys Asn

205

Val Glu Ser

220

Gly Gly Gly 235

Leu Met Ile

Ser Gln Glu

Glu Val His

285

Thr Tyr Arg

300

Asn Gly Lys 315

Ser Ile Glu

Gln Val Tyr

Val Ser Leu

365

Val Glu Trp

380

Pro Pro Val 395

Val Thr Val

160

Phe Pro Ala

175

Val Thr Val 190

Val Asp His

Lys Tyr Gly

Pro Ser Val

240

Ser Arg Thr

255

Asp Pro Glu 270

Asn Ala Lys

Val Val Ser

Glu Tyr Lys

320

Lys Thr Ile

335

Thr Leu Pro 350

Thr Cys Leu

Glu Ser Asn

Leu Asp Ser

400

- 465 044746

Asp Gly Ser Phe

Phe Leu Tyr Ser 405

Arg Leu Thr Val 410

Asp Lys Ser Arg

415

Trp Gln Glu Gly

420

Asn Val Phe Ser

Cys Ser Val Met 425

His Glu Ala Leu

430

His Asn His Tyr

435

Thr Gln Lys Ser

440

Leu Ser Leu Ser

Leu Gly Lys 445

<210> 545 <211> 1323 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 545 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatcccg gtggtagtac attctacgca 180 gactccgtga aggggatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatcaacgc 300 gattttgcct ggggccaggg aaccctggtc accgtctcct cagcctccac caagggccca 360 tcggtcttcc ccctggcgcc ctgctccagg agcacctccg agagcacagc cgccctggggc 420 tgcctggtca aggactactt ccccgaaccg gtgacggtgt cgtggaactc aggcgccctg 480 accagcggcg tgcacacctt cccggctgtc ctacagtcct caggactcta ctccctcagc 540 agcgtggtga ccgtgccctc cagcagcttg ggcacgaaga cctacacctg caacgtagat 600 cacaagccca gcaacaccaa ggtggacag agagttgagt ccaaatatgg tcccccatgc 660 ccaccgtgcc cagcaccagg cggtggcgga ccatcagtct tcctgttccc cccaaaaccc 720 aaggacactc tcatgatctc ccggacccct gaggtcacgt gcgtggtggt ggacgtgagc 780 caggaagacc ccgaggtcca gttcaactgg tacgtggatg gcgtggaggt gcataatgcc 840 aagacaaagc cgcggggaga gcagttcaac agcacgtacc gtgtggtcag cgtcctcacc 900 gtcctgcacc aggactggct gaacggcaag gagtacaagt gcaaggtctc caacaaaggc 960 ctcccgtcct ccatcgagaa aaccatctcc aaagccaaag ggcagccccg agagccacag 1020 gtgtacacc tgcccccatc ccaggagag atgaccaaga accaggtcag cctgacctgc 1080 ctggtcaaag gcttctaccc cagcgacatc gccgtggagt ggggagagcaa tggggcagccg 1140 gagaacaact acaagaccac gcctcccgtg ctggactccg acggctcctt cttcctctac 1200 agcaggctca ccgtggacaa gagcaggtgg caggagggga atgtcttctc atgctccgtg 1260

- 466 044746 atgcatgagg ctctgcacaa cactacaca cagaagtccc tctccctgtc tctgggtaaa

1320

1323 tga <210> 546 <211> 440 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 546

Glu Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly 10

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Tyr Met

Ser Trp 35

Val Arg

Gln Ala

Pro Gly

Ser Val

Ile Tyr

Pro Gly

Gly Ser 55

Thr Phe

Gly Arg 65

Phe Thr

Ile Ser

Arg Asp

Asn Ser

Gln Met

Asn Ser

Leu Arg 85

Ala Glu

Asp Thr

Arg Asp

Gln Arg

100

Asp Phe

Ala Trp

Gly Gln 105

Ser Ser

Ala Ser 115

Thr Lys

Gly Pro

120

Ser Val

Ser Arg

130

Ser Thr

Ser Glu

Ser Thr 135

Ala Ala

Asp Tyr 145

Phe Pro

Glu Pro

150

Val Thr

Val Ser

Thr Ser

Gly Val

His Thr 165

Phe Pro

Ala Val

170

Tyr Ser

Leu Ser

180

Ser Val

Val Thr

Val Pro 185

Leu Val

Phe Thr

Lys Gly

Tyr Ala 60

Lys Asn 75

Ala Val

Gly Thr

Phe Pro

Leu Gly

140

Trp Asn 155

Leu Gln

Ser Ser

Glin Pro

Val Ser

Leu Glu 45

Asp Ser

Gly Gly 15

Ser Asn

Trp Val

Val Lys

Thr Leu

Tyr Leu 80

Tyr Tyr

Cys Ala 95

Leu Val

110

Thr Val

Leu Ala 125

Cys Leu

Ser Gly

Ser Ser

Ser Leu

190

Pro Cys

Val Lys

Ala Leu

160

Gly Leu 175

Gly Thr

- 467 044746

Lys Thr Tyr Thr Cys 195

Asn Val Asp His Lys 200

Pro Ser Asn Thr Lys

205

Asp Lys Arg Val Glu 210

Ser Lys Tyr Gly Pro

215

Pro Cys Pro Pro Cys

220

Ala Pro Gly Gly Gly 225

Gly Pro Ser Val Phe 230

Leu Phe Pro Pro Lys 235

Lys Asp Thr Leu Met

245

Ile Ser Arg Thr Pro

250

Glu Val Thr Cys Val

255

Val Asp Val Ser Gln

260

Glu Asp Pro Glu Val

265

Gln Phe Asn Trp Tyr

270

Asp Gly Val Glu Val

275

His Asn Ala Lys Thr 280

Lys Pro Arg Glu Glu

285

Phe Asn Ser Thr Tyr 290

Arg Val Val Ser Val

295

Leu Thr Val Leu His

300

Asp Trp Leu Asn Gly 305

Lys Glu Tyr Lys Cys 310

Lys Val Ser Asn Lys 315

Leu Pro Ser Ser Ile

325

Glu Lys Thr Ile Ser

330

Lys Ala Lys Gly Gln

335

Arg Glu Pro Gln Val

340

Tyr Thr Leu Pro Pro

345

Ser Gln Glu Glu Met

350

Lys Asn Gln Val Ser

355

Leu Thr Cys Leu Val

360

Lys Gly Phe Tyr Pro

365

Asp Ile Ala Val Glu

370

Trp Glu Ser Asn Gly

375

Gln Pro Glu Asn Asn

380

Lys Thr Thr Pro Pro 385

Val Leu Asp Ser Asp 390

Gly Ser Phe Phe Leu 395

Ser Arg Leu Thr Val

405

Asp Lys Ser Arg Trp

410

Gln Glu Gly Asn Val

415

Ser Cys Ser Val Met

420

His Glu Ala Leu His

425

Asn His Tyr Thr Gln

430

Val

Pro

Pro 240

Val

Val

Gln

Gln

Gly 320

Pro

Thr

Ser

Tyr

Tyr 400

Phe

Lys

Ser Leu Ser Leu Ser

435

Leu Gly Lys

440

- 468 044746

547

369

DNA

Artificial

Synthetic

547 <210>

<211>

<212>

<213>

<220>

<223>

<400>

caggtgcagc tcctgcaagg cctggacaag gcacagaagt atggaggtga ttttactatg gtctcctca sequence tggtgcagtc cttctggagg ggcttgagtg tccaggcag gcagcctgag atagtagtgg tggggctgag caccttcagc gatgggaagg agtcacgatt atctgaggac ttatt acctt gtgaagaagc agctatgcta atcatcccta accgcggaca acggccgtgt gactactggg ctgggtcctc tcacctgggt tgtttggtat aatccacgag attactgtgc gccagggaac ggtgaaggtc gcgacaggcc agcaaactac cacagcctac gagaacaccg cctggtcacc

120

180

240

300

360

369 <210> 548 <211> 123 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>548

Gln Val Gln Leu Val Gln Ser Gly 1 5

Ala Glu Val Lys Lys Pro Gly Ser

15

Ser Val Lys Val Ser Cys Lys Ala 20

Ser Gly Gly Thr Phe Ser Ser Tyr 25 30

Ala Ile Thr Trp Val Arg Gln Ala

40

Pro Gly Gln Gly Leu Glu Trp Met 45

Gly Arg Ile Ile Pro Met Phe Gly

55

Ile Ala Asn Tyr Ala Gln Lys Phe 60

Gln Gly Arg Val Thr Ile Thr Ala 65 70

Asp Lys Ser Thr Ser Thr Ala Tyr

80

Met Glu Val Ser Ser Leu Arg Ser 85

Glu Asp Thr Ala Val Tyr Tyr Cys

95

Ala Arg Thr Pro Phe Tyr Tyr Asp

100

Ser Ser Gly Tyr Tyr Leu Asp Tyr

105 110

- 469 044746

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115

120 < 210> 549 < 211> 24 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>549 ggaggcacct tcagcagcta tgct24 <210>550 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>550

Gly Gly Thr Phe Ser Ser Tyr Ala < 210>551 < 211>24 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>551 atcatcccta tgtttggtat agca24 <210>552 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>552

Ile Ile Pro Met Phe Gly Ile Ala <210>553 <211>48 <212> DNA <213> Artificial sequence <220>

- 470 044746 gcgagaacac cgttttacta tgatagtagt ggttattacc ttgactac <223> Synthetic <400>553 <210>554 <211>16 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>554

Ala Arg Thr Pro Phe Tyr Tyr Asp Ser Ser Gly Tyr Tyr Leu Asp Tyr 1 5 1015 <210>555 <211>324 <212> DNA <213> Artificial sequence

Synthetic

555 <220>

<223>

<400>

a gcaactact ggtgcatcca gacttcactc cagtatgtta ctccagggga tagcctggta gcagggccac tcaccatcag ggtcaccccg aagagccacc ccagcagagt tggcatccca cagactggag gacgttcggc

120

180

240

300

324 <210> 556 <211> 108 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 556

Glu Ile Val Leu 1

Thr Gln Ser Pro 5

Gly Thr Leu Ser 10

Leu Ser Pro Gly 15

Glu Arg Ala Thr 20

Leu Ser Cys Arg

Ala Ser Gln Ser 25

Val Ser Ser Asn

Tyr Leu Ala Trp

Tyr Gln Gln Ser 40

Pro Gly Gln Ala

Pro Arg Leu Leu 45

- 471 044746

Ile Tyr 50 Gly Ala Ser Ser Arg Ala 55 Thr Gly Ile Pro 60 Asp Arg Phe Ser Gly 65 Ser Gly Ser Gly Thr 70 Asp Phe Thr Leu Thr 75 Ile Ser Arg Leu Glu 80 Pro Glu Asp Phe Ala 85 Val Tyr Tyr Cys Gln 90 Gln Tyr Val Arg Ser 95 Pro Arg Thr Phe Gly 100 Gln Gly Thr Lys Val 105 Glu Ile Lys

<210> 557 <211> 21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>557 cagagtgtta gcagcaacta c <210>558 <211>7 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>558

Gln Ser Val Ser Ser Asn Tyr <210>559 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>559 cagcagtatg ttaggtcacc ccggacg <210>560 <211>9 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic

- 472 044746 <400>560

Gln Gln Tyr Val Arg Ser Pro Arg Thr 15 < 210 > 561 < 211 > 1362 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic <400>561 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc60 tcctgcaagg cttctggagg caccttcagc agctatgcta tcacctgggt gcgacaggcc120 cctggacaag ggcttgagtg g atgggaagg atcatcccta tgtttggtat agcaaactac180 gcacagaagt tccagggcag agtcacgatt accgcggaca aatccacgag cacagcctac240 atggaggtga gcagcctgag atctgaggac acggccgtgt attactgtgc gagaacaccg300 ttttactatg atagtagtgg ttatt acctt gactactggg gccagggaac cctggtcacc360 gtctcctcag cctccaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc420 acctctgggg gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg480 acggtgtcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta540 cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttgg gc600 acccagacct acatctgcaa cgtgaatcac aagcccagca acaccaaggt ggacaagaaa660 gttgagccca aatcttgtga caaaactcac acatgcccac cgtgcccagc acctgaactc720 ctggggggac cgtcagtctt cctcttcccc ccaaaaccca aggacaccct catgatctcc 780 cggacccctg aggtcacatg cgtggtggtg gacgtgagcc acgaagaccc tgaggtcaag840 ttcaactggt acgtggacgg cgtggaggtg cataatgcca agacaaagcc gcgggaggag900 cagtacaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg960 aatggcaagg agtacaagtg caaggtctcc aacaaagccc tcccagcccc catcgagaaa1020 accatctcca aagccaaagg gcagccccga gaaccacagg tgtacaccct gcccccatcc1080 cgggatgagc tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctatccc1140 agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg1200 cctcccgtgc tggactccga cggctccttc ttcctctaca gcaagctcac cgtggacaag1260 agcaggtgg c agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac1320 cactacacgc agaagtccct ctccctgtct ccgggtaaat ga1362 <210> 562

- 473 044746 <211> 453 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 562

Gln Val Gln Leu Val

5

Gln Ser Gly Ala Glu

Val Lys Lys Pro Gly

Ser Val Lys Val Ser

Cys Lys Ala Ser Gly

Gly Thr Phe Ser Ser 30

Ala Ile Thr Trp Val 35

Arg Gln Ala Pro Gly 40

Gln Gly Leu Glu Trp 45

Gly Arg Ile Ile Pro 50

Met Phe Gly Ile Ala 55

Asn Tyr Ala Gln Lys 60

Gln Gly Arg Val Thr 65

Ile Thr Ala Asp Lys 70

Ser Thr Ser Thr Ala 75

Met Glu Val Ser

Leu Arg Ser Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Arg Thr Pro Phe

100

Tyr Tyr Asp Ser Ser

105

Gly Tyr Tyr Leu Asp

110

Trp Gly Gln Gly Thr 115

Leu Val Thr Val Ser

120

Ser Ala Ser Thr Lys

125

Pro Ser Val Phe Pro

130

Leu Ala Pro Ser Ser

135

Lys Ser Thr Ser Gly 140

Thr Ala Ala Leu Gly 145

Cys Leu Val Lys Asp 150

Tyr Phe Pro Glu Pro 155

Thr Val Ser Trp Asn

165

Ser Gly Ala Leu Thr

170

Ser Gly Val His Thr

175

Pro Ala Val Leu Gln

180

Ser Ser Gly Leu Tyr

185

Ser Leu Ser Ser Val

190

Thr Val Pro Ser Ser

195

Ser Leu Gly Thr Gln 200

Thr Tyr Ile Cys Asn

205

Asn His Lys Pro Ser 210

Asn Thr Lys Val Asp 215

Lys Lys Val Glu Pro

220

Ser

Tyr

Met

Phe

Tyr 80

Cys

Tyr

Gly

Gly

Val 160

Phe

Val

Val

Lys

- 474 044746

Ser Cys Asp 225

Lys Thr His

230

Thr Cys Pro

Pro Cys Pro

235

Ala Pro Glu

Leu Gly Gly

Pro Ser Val

245

Phe Leu Phe

Pro Pro Lys 250

Pro Lys Asp

255

Leu Met Ile

Ser Arg Thr 260

Pro Glu Val

265

Thr Cys Val

Val Val Asp

270

Ser His Glu

275

Asp Pro Glu

Val Lys Phe

280

Asn Trp Tyr

Val Asp Gly 285

Glu Val His

290

Asn Ala Lys

Thr Lys Pro 295

Arg Glu Glu

300

Gln Tyr Asn

Thr Tyr Arg 305

Val Val Ser

310

Val Leu Thr

Val Leu His

315

Gln Asp Trp

Asn Gly Lys

Glu Tyr Lys

325

Cys Lys Val

Ser Asn Lys 330

Ala Leu Pro

335

Pro Ile Glu

Lys Thr Ile 340

Ser Lys Ala

345

Lys Gly Gln

Pro Arg Glu

350

Gln Val Tyr

355

Thr Leu Pro

Pro Ser Arg

360

Asp Glu Leu

Thr Lys Asn 365

Val Ser Leu

370

Thr Cys Leu

Val Lys Gly 375

Phe Tyr Pro

380

Ser Asp Ile

Val Glu Trp 385

Glu Ser Asn

390

Gly Gln Pro

Glu Asn Asn

395

Tyr Lys Thr

Pro Pro Val

Leu Asp Ser

405

Asp Gly Ser

Phe Phe Leu 410

Tyr Ser Lys

415

Thr Val Asp

Lys Ser Arg 420

Trp Gln Gln

425

Gly Asn Val

Phe Ser Cys

430

Val Met His

435

Glu Ala Leu

His Asn His

440

Tyr Thr Gln

Lys Ser Leu 445

Leu 240

Thr

Val

Val

Ser

Leu 320

Ala

Pro

Gln

Ala

Thr 400

Leu

Ser

Ser

Leu Ser Pro

450

Gly Lys <210> 563

- 475 044746 <211> 648 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 563

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 ctctcttgca gggccagtca gagtgttagc agcaactact tagcctggta ccagcagagt 120 cctggccagg ctcccaggct cctcatcatat ggtgcatcca gcaggggccac tggcatccca 180 gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240 cctgaagatt ttgcagttta ttactgtcag cagtatgtta ggtcaccccg gacgttcggc 300 caagggacca aggtggaaat caaacgaact gtggctgcac catctgtctt catcttcccg 360 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420 tatccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 648

<210> 564 <211> 215 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>564

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

5 1015

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Asn 20 2530

Tyr Leu Ala Trp Tyr Gln Gln Ser Pro Gly Gln Ala Pro Arg Leu Leu 35 4045

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser 50 5560

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu 65 70 7580

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Val Arg Ser Pro 85 9095

- 476 044746

Arg Thr

Phe Gly

100

Gln Gly

Thr Lys

Ala Pro

Ser Val 115

Phe Ile

Phe Pro

120

Gly Thr

130

Ala Ser

Val Val

Cys Leu 135

Ala Lys 145

Val Gln

Trp Lys

150

Val Asp

Gln Glu

Ser Val

Thr Glu 165

Gln Asp

Ser Ser

Thr Leu

180

Thr Leu

Ser Lys

Tyr Ala

Cys Glu 195

Val Thr

His Gln

200

Val Glu 105

Pro Ser

Leu Asn

Asn Ala

Ser Lys 170

Ala Asp 185

Gly Leu

Ile Lys

Asp Glu

Asn Phe

140

Leu Gln 155

Asp Ser

Tyr Glu

Ser Ser

Arg Thr

110

Gln Leu 125

Tyr Pro

Ser Gly

Thr Tyr

Lys His

190

Pro Val 205

Val Ala

Lys Ser

Arg Glu

Asn Ser

160

Ser Leu 175

Lys Val

Thr Lys

Ser Phe Asn Arg Gly Glu Cys

210 215 <210> 565 <211> 1362 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 565 caggtgcagc tcctgtgcag ccaggcaagg gcagactccg ctgcaaatga cggactatta acaatggtca tgctccagga cccgaaccgg ccggctgtcc tggtggagtc cctctggatt ggctggagtg tgaagggccg acagcctgag ctatggttcg ccg tctcttc gcacctccga tgacggtgtc tacagtcctc tgggggaggc caccttcagt ggtggcagtt attcaccatc agctgaggac gggagttatt agcctccacc gagcacagcc gtggaactca aggactctac gtggtccagc agctatgcta atatcatatg tccagagaca acggctgtgt gatgat gctt aagggcccat gccctgggct ggcgccctga tccctcagca ctgggaggtc tgcactgggt atggaagtaa attccaagaa attactgtgc ttgatatctg cggtcttccc gcctggtcaa ccagcggcgt gcgtggtgac cctgagactc ccgccaggct taaatactac cacgctgtat gagagacggc gggccaaggg cctggcgccc ggactacttc gcacaccttc cgtgccctcc

120

180

240

300

360

420

480

540

600

- 477 044746 agcagcttgg gtggacaaga ggtggcggac cggacccctg ttcaactggt cagttcaaca aacggcaagg accatctcca caggaggaga agcgacatcg cctcccgtgc agcaggtggc cactacacac gcacgaagac gagttgagtc catcagtctt aggtcacgtg ac gtggatgg gcacgtaccg agtacaagtg aagccaaagg tgaccaagaa ccgtggagtg tggactccga aggaggggaa agaagtccct ctacacctgc caaatatggt cctgttcccc cgtggtggtg cgtggaggtg tgtggtcagc caaggtctcc gcagccccga ccaggtcagc ggagagca at cggctccttc tgtcttctca ctccctgtct aacgtagatc cccccatgcc ccaaaaccca gacgtgagcc cataatgcca gtcctcaccg aacaaaggcc gagccacagg ctgacctgcc gggcagccgg ttcctctaca tgctccgtga ctgggtaaat acaagcccag caccgtgccc aggacactct aggaagaccc agacaaagcc tcctgcacca tcccgtcctc tgtacaccct tggtcaaagg agaacaacta gcaggctcac tgcatgaggc ga caacaccaag agcaccaggc catgatctcc cgaggtccag gcgggaggag ggactggctg catcgagaaa gcccccatcc cttctacccc caagaccacg cgtggacaag tctgcacaac

660

720

780

840

900

960

1020

1080

1140

1200

1260

1320

1362 <210> 566 <211> 453 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 566

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Ser Ser Tyr 25 30

Ala Met His Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ala Val Ile Ser Tyr Asp Gly Ser

55

Asn Lys Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ser Lys Asn Thr Leu Tyr

80

Leu Gln Met Asn Ser Leu Arg Ala 85

Glu Asp Thr Ala Val Tyr Tyr Cys

95

Ala Arg Asp Gly Arg Thr Ile Thr

100

Met Val Arg Gly Val Ile Asp Asp

105 110

- 478 044746

Ala Phe Asp Ile Trp 115

Gly Gln Gly Thr Met 120

Val Thr Val Ser Ser

125

Ser Thr Lys Gly Pro 130

Ser Val Phe Pro Leu

135

Ala Pro Cys Ser Arg 140

Thr Ser Glu Ser Thr 145

Ala Ala Leu Gly Cys 150

Leu Val Lys Asp Tyr 155

Pro Glu Pro Val Thr

165

Val Ser Trp Asn Ser

170

Gly Ala Leu Thr Ser

175

Val His Thr Phe Pro

180

Ala Val Leu Gln Ser

185

Ser Gly Leu Tyr Ser

190

Ser Ser Val Val Thr

195

Val Pro Ser Ser Ser

200

Leu Gly Thr Lys Thr

205

Thr Cys Asn Val Asp

210

His Lys Pro Ser Asn

215

Thr Lys Val Asp Lys

220

Val Glu Ser Lys Tyr 225

Gly Pro Pro Cys Pro 230

Pro Cys Pro Ala Pro 235

Gly Gly Gly Pro Ser

245

Val Phe Leu Phe Pro

250

Pro Lys Pro Lys Asp

255

Leu Met Ile Ser Arg

260

Thr Pro Glu Val Thr

265

Cys Val Val Val Asp

270

Ser Gln Glu Asp Pro

275

Glu Val Gln Phe Asn

280

Trp Tyr Val Asp Gly

285

Glu Val His Asn Ala

290

Lys Thr Lys Pro Arg

295

Glu Glu Gln Phe Asn

300

Thr Tyr Arg Val Val 305

Ser Val Leu Thr Val 310

Leu His Gln Asp Trp 315

Asn Gly Lys Glu Tyr

325

Lys Cys Lys Val Ser

330

Asn Lys Gly Leu Pro

335

Ser Ile Glu Lys Thr

340

Ile Ser Lys Ala Lys

345

Gly Gln Pro Arg Glu

350

Ala

Ser

Phe 160

Gly

Leu

Tyr

Arg

Gly 240

Thr

Val

Val

Ser

Leu 320

Ser

Pro

Gln

Gln Val Tyr Thr Leu

Pro Pro Ser Gln Glu

Glu Met Thr Lys Asn

- 479 044746

355

360

365

Val

Ser

370

Leu

Thr

Cys

Leu

Val

375

Lys

Gly

Phe

Tyr

Pro

380

Ser

Asp

Ile

Ala

Val

385

Glu

Trp

Glu

Ser

Asn

390

Gly

Gln

Pro

Glu

Asn

395

Asn

Tyr

Lys

Thr

Thr

400

Pro

Pro

Val

Leu

Asp

405

Ser

Asp

Gly

Ser

Phe

410

Phe

Leu

Tyr

Ser

Arg 415

Leu

Thr

Val

Asp

Lys 420

Ser

Arg

Trp

Gln

Glu

425

Gly

Asn

Val

Phe

Ser 430

Cys

Ser

Val

Met

His

435

Glu

Ala

Leu

His

Asn

440

His

Tyr

Thr

Gln

Lys

445

Ser

Leu

Ser

Leu Ser Leu Gly Lys

450 <210> 567 <211> 1341 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 567 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagtac atactacgca 180 gactccgtga aggggccgatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gactgagagc tgacgacacg gctgtctatt actgtgtgag agatccggtg 300 ggggcgctact actacggtat ggacgtctgg ggccaaggga ccacggtcac cgtctcctca 360 gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 420 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacgaagacc 600 tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 660 aaatatggtc ccccatgccc accgtgccca gcaccaggcg gtggcggacc atcagtcttc 720 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 780 gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 840

- 480 044746 gtggaggtgc gtggtcagcg aaggtctcca cagccccgag caggtcagcc gagagcaatg ggctccttct gtcttctcat tccctgtctc ataatgccaa tcctcaccgt acaaaggcct agccacaggt tgacctgcct ggcagccgga tcctctacag gctccg tgat tgggtaaatg gacaaagccg cctgcaccag cccgtcctcc gtacaccctg ggtcaaaggc gaacaactac caggctcacc gcatgaggct a cgggaggagc gactggctga atcgagaaaa cccccatccc ttctacccca aagaccacgc gtggacaaga ctgcacaacc agttcaacag acggcaagga ccatct ccaa aggaggat gcgacatcgc ctcccgtgct gcaggtggca actacacaca cacgtaccgt gtacaagtgc agccaaaggg gaccaagaac cgtggagtgg ggactccgac ggaggggaat gaagtccctc

900

960

1020

1080

1140

1200

1260

1320

1341 <210> 568 <211> 446 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>568

Glu Val 1

Gln Leu

Val Glu 5

Ser Leu

Arg Leu 20

Ser Cys

Tyr Met

Ser Trp 35

Val Arg

Ser Val

Ile Tyr

Ser Gly

Gly Arg 65

Phe Thr

Ile Ser

Gln Met

Asn Arg

Leu Arg 85

Arg Asp

Pro Val

100

Gly Arg

Gly Thr

Thr Val 115

Thr Val

Phe Pro

Leu Ala

Pro Cys

Ser Gly

Ala Ala

Gln Ala 40

Gly Ser 55

Arg Asp

Ala Asp

Tyr Tyr

Ser Ser

120

Ser Arg

Gly Gly 10

Ser Gly 25

Pro Gly

Thr Tyr

Asn Ser

Asp Thr

Tyr Gly 105

Ala Ser

Ser Thr

Leu Val

Phe Thr

Lys Gly

Tyr Ala 60

Lys Asn 75

Ala Val

Met Asp

Thr Lys

Ser Glu

Glin Pro

Val Ser

Leu Glu 45

Asp Ser

Gly Gly 15

Ser Asn

Trp Val

Val Lys

Thr Leu

Tyr Tyr

Val Trp

110

Gly Pro 125

Ser Thr

Tyr Leu 80

Cys Val 95

Gly Gln

Ser Val

Ala Ala

- 481 044746

130

135

140

Leu Gly Cys Leu Val 145

Lys Asp Tyr Phe Pro 150

Glu Pro Val Thr Val 155

Trp Asn Ser Gly Ala

165

Leu Thr Ser Gly Val

170

His Thr Phe Pro Ala

175

Leu Gln Ser Ser Gly

180

Leu Tyr Ser Leu Ser

185

Ser Val Val Thr Val

190

Ser Ser Ser Leu Gly 195

Thr Lys Thr Tyr Thr 200

Cys Asn Val Asp His

205

Pro Ser Asn Thr Lys

210

Val Asp Lys Arg Val

215

Glu Ser Lys Tyr Gly

220

Pro Cys Pro Pro Cys 225

Pro Ala Pro Gly Gly 230

Gly Gly Pro Ser Val 235

Leu Phe Pro Pro Lys

245

Pro Lys Asp Thr Leu

250

Met Ile Ser Arg Thr

255

Glu Val Thr Cys Val

260

Val Val Asp Val Ser

265

Gln Glu Asp Pro Glu

270

Gln Phe Asn Trp Tyr

275

Val Asp Gly Val Glu

280

Val His Asn Ala Lys

285

Lys Pro Arg Glu Glu

290

Gln Phe Asn Ser Thr

295

Tyr Arg Val Val Ser

300

Leu Thr Val Leu His 305

Gln Asp Trp Leu Asn 310

Gly Lys Glu Tyr Lys 315

Lys Val Ser Asn Lys

325

Gly Leu Pro Ser Ser

330

Ile Glu Lys Thr Ile

335

Lys Ala Lys Gly Gln

340

Pro Arg Glu Pro Gln

345

Val Tyr Thr Leu Pro

350

Ser Gln Glu Glu Met

355

Thr Lys Asn Gln Val

360

Ser Leu Thr Cys Leu

365

Lys Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val

375

Glu Trp Glu Ser Asn

380

Ser 160

Val

Pro

Lys

Pro

Phe 240

Pro

Val

Thr

Val

Cys 320

Ser

Pro

Val

Gly

- 482 044746

Gln 385 Pro Glu Asn Asn Tyr 390 Lys Thr Thr Pro Pro 395 Val Leu Asp Ser Asp 400 Gly Ser Phe Phe Leu 405 Tyr Ser Arg Leu Thr 410 Val Asp Lys Ser Arg 415 Trp Gln Glu Gly Asn 420 Val Phe Ser Cys Ser 425 Val Met His Glu Ala 430 Leu His Asn His Tyr 435 Thr Gln Lys Ser Leu 440 Ser Leu Ser Leu Gly 445 Lys

<210> 569 <211> 1332 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 569 gaggtgcagc tggtggagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtc atttatagcg gcggtagcac attctactca 180 gactccgtga aggggccgatt cagcatctcc agagacaatt ccaagaacac actgtatctt 240 caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agacctctac 300 tactacggta tggacgtctg gggccaaggg accacggtca ccgtctcctc agcctccacc 360 aagggcccat cggtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc 420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctacacctgc 600 aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt 660 ccccatgcc caccgtgccc agcaccaggc ggtggcggac catcagtctt cctgttcccc 720 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg 780 gacgtgagcc aggaagacc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 840 cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 900 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 960 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1020 gagccacagg tgtacaccct gcccccatcc caggagaga tgaccaagaa ccaggtcagc 1080 ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1140

- 483 044746 gggcagccgg ttcctctaca tgctccgtga ctgggtaaat agaacaacta gcaggctcac tgcatgaggc ga caagaccacg cgtggacaag tctgcacaac cctcccgtgc agcaggtggc cactacacac tggactccga aggaggggaa agaagtccct cggctccttc t gtcttctca ctccctgtct

1200

1260

1320

1332 <210> 570 <211> 443 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>570

Glu Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly

Leu Ile

Glin Pro

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Val Thr

Val Ser

Tyr Met

Ser Trp 35

Val Arg

Gln Ala

Pro Gly

Lys Gly

Leu Glu 45

Ser Val

Ile Tyr

Ser Gly

Gly Ser 55

Thr Phe

Tyr Ser 60

Asp Ser

Gly Gly 15

Ser Asn

Trp Val

Val Lys

Gly Arg 65

Phe Ser

Ile Ser

Arg Asp

Asn Ser

Lys Asn 75

Thr Leu

Tyr Leu 80

Gln Met

Asn Ser

Leu Arg 85

Ala Glu

Asp Thr

Ala Val

Tyr Tyr

Cys Ala 95

Arg Asp

Leu Tyr

100

Tyr Tyr

Gly Met

Asp Val 105

Trp Gly

Gln Gly

110

Thr Thr

Val Thr

Val Ser

115

Ser Ala

Ser Thr

120

Lys Gly

Pro Ser

Val Phe 125

ProLeu

Ala Pro

130

Cys Ser

Arg Ser

Thr Ser 135

Glu Ser

Thr Ala

140

Ala Leu

Gly Cys

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

145 150 155 160

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

165 170 175

- 484 044746

Ser

Leu

Thr

Pro 225

Pro

Cys

Trp

Glu

Leu 305

Asn

Gly

Glu

Tyr

Asn 385

Phe

Asn

Gly Leu Tyr

180

Gly Thr Lys

195

Lys Val Asp 210

Cys Pro Ala

Lys Pro Lys

Val Val Val

260

Tyr Val Asp

275

Glu Gln Phe 290

His Gln Asp

Lys Gly Leu

Gln Pro Arg

340

Met Thr Lys

355

Pro Ser Asp 370

Asn Tyr Lys

Leu Tyr Ser

Val Phe Ser

420

Ser Leu Ser

Thr Tyr Thr

Lys Arg Val

215

Pro Gly Gly

230

Asp Thr Leu 245

Asp Val Ser

Gly Val Glu

Asn Ser Thr

295

Trp Leu Asn

310

Pro Ser Ser 325

Glu Pro Gln

Asn Gln Val

Ile Ala Val

375

Thr Thr Pro

390

Arg Leu Thr 405

Cys Ser Val

Ser Val Val

185

Cys Asn Val 200

Glu Ser Lys

Gly Gly Pro

Met Ile Ser

250

Gln Glu Asp

265

Val His Asn 280

Tyr Arg Val

Gly Lys Glu

Ile Glu Lys

330

Val Tyr Thr

345

Ser Leu Thr 360

Glu Trp Glu

Pro Val Leu

Val Asp Lys

410

Met His Glu

425

Thr Val Pro

Ser Ser Ser 190

Asp His Lys

205

Pro Ser Asn

Tyr Gly Pro

220

Ser Val Phe 235

Arg Thr Pro

Pro Glu Val

Ala Lys Thr

285

Val Ser Val

300

Tyr Lys Cys 315

Thr Ile Ser

Leu Pro Pro

Cys Leu Val

365

Ser Asn Gly

380

Asp Ser Asp 395

Ser Arg Trp

Ala Leu His

Pro Cys Pro

Leu Phe Pro

240

Glu Val Thr

255

Gln Phe Asn 270

Lys Pro Arg

Leu Thr Val

Lys Val Ser

320

Lys Ala Lys

335

Ser Gln Glu 350

Lys Gly Phe

Gln Pro Glu

Gly Ser Phe

400

Gln Glu Gly 415

Asn His Tyr 430

- 485 044746

Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435

440 <210> 571 <211> 1350 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 571 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttcagc agctatgcta tcacctggggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaagg atcatcccta tgtttggtat agcaaactac 180 gcacagaagt tccaggggcag agtcacgatt accgcggaca aatccacgag cacagcctac 240 atggaggtga gcagcctgag atctgaggac acggccgtgt attackgtgc gagaacaccg 300 ttttactatg atagtagtgg ttattacctt gactactgggg gccagggaac cctggtcacc 360 gtctcctcag cctccaccaa gggcccatcg gtcttccccc tggcgccctg ctccaggagc 420 acctccgaga gcacagccgc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 480 acggtgtcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 540 cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttggggc 600 acgaagacct acacctgcaa cgtagatcac aagccagca acaccaaggt ggacaagaga 660 gttgagtcca aatatggtcc cccatgccca ccgtgcccag caccaggcgg tggcggacca 720 tcagtcttcc tgttcccccc aaaacccaag gacactctca tgatctcccg gacccctgag 780 gtcacgtgcg tggtggtgga cgtgagccag gaagaccccg aggtccagtt caactggtac 840 gtggatggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gttcaacagc 900 acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa cggcaagggag 960 tacaagtgca aggtctccaa caaaggcctc ccgtcctcca tcgagaaaac catctccaaa 1020 gccaaagggc agccccgaga gccacaggtg tacaccctgc ccccatccca ggagaggagatg 1080 accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctaccccag cgacatcgcc 1140 gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200 gactccgacg gctccttctt ccctacagc aggctcaccg tggacaagag caggtggcag 1260 gaggggaatg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacacag 1320 aagtccctct ccctgtctct gggtaaatga 1350

<210> 572 <211> 449

- 486 044746 <212> PROTEIN <213> Artificial <220>

<223> Synthetic <400> 572

Gln Val Gln Leu Val 1 5 sequence

Gln Ser Gly Ala Glu 10

Val Lys Lys Pro Gly

Ser Val Lys Val Ser

Cys Lys Ala Ser Gly

Gly Thr Phe Ser Ser 30

Ala Ile Thr Trp Val 35

Arg Gln Ala Pro Gly 40

Gln Gly Leu Glu Trp 45

Gly Arg Ile Ile Pro 50

Met Phe Gly Ile Ala 55

Asn Tyr Ala Gln Lys 60

Gln Gly Arg Val Thr 65

Ile Thr Ala Asp Lys 70

Ser Thr Ser Thr Ala 75

Met Glu Val Ser

Leu Arg Ser Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Arg Thr Pro Phe

100

Tyr Tyr Asp Ser Ser

105

Gly Tyr Tyr Leu Asp

110

Trp Gly Gln Gly Thr 115

Leu Val Thr Val Ser

120

Ser Ala Ser Thr Lys

125

Pro Ser Val Phe Pro

130

Leu Ala Pro Cys Ser

135

Arg Ser Thr Ser Glu 140

Thr Ala Ala Leu Gly 145

Cys Leu Val Lys Asp 150

Tyr Phe Pro Glu Pro 155

Thr Val Ser Trp Asn

165

Ser Gly Ala Leu Thr

170

Ser Gly Val His Thr

175

Pro Ala Val Leu Gln

180

Ser Ser Gly Leu Tyr

185

Ser Leu Ser Ser Val

190

Thr Val Pro Ser Ser

195

Ser Leu Gly Thr Lys

200

Thr Tyr Thr Cys Asn

205

Asp His Lys Pro Ser 210

Asn Thr Lys Val Asp 215

Lys Arg Val Glu Ser

220

Ser

Tyr

Met

Phe

Tyr 80

Cys

Tyr

Gly

Ser

Val 160

Phe

Val

Val

Lys

- 487 044746

Tyr Gly Pro 225

Ser Val Phe

Pro Cys Pro

230

Leu Phe Pro

245

Arg Thr Pro

Glu Val Thr 260

Pro Glu Val

275

Gln Phe Asn

Pro Cys Pro Ala Pro Gly 235

Pro Lys Pro Lys Asp Thr 250

Cys Val Val Val Asp Val 265

Trp Tyr Val Asp Gly Val 280

Gly Gly Gly

Leu Met Ile

255

Ser Gln Glu

270

Glu Val His 285

Ala Lys Thr 290

Lys Pro Arg Glu Glu

295

Gln Phe Asn Ser Thr Tyr Arg 300

Val Ser Val 305

Leu Thr Val Leu His

310

Gln Asp Trp Leu Asn Gly Lys 315

Tyr Lys Cys

Lys Val Ser Asn Lys

325

Gly Leu Pro Ser Ser Ile Glu

330 335

Thr Ile Ser

Leu Pro Pro

355

Lys Ala Lys 340

Ser Gln Glu

Gly Gln Pro Arg Glu Pro Gln Val Tyr

345 350

Glu Met Thr Lys Asn Gln Val Ser Leu

360 365

Cys Leu Val

370

Lys Gly Phe

Tyr Pro Ser Asp Ile Ala Val Glu Trp

375 380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr

385 390

Lys Thr Thr

395

Pro Pro Val

Asp Ser Asp Gly Ser Phe Phe Leu Tyr 405

Ser Arg Leu 410

Thr Val Asp

415

Ser Arg Trp Gln Glu Gly Asn Val Phe

420 425

Ser Cys Ser

Val Met His

430

Ala Leu His Asn His Tyr Thr Gln Lys

435 440

Ser Leu Ser

Leu Ser Leu 445

Pro 240

Ser

Asp

Asn

Val

Glu 320

Lys

Thr

Thr

Glu

Leu 400

Lys

Glu

Gly

Lys <210> 573 <211> 357

- 488 044746 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 573

gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggct caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg gactggagtg ggtctcagtt atttatagcg gaggtaccac atactacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtctctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgcg aggggagggg 300 gccaactact acggtatgga cgtctggggc caagggacca cggtcaccgt ctcctca 357

<210> 574 <211> 119 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>574

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Leu Thr 25

Val Ser Ser Asn

Tyr Met Ser Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Ser Val Ile Tyr 50

Ser Gly Gly Thr 55

Thr Tyr Tyr Ala 60

Asp Ser Val Lys

Gly Arg Phe Thr 65

Ile Ser Arg His 70

Asn Ser Lys Asn 75

Thr Leu Ser Leu

Gln Met Asn Ser

Leu Arg Ala Glu 85

Asp Thr Ala Val 90

Tyr Tyr Cys Ala 95

Arg Gly Glu Gly

100

Ala Asn Tyr Tyr

Gly Met Asp Val 105

Trp Gly Gln Gly

110

Thr Thr Val Thr

115

Val Ser Ser <210> 575

- 489 044746 <211> 21 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>575 atttatagcg gaggtaccac a <210>576 <211>7 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>576

Ile Tyr Ser Gly Gly Thr Thr <210>577 <211>39 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>577 gcgcgagggg aggggggccaa ctactacggt atggacgtc <210>578 <211>13 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>578

Ala Arg Gly Glu Gly Ala Asn Tyr Tyr Gly Met Asp Val

510 <210>579 <211>336 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 579 cagtctgtgc tgacgcagcc tcctgcactg ggagcagctc gccctcagtg tctggggccc caacatcggg acaggttatg cagggcagag ggtcaccatc atgtacactg gtaccagcag

120

- 490 044746

cttccaggaa cagcccccaa actcctcatc tatggtaaca gcaatcggcc ctcaggggtc 180 cctgaccgat tctctggctc caagtctggc acctcagcct ccctggccat cactgggctc 240 caggctgagg atgaggctga ttattactgc cagtcctatg acagcagcct gagtggttat 300 gtggtattcg gcggagggac caagctgacc gtccta 336

<210> 580 <211> 112 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 580

Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly Gln

5 10 15

Arg Val Thr Ile Ser Cys Thr Gly 20

Ser Ser Ser Asn Ile Gly Thr Gly 25 30

Tyr Asp Val His Trp Tyr Gln Gln

40

Leu Pro Gly Thr Ala Pro Lys Leu 45

Leu Ile Tyr Gly Asn Ser Asn Arg

55

Pro Ser Gly Val Pro Asp Arg Phe 60

Ser Gly Ser Lys Ser Gly Thr Ser 65 70

Ala Ser Leu Ala Ile Thr Gly Leu

80

Gln Ala Glu Asp Glu Ala Asp Tyr 85

Tyr Cys Gln Ser Tyr Asp Ser Ser

95

Leu Ser Gly Tyr Val Val Phe Gly

100

Gly Gly Thr Lys Leu Thr Val Leu

105 110 <210> 581 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>581 agctccaaca tcgggacagg ttatgat <210>582 <211>9 <212> PROTEIN

- 491 044746 <213>

Artificial sequence <220>

<223>

Synthetic <400>

582

Ser Ser Asn Ile Gly Thr Gly Tyr Asp <210> 583 <211> 9 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>583 ggtaacagc9 <210>584 <211>3 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>584

Gly Asn Ser 1 < 210 > 585 < 211 > 36 < 212 > DNA < 213 > Artificial sequence < 220 >

<223> Synthetic <400>585 cagtcctatg acagcagcct gagtggttat gtggta36 <210>586 <211>12 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>586

Gln Ser Tyr Asp Ser Ser Leu Ser Gly Tyr Val Val

5 10

- 492 044746 <210> 587 <211> 1350 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 587

gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggct caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg gactggagtg ggtctcagtt atttatagcg gaggtaccac atactacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtctctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgcg aggggagggg 300 gccaactact acggtatgga cgtctggggc caagggacca cggtcaccgt ctcctcagcc 360 tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctggggggc 420 acaggccc tggggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac ccagacctac 600 atctgcaacg tgaatcacaa gccagcaac accaaggtgg acaagaaagt tgagcccaaa 660 tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720 tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780 gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840 gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900 acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaagggag 960 tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020 gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080 accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140 gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200 gactccgacg gctccttctt ccctacagc aagctcaccg tggacaagag caggtggcag 1260 caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320 aagtccctct ccctgtctcc gggtaaatga 1350

<210> 588 <211> 449 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic

- 493 044746 <400> 588

Glu Val Gln Leu Val

5

Glu Ser Gly Gly Gly

Leu Val Gln Pro Gly

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Leu Thr Val Ser Ser

Tyr Met Ser Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Ser Val Ile Tyr Ser 50

Gly Gly Thr Thr Tyr 55

Tyr Ala Asp Ser Val 60

Gly Arg Phe Thr Ile 65

Ser Arg His Asn Ser 70

Lys Asn Thr Leu Ser 75

Gln Met Asn Ser Leu

Arg Ala Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Gly Glu Gly Ala

100

Asn Tyr Tyr Gly Met

105

Asp Val Trp Gly Gln

110

Thr Thr Val Thr Val

115

Ser Ser Ala Ser Thr

120

Lys Gly Pro Ser Val 125

Pro Leu Ala Pro Ser

130

Ser Lys Ser Thr Ser 135

Gly Gly Thr Ala Ala 140

Gly Cys Leu Val Lys 145

Asp Tyr Phe Pro Glu 150

Pro Val Thr Val Ser 155

Asn Ser Gly Ala Leu

165

Thr Ser Gly Val His

170

Thr Phe Pro Ala Val

175

Gln Ser Ser Gly Leu

180

Tyr Ser Leu Ser Ser

185

Val Val Thr Val Pro

190

Ser Ser Leu Gly Thr

195

Gln Thr Tyr Ile Cys 200

Asn Val Asn His Lys 205

Ser Asn Thr Lys Val

210

Asp Lys Lys Val Glu

215

Pro Lys Ser Cys Asp 220

Thr His Thr Cys Pro 225

Pro Cys Pro Ala Pro 230

Glu Leu Leu Gly Gly 235

Gly

Asn

Val

Lys

Leu 80

Ala

Gly

Phe

Leu

Trp 160

Leu

Ser

Pro

Lys

Pro 240

- 494 044746

Ser Val Phe

Leu Phe Pro

245

Pro Lys Pro

Lys Asp Thr 250

Leu Met Ile

255

Arg Thr Pro

Glu Val Thr 260

Cys Val Val

265

Val Asp Val

Ser His Glu

270

Pro Glu Val

275

Lys Phe Asn

Trp Tyr Val

280

Asp Gly Val

Glu Val His 285

Ala Lys Thr 290

Lys Pro Arg

Glu Glu Gln 295

Tyr Asn Ser

300

Thr Tyr Arg

Val Ser Val 305

Leu Thr Val

310

Leu His Gln

Asp Trp Leu

315

Asn Gly Lys

Tyr Lys Cys

Lys Val Ser

325

Asn Lys Ala

Leu Pro Ala 330

Pro Ile Glu

335

Thr Ile Ser

Lys Ala Lys 340

Gly Gln Pro

345

Arg Glu Pro

Gln Val Tyr

350

Leu Pro Pro

355

Ser Arg Asp

Glu Leu Thr

360

Lys Asn Gln

Val Ser Leu 365

Cys Leu Val

370

Lys Gly Phe

Tyr Pro Ser 375

Asp Ile Ala

380

Val Glu Trp

Ser Asn Gly 385

Gln Pro Glu

390

Asn Asn Tyr

Lys Thr Thr

395

Pro Pro Val

Asp Ser Asp

Gly Ser Phe

405

Phe Leu Tyr

Ser Lys Leu 410

Thr Val Asp

415

Ser Arg Trp

Gln Gln Gly 420

Asn Val Phe

425

Ser Cys Ser

Val Met His

430

Ala Leu His

435

Asn His Tyr

Thr Gln Lys

440

Ser Leu Ser

Leu Ser Pro 445

Ser

Asp

Asn

Val

Glu 320

Lys

Thr

Thr

Glu

Leu 400

Lys

Glu

Gly

Lys <210> 589 <211> 657 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

- 495 044746

<400> 589 cagtctgtgc tgacgcagcc gccctcagtg tctggggccc cagggcagag ggtcaccatc 60 tcctgcactg ggagcagctc caacatcgggg acaggttatg atgtacactg gtaccagcag 120 cttccaggaa cagcccccaa actcctcatc tatggtaaca gcaatcggcc ctcaggggtc 180 cctgaccgat tctctggctc caagtctggc acctcagcct ccctggccat cactgggctc 240 caggctgagg atgaggctga ttattactgc cagtcctatg acagcagcct gagtggttat 300 gtggtattcg gcggagggac caagctgacc gtcctaggcc agcccaaggc cgccccctcc 360 gtgaccctgt tccccccctc ctccgaggag ctgcaggcca acaaggccac cctggtgtgc 420 ctgatctccg acttctacc cggcgccgtg accgtggcct ggaaggccga ctcctccccc 480 gtgaaggccg gcgtggagac caccaccccc tccaagcagt ccaacaacaa gtacgccgcc 540 tcctcctacc tgtccctgac ccccgagcag tggaagtccc accggtccta ctcctgccag 600 gtgaccacg aggggctccac cgtggagaag accgtggccc ccaccgagtg ctcctga 657

<210> 590 <211> 218 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 590

Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly Gln

5 10 15

Arg Val Thr Ile Ser Cys Thr Gly 20

Ser Ser Ser Asn Ile Gly Thr Gly 25 30

Tyr Asp Val His Trp Tyr Gln Gln

40

Leu Pro Gly Thr Ala Pro Lys Leu 45

Leu Ile Tyr Gly Asn Ser Asn Arg

55

Pro Ser Gly Val Pro Asp Arg Phe 60

Ser Gly Ser Lys Ser Gly Thr Ser 65 70

Ala Ser Leu Ala Ile Thr Gly Leu

80

Gln Ala Glu Asp Glu Ala Asp Tyr 85

Tyr Cys Gln Ser Tyr Asp Ser Ser

95

Leu Ser Gly Tyr Val Val Phe Gly

100

Gly Gly Thr Lys Leu Thr Val Leu

105 110

- 496 044746

Gly Gln Pro Lys Ala Ala Pro Ser

115 120

Val Thr Leu Phe Pro Pro Ser Ser

125

Glu Glu Leu Gln Ala Asn Lys Ala

130 135

Thr Leu Val Cys Leu Ile Ser Asp

140

Phe Tyr Pro Gly Ala Val Thr Val

145 150

Ala Trp Lys Ala Asp Ser Ser Pro

155 160

Val Lys Ala Gly Val Glu Thr Thr

165

Thr Pro Ser Lys Gln Ser Asn Asn

170 175

Lys Tyr Ala Ala Ser Ser Tyr Leu 180

Ser Leu Thr Pro Glu Gln Trp Lys

185 190

Ser His Arg Ser Tyr Ser Cys Gln

195 200

Val Thr His Glu Gly Ser Thr Val

205

Glu Lys Thr Val Ala Pro Thr Glu

210215

Cys Ser <210>591 <211>1338 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 591 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggct caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg gactggagtg ggtctcagtt atttatagcg gaggtaccac atactacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtctctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgcg aggggagggg 300 gccaactact acggtatgga cgtctggggc caagggacca cggtcaccgt ctcctcagcc 360 tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc 420 acagccgccc tggggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac gaagacctac 600 acctgcaacg tagatcacaa gccagcaac accaaggtgg acaagagt tgagtccaaa 660 tatggtcccc catgcccacc gtgccagca ccaggcggtg gcggaccatc agtcttcctg 720 ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 780

- 497 044746

gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 840 gaggtgcata atgccaagac aaagccgcgg gagggagt tcaacagcac gtaccgtgtg 900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaagggagta caagtgcaag 960 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1020 ccccgagagc cacaggtgta caccctgccc ccaccagg aggagatgac caagaaccag 1080 gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtggggag 1140 agcaatggggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200 tccttcttcc tctacagcag gctcaccgtg gacaagagca ggtggcagga ggggaatgtc 1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gtccctctcc 1320 ctgtctctgg gtaaatga 1338

<210> 592 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 592

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25

Tyr Met Ser Trp Val Arg Gln Ala Pro 35 40

Gly Leu Thr Val Ser Ser Asn 30

Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr 50

Gly Arg Phe Thr 65

Ser Gly Gly Thr Thr Tyr Tyr Ala Asp Ser Val Lys 55 60

Ile Ser Arg His Asn Ser Lys Asn Thr Leu Ser Leu 70 75 80

Gln Met Asn

Ser Leu Arg Ala Glu Asp Thr Ala Val

90

Tyr Tyr Cys Ala 95

Arg Gly Glu Gly Ala Asn Tyr Tyr 100

Thr Thr Val Thr Val Ser Ser Ala

115 120

Gly Met Asp Val Trp Gly Gln Gly

105 110

Ser Thr Lys Gly Pro Ser Val Phe

125

- 498 044746

Pro

Gly 145

Asn

Gln

Ser

Ser

Cys 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Gln

Gly

Leu Ala Pro 130

Cys Leu Val

Ser Gly Ala

Ser Ser Gly

180

Ser Leu Gly

195

Asn Thr Lys 210

Pro Pro Cys

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Lys Gly Gln

340

Glu Glu Met

355

Phe Tyr Pro 370

Cys Ser Arg

135

Lys Asp Tyr

150

Leu Thr Ser 165

Leu Tyr Ser

Thr Lys Thr

Val Asp Lys

215

Pro Ala Pro

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Gln Phe Asn

295

Gln Asp Trp

310

Gly Leu Pro 325

Pro Arg Glu

Thr Lys Asn

Ser Asp Ile

375

Ser Thr Ser

Phe Pro Glu

Gly Val His

170

Leu Ser Ser

185

Tyr Thr Cys 200

Arg Val Glu

Gly Gly Gly

Thr Leu Met

250

Val Ser Gln

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ser Ser Ile 330

Pro Gln Val 345

Gln Val Ser 360

Ala Val Glu

Glu Ser Thr

140

Pro Val Thr 155

Thr Phe Pro

Val Val Thr

Asn Val Asp

205

Ser Lys Tyr

220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Tyr Thr Leu

Leu Thr Cys

365

Trp Glu Ser

380

Ala Ala Leu

Val Ser Trp

160

Ala Val Leu

175

Val Pro Ser 190

His Lys Pro

Gly Pro Pro

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Gln 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

Pro Pro Ser 350

Leu Val Lys

Asn Gly Gln

- 499 044746

Pro 385 Glu Asn Asn Tyr Lys 390 Thr Thr Pro Pro Val 395 Leu Asp Ser Asp Gly 400 Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln 405 410 415 Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn 420 425 430 His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys 435 440 445

<210> 593 <211> 357 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 593 gaggtgcagc tcctgtgcag ccagggaagg gactccgtta caaatgaaca gggatcccct tggtggagtc cctctggact ggctggagtg agggccgatt gcctgagact acggtatgga tgggggaggc caccgtcaat ggtctcactt caccatctcc tgaggac acg cgtctggggc ttggtccagc cgcaactaca atttatagcg agagacaatt gctgtgtatt caagggacca ctggggggtc tgagctgggt gtggtagcac ccaagaacac actgtgcgag cggtcaccgt cctgagactc ccgccaggct atactacgca gctgtatctt aggtgaactg ctcctca

120

180

240

300

357 <210> 594 <211> 119 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 594

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Leu Thr 25

Val Asn Arg Asn 30

Tyr Met Ser Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Ser Leu Ile Tyr 50

Ser Gly Gly Ser 55

Thr Tyr Tyr Ala 60

Asp Ser Val Lys

- 500 044746

Gly Arg Phe Thr 65

Ile Ser Arg Asp 70

Asn Ser Lys Asn 75

Thr Leu Tyr Leu 80

Gln Met Asn Ser

Leu Arg Leu Glu 85

Asp Thr Ala Val 90

Tyr Tyr Cys Ala 95

Arg Gly Glu Leu

100

Gly Ile Pro Tyr

Gly Met Asp Val 105

Trp Gly Gln Gly 110

Thr Thr Val Thr

115

Val Ser Ser <210> 595 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>595 ggactcaccg tcaatcgcaa ctac <210>596 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>596

Gly Leu Thr Val Asn Arg Asn Tyr <210>597 <211>39 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>597 gcgagaggtg aactggggat cccctacggt atggacgtc <210>598 <211>13 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic

- 501 044746 <400>598

Ala Arg Gly Glu Leu Gly Ile Pro Tyr Gly Met Asp Val 1 510 <210>599 <211>330 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic < 400>599 cagtctgtgt tgacgcagcc gccctcagtg tctgcggccc caggacagaa ggtcaccatc60 tcctgctctg gaagcagctc caacattggg aataattatg tatcctggta ccagcagctc120 ccaggaacag cccccaaact cctcatttat gacaata ata agcgaccctc agggattcct180 gaccgcttct ctggctccaa gtctggcacg tcagccaccc tgggcatcac cggactccag240 actggggacg aggccgatta ttactgcgga acatgggata gcagcctgag tgctggggtg300 ttcggcggag ggaccaagct gaccgtccta330 < 210> 600 < 211>110 < 212> PROTEIN < 213> Artificial sequence <220>

<223> Synthetic <400>600

Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Ala Ala Pro Gly Gln

5 1015

Lys Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Asn Asn 20 2530

Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 4045

Ile Tyr Asp Asn Asn Lys Arg Pro Ser Gly Ile Pro Asp Arg Phe Ser 50 5560

Gly Ser Lys Ser Gly Thr Ser Ala Thr Leu Gly Ile Thr Gly Leu Gln 65 70 7580

Thr Gly Asp Glu Ala Asp Tyr Tyr Cys Gly Thr Trp Asp Ser Ser Leu 85 9095

- 502 044746

Ser Ala Gly Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105110 <210>601 <211>33 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>601 ggaacatggg atagcagcct gagtgctggg gtg <210>602 <211>11 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>602

Gly Thr Trp Asp Ser Ser Leu Ser Ala Gly Val

510 <210>603 <211>1350 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 603 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggact caccgtcaat cgcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcactt atttatagcg gtggtagcac atactacgca 180 gactccgtta aggggccgatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagact tgaggacacg gctgtgtatt actgtgcgag aggtgaactg 300 ggggatcccct acggtatgga cgtctggggc caagggacca cggtcaccgt ctcctcagcc 360 tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctggggggc 420 acaggccc tggggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac ccagacctac 600 atctgcaacg tgaatcacaa gccagcaac accaaggtgg acaagaaagt tgagcccaaa 660 tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720

- 503 044746

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780 gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840 gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900 acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaagggag 960 tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020 gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080 accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140 gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200 gactccgacg gctccttctt ccctacagc aagctcaccg tggacaagag caggtggcag 1260 caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320 aagtccctct ccctgtctcc gggtaaatga 1350

<210> 604 <211> 449 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>604

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Leu Thr Val Asn Arg Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Leu Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Ser Leu Arg Leu Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

Arg Gly Glu Leu Gly Ile Pro Tyr Gly Met Asp Val Trp Gly Gln Gly

100 105110

Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe

115 120125

- 504 044746

Pro

Gly 145

Asn

Gln

Ser

Ser

Thr 225

Ser

Arg

Pro

Ala

Val 305

Tyr

Thr

Leu

Cys

Leu Ala Pro 130

Cys Leu Val

Ser Gly Ala

Ser Ser Gly

180

Ser Leu Gly

195

Asn Thr Lys 210

His Thr Cys

Val Phe Leu

Thr Pro Glu

260

Glu Val Lys

275

Lys Thr Lys 290

Ser Val Leu

Lys Cys Lys

Ile Ser Lys

340

Pro Pro Ser

355

Leu Val Lys

Ser Ser Lys

135

Lys Asp Tyr

150

Leu Thr Ser 165

Leu Tyr Ser

Thr Gln Thr

Val Asp Lys

215

Pro Pro Cys

230

Phe Pro Pro 245

Val Thr Cys

Phe Asn Trp

Pro Arg Glu

295

Thr Val Leu

310

Val Ser Asn 325

Ala Lys Gly

Arg Asp Glu

Gly Phe Tyr

Ser Thr Ser

Phe Pro Glu

Gly Val His 170

Leu Ser Ser 185

Tyr Ile Cys 200

Lys Val Glu

Pro Ala Pro

Lys Pro Lys

250

Val Val Val

265

Tyr Val Asp 280

Glu Gln Tyr

His Gln Asp

Lys Ala Leu

330

Gln Pro Arg

345

Leu Thr Lys 360

Pro Ser Asp

Gly Gly Thr

140

Pro Val Thr 155

Thr Phe Pro

Val Val Thr

Asn Val Asn

205

Pro Lys Ser

220

Glu Leu Leu 235

Asp Thr Leu

Asp Val Ser

Gly Val Glu

285

Asn Ser Thr

300

Trp Leu Asn 315

Pro Ala Pro

Glu Pro Gln

Asn Gln Val

365

Ile Ala Val

Ala Ala Leu

Val Ser Trp

160

Ala Val Leu

175

Val Pro Ser 190

His Lys Pro

Cys Asp Lys

Gly Gly Pro

240

Met Ile Ser

255

His Glu Asp 270

Val His Asn

Tyr Arg Val

Gly Lys Glu

320

Ile Glu Lys

335

Val Tyr Thr 350

Ser Leu Thr

Glu Trp Glu

- 505 044746

370

375

380

Ser Asn Gly Gln Pro Glu Asn Asn Tyr

385 390

Lys Thr Thr Pro Pro Val Leu

395 400

Asp Ser Asp Gly Ser Phe Phe Leu Tyr 405

Ser Lys Leu Thr Val Asp Lys

410 415

Ser Arg Trp Gln Gln Gly Asn Val Phe

420 425

Ser Cys Ser Val Met His Glu 430

Ala Leu His Asn His Tyr Thr Gln Lys

435 440

Ser Leu Ser Leu Ser Pro Gly 445

Lys <210> 605 <211> 651 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 605 cagtctgtgt tcctgctctg ccaggaacag gaccgcttct actggggacg ttcggcggag ctgttccccc tccgacttct gccggcgtgg tacctgtccc cacgagggct tgacgcagcc gaagcagctc cccccaaact ctggctccaa aggccgatta g gaccaagct cctcctccga accccggcgc agaccaccac tgaccccga ccaccgtgga gccctcagtg caacattggg cctcatttat gtctggcacg ttactgcgga gaccgtccta ggagctgcag cgtgaccgtg cccctccaag gcagtggaag gaagaccgtg tctgcggccc aataattatg gacaata ata tcagccaccc acatgggata ggccagccca gccaacaagg gcctggaagg cagtccaaca tcccaccggt gcccccaccg caggacagaa tatcctggta agcgaccctc tgggcatcac gcagcctgag aggccgcccc ccaccctggt ccgactcctc acaagtacgc cctactcctg agtgctcctg ggtcaccatc ccagcagctc agggattcct cggactccag tgctggggtg ctccgtgacc gtgcctgatc ccccgtgaag cgcctcctcc ccaggtgacc a

120

180

240

300

360

420

480

540

600

651 <210> 606 <211> 216 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic

- 506 044746 <400> 606

Gln Ser Val Leu Thr

5

Lys Val Thr Ile Ser 20

Gln Pro Pro Ser Val

Cys Ser Gly Ser Ser 25

Ser Ala Ala Pro Gly

Ser Asn Ile Gly Asn 30

Tyr Val Ser Trp Tyr 35

Gln Gln Leu Pro Gly 40

Thr Ala Pro Lys Leu 45

Ile Tyr Asp Asn Asn 50

Lys Arg Pro Ser Gly 55

Ile Pro Asp Arg Phe 60

Gly Ser Lys Ser Gly 65

Thr Ser Ala Thr Leu 70

Gly Ile Thr Gly Leu 75

Thr Gly Asp Glu Ala 85

Asp Tyr Tyr Cys Gly 90

Thr Trp Asp Ser Ser 95

Ser Ala Gly Val Phe

100

Gly Gly Gly Thr Lys

105

Leu Thr Val Leu Gly

110

Pro Lys Ala Ala Pro 115

Ser Val Thr Leu Phe

120

Pro Pro Ser Ser Glu

125

Leu Gln Ala Asn Lys

130

Ala Thr Leu Val Cys

135

Leu Ile Ser Asp Phe

140

Pro Gly Ala Val Thr 145

Val Ala Trp Lys Ala 150

Asp Ser Ser Pro Val 155

Ala Gly Val Glu Thr

165

Thr Thr Pro Ser Lys

170

Gln Ser Asn Asn Lys

175

Ala Ala Ser Ser Tyr

180

Leu Ser Leu Thr Pro

185

Glu Gln Trp Lys Ser

190

Arg Ser Tyr Ser Cys 195

Gln Val Thr His Glu

200

Gly Ser Thr Val Glu

205

Gln

Asn

Leu

Ser

Gln 80

Leu

Gln

Glu

Tyr

Lys 160

Tyr

His

Lys

Thr Val Ala Pro Thr Glu Cys Ser

210 215 <210> 607 <211> 384 <212> DNA <213> Artificial sequence

- 507 044746 <220>

<223> Synthetic <400> 607 gaagtgcagc tcctgtgcag ccagggaagg gcggactctg ctgcaaatga gagagatggg gggaccacgg tggtggagtc cctctggatt gcctggagtg tgaagggccg gcagtctgag atagtgtagt tcaccgtctc tgggggaggc caccttgat ggtctcaggt attcaccatc agctgaggac agtaccatct ctca ttggtacagc gattatgcca attagttgga tccagagaca acggccttgt gctaggaacg ctggcaggtc tgcactgggt ataggggtag acgccaagaa attactgcgc gtatggacgt cctgagactc ccggcaagct cataggctat ctccctg tat aaaagatggc ctggggccaa

120

180

240

300

360

384 <210> 608 <211> 128 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 608

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Asp Asp Tyr 25 30

Ala Met His Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Gly Ile Ser Trp Asn Arg Gly

55

Ser Ile Gly Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ala Lys Asn Ser Leu Tyr

80

Leu Gln Met Ser Ser Leu Arg Ala 85

Glu Asp Thr Ala Leu Tyr Tyr Cys

95

Ala Lys Asp Gly Glu Arg Trp Asp

100

Ser Val Val Val Pro Ser Ala Arg

105 110

Asn Gly Met Asp Val Trp Gly Gln

115 120

Gly Thr Thr Val Thr Val Ser Ser

125 <210> 609 <211> 24

- 508 044746 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>609 attagttgga ataggggtag cata <210>610 <211>8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>610

Ile Ser Trp Asn Arg Gly Ser Ile <210>611 <211>63 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>611 gcaaaagatg gcgagagatg ggatagtgta gtagtaccat ctgctaggaa cggtatggac gtc <210>612 <211>21 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>612

Ala Lys Asp Gly Glu Arg Trp Asp Ser Val Val Val Pro Ser Ala Arg

5 1015

Asn Gly Met Asp Val <210>613 <211>336 <212> DNA <213> Artificial Sequence <220>

<223> Synthetic

- 509 044746 <400> 613 cagtctgtgc tcctgcactg cttccaggaa cctgaccgat caggctgagg tatgtcttcg tgacgcagcc ggagcagctc cagcccccaa tctctggctc atgaggctga gaactgggac gccctcagtg caacatcggg actcctcatc caagtctgg c ttattactgc caaggtcacc tctggggccc gcaggttatg tatggtaaca acctcagcct cagtcctatg gtccta cagggcagag atgtacattg gcaatcggcc ccctggccat acagcagcct ggtcaccatc gtaccagcag ctcaggggtc cactgggctc gagtggctct

120

180

240

300

336 <210> 614 <211> 112 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 614

Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly Gln

5 10 15

Arg Val Thr Ile Ser Cys Thr Gly 20

Ser Ser Ser Asn Ile Gly Ala Gly 25 30

Tyr Asp Val His Trp Tyr Gln Gln

40

Leu Pro Gly Thr Ala Pro Lys Leu 45

Leu Ile Tyr Gly Asn Ser Asn Arg

55

Pro Ser Gly Val Pro Asp Arg Phe 60

Ser Gly Ser Lys Ser Gly Thr Ser 65 70

Ala Ser Leu Ala Ile Thr Gly Leu

80

Gln Ala Glu Asp Glu Ala Asp Tyr 85

Tyr Cys Gln Ser Tyr Asp Ser Ser

95

Leu Ser Gly Ser Tyr Val Phe Gly

100

Thr Gly Thr Lys Val Thr Val Leu

105 110 <210> 615 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 615 agctccaaca tcggggcagg ttatgat

- 510 044746 <210> 616 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>616

Ser Ser Asn Ile Gly Ala Gly Tyr Asp <210>617 <211>36 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>617 cagtcctatg acagcagcct gagtggctct tatgtc <210>618 <211>12 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>618

Gln Ser Tyr Asp Ser Ser Leu Ser Gly Ser Tyr Val 1 510 <210>619 <211>1377 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 619 gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct ccagggaagg gcctggagtg ggtctcaggt attagttgg a ataggggtag cataggctat gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat ctgcaaatga gcagtctgag agctgaggac acggccttgt attactgcgc aaaagatggc gagagatggg atagtgtagt agtaccatct gctaggaacg gtatggacgt ctggggcca a

120

180

240

300

360

- 511 044746

gggaccacgg tcaccgtctc ctcagcctcc accaagggcc catcggtctt ccccctggca 420 ccctcctcca agagcacctc tggggggcaca gcggccctgg gctgcctggt caaggactac 480 ttccccgaac cggtgacggt gtcgtggaac tcaggcgccc tgaccagcgg cgtgcacacc 540 ttcccggctg tcctacagtc ctcaggactc tactccctca gcagcgtggt gaccgtgccc 600 tccagcagct tggggcacca gacctacatc tgcaacgtga atcacaagcc cagcaacacc 660 aaggtggac agaaagttga gcccaaatct tgtgacaaaa ctcacacatg cccaccgtgc 720 ccagcacctg aactcctgggg gggaccgtca gtcttcctct tccccccaaa acccaaggac 780 accctcatga tctcccggac ccctgaggtc acatgcgtgg tggtggacgt gagccacgaa 840 gaccctgagg tcaagttcaa ctggtacgtg gacggcgtgg aggtgcataa tgccaagaca 900 aagccgcggg aggagcagta caacagcacg taccgtgtgg tcagcgtcct caccgtcctg 960 caccaggact ggctgaatgg caaggagtac aagtgcaagg tctccaacaa agccctccca 1020 gcccccatcg agaaaaccat ctccaaagcc aaagggcagc cccgagaacc acaggtgtac 1080 accctgcccc catcccggga tgagctgacc aagaaccagg tcagcctgac ctgcctggtc 1140 aaaggcttct atcccagcga catcgccgtg gagtggggaga gcaatggggca gccggagaac 1200 aactacaaga ccacgcctcc cgtgctggac tccgacggct ccttcttcct ctacagcaag 1260 ctcaccgtgg acaagagcag gtggcagcag gggaacgtct tctcatgctc cgtgatgcat 1320 gaggctctgc acaaccacta cacgcagaag tccctctccc tgtctccggg taaatga 1377

<210> 620 <211> 458 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 620

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Asp Asp Tyr 25 30

Ala Met His Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Gly Ile Ser Trp Asn Arg Gly

55

Ser Ile Gly Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ala Lys Asn Ser Leu Tyr

80

- 512 044746

Leu

Ala

Asn

Ala

Ser 145

Phe

Gly

Leu

Tyr

Lys 225

Pro

Lys

Val

Tyr

Glu 305

His

Gln Met Ser

Lys Asp Gly

100

Gly Met Asp

115

Ser Thr Lys 130

Thr Ser Gly

Pro Glu Pro

Val His Thr

180

Ser Ser Val

195

Ile Cys Asn 210

Val Glu Pro

Ala Pro Glu

Pro Lys Asp

260

Val Val Asp

275

Val Asp Gly 290

Gln Tyr Asn

Gln Asp Trp

Ser Leu Arg 85

Glu Arg Trp

Val Trp Gly

Gly Pro Ser

135

Gly Thr Ala

150

Val Thr Val 165

Phe Pro Ala

Val Thr Val

Val Asn His

215

Lys Ser Cys

230

Leu Leu Gly 245

Thr Leu Met

Val Ser His

Val Glu Val

295

Ser Thr Tyr

310

Leu Asn Gly

Ala Glu Asp

Asp Ser Val

105

Gln Gly Thr 120

Val Phe Pro

Ala Leu Gly

Ser Trp Asn

170

Val Leu Gln

185

Pro Ser Ser 200

Lys Pro Ser

Asp Lys Thr

Gly Pro Ser 250

Ile Ser Arg 265

Glu Asp Pro 280

His Asn Ala

Arg Val Val

Lys Glu Tyr

Thr Ala Leu

Val Val Pro

Thr Val Thr

125

Leu Ala Pro

140

Cys Leu Val 155

Ser Gly Ala

Ser Ser Gly

Ser Leu Gly

205

Asn Thr Lys

220

His Thr Cys 235

Val Phe Leu

Thr Pro Glu

Glu Val Lys

285

Lys Thr Lys

300

Ser Val Leu 315

Lys Cys Lys

Tyr Tyr Cys 95

Ser Ala Arg 110

Val Ser Ser

Ser Ser Lys

Lys Asp Tyr

160

Leu Thr Ser

175

Leu Tyr Ser 190

Thr Gln Thr

Val Asp Lys

Pro Pro Cys

240

Phe Pro Pro

255

Val Thr Cys 270

Phe Asn Trp

Pro Arg Glu

Thr Val Leu

320

Val Ser Asn

- 513 044746

335

325

330

Lys Ala Leu Pro Ala Pro Ile Glu 340

Lys Thr Ile Ser Lys Ala Lys Gly

345 350

Gln Pro Arg Glu Pro Gln Val Tyr

355 360

Thr Leu Pro Pro Ser Arg Asp Glu 365

Leu Thr Lys Asn Gln Val Ser Leu

370 375

Thr Cys Leu Val Lys Gly Phe Tyr 380

Pro Ser Asp Ile Ala Val Glu Trp

385 390

Glu Ser Asn Gly Gln Pro Glu Asn

395 400

Asn Tyr Lys Thr Thr Pro Pro Val 405

Leu Asp Ser Asp Gly Ser Phe Phe

410 415

Leu Tyr Ser Lys Leu Thr Val Asp 420

Lys Ser Arg Trp Gln Gln Gly Asn

425 430

Val Phe Ser Cys Ser Val Met His

435 440

Glu Ala Leu His Asn His Tyr Thr 445

Gln Lys Ser Leu Ser Leu Ser Pro

450 455

Gly Lys

621

657

DNA

Artificial

Synthetic

621 <210>

<211>

<212> <213>

<220> <223>

<400>

cagtctgtgc tcctgcactg cttccaggaa cctgaccgat caggctgagg tatgtcttcg gtgaccctgt ctgatctccg gtgaaggccg tcctcctacc sequence tgacgcagcc ggagcagctc cagcccccaa tctctggctc atgaggctga gaactgggac tccccccctc acttctaccc gcgt ggagac tgtccctgac gccctcagtg caacatcggg actcctcatc caagtctggc ttattactgc caaggtcacc ctccgaggag cggcgccgtg caccaccccc ccccgagcag tctggggccc gcaggttatg tatggtaaca acctcagcct cagtcctatg gtcctaggcc ctgcaggcca accgtggcc t tccaagcagt tggaagtccc cagggcagag atgtacattg gcaatcggcc ccctggccat acagcagcct agcccaaggc acaaggccac ggaaggccga ccaacaacaa accggtccta ggtcaccatc gtaccagcag ctcaggggtc cactgggctc gagtggctct cgccccctcc cctggtgtgc ctcctccccc gtacgccgcc ctcctgccag

120

180

240

300

360

420

480

540

600

- 514 044746 gtgacccacg agggctccac cgtggagaag accgtggccc ccaccgagtg ctcctga

657 <210> 622 <211> 218 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 622

Gln Ser 1

Val Leu

Thr Gln 5

Pro Pro

Ser Val

Ser Gly

Ala Pro

Arg Val

Thr Ile

Ser Cys

Thr Gly

Ser Ser 25

Ser Asn

Ile Gly 30

Tyr Asp

Val His 35

Trp Tyr

Gln Gln

Leu Pro

Gly Thr

Ala Pro 45

Leu Ile

Tyr Gly

Asn Ser

Asn Arg 55

Pro Ser

Gly Val 60

Pro Asp

Gly Gln 15

Ala Gly

Lys Leu

Arg Phe

Ser Gly 65

Ser Lys

Ser Gly 70

Thr Ser

Ala Ser

Leu Ala 75

Ile Thr

Gly Leu 80

Gln Ala

Glu Asp

Glu Ala 85

Asp Tyr

Tyr Cys 90

Gln Ser

Tyr Asp

Ser Ser 95

Leu Ser

Gly Ser

100

Tyr Val

Phe Gly

Thr Gly 105

Thr Lys

Val Thr

110

Val Leu

Gly Gln

Pro Lys 115

Ala Ala

Pro Ser

120

Val Thr

Leu Phe

Pro Pro 125

Ser Ser

Glu Glu

130

Leu Gln

Ala Asn

Lys Ala 135

Thr Leu

Val Cys

140

Leu Ile

Ser Asp

Phe Tyr 145

Val Lys

Lys Tyr

Ser His

Pro Gly

Ala Gly

Ala Ala

180

Arg Ser

Ala Val

150

Val Glu 165

Ser Ser

Tyr Ser

Thr Val

Thr Thr

Tyr Leu

Cys Gln

Ala Trp

Lys Ala 155

Thr Pro

170

Ser Lys

Ser Leu 185

Thr Pro

Val Thr

His Glu

Asp Ser

Gln Ser

Glu Gln

190

Gly Ser

Ser Pro

160

Asn Asn

175

Trp Lys

Thr Val

- 515 044746

195 200205

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser

210215 <210>623 <211>357 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 623 gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca tacggtgact tggtggagtc cctctgaatt ggctagagtg agggcagatt gtctgagagc tgcattttga tgggggaggc caccgtcagt ggtctcagtt caccatctcc cgaggacacg ctactggggc ttggtccagc agcaactaca atttatagcg agagacaatt gctgtatatt cagggaaccc ctggggggtc tgagctgggt gtggtagcac ccaagaacac actgtgcgag tggtcaccgt cctgagactc ccgccaggct attttacgca gttgtatctt agctcttccc ctcc tca

120

180

240

300

357 <210> 624 <211> 119 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 624

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Glu Phe Thr Val Ser Ser Asn

thirty

Tyr Met Ser Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Ser Gly Gly Ser

55

Thr Phe Tyr Ala Asp Ser Val Lys 60

Gly Arg Phe Thr Ile Ser Arg Asp 65 70

Asn Ser Lys Asn Thr Leu Tyr Leu

80

Gln Met Asn Ser Leu Arg Ala Glu 85

Asp Thr Ala Val Tyr Tyr Cys Ala

95

- 516 044746

Arg Ala Leu Pro Tyr Gly Asp Leu His Phe Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser

115 <210> 625 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 625 gaattcaccg tcagtagcaa ctac <210> 626 <211> 8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 626

Glu Phe Thr Val Ser Ser Asn Tyr

5 <210> 627 <211> 39 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 627 gcgagagctc ttccctacgg tgacttgcat tttgactac <210> 628 <211> 13 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 628

Ala Arg Ala Leu Pro Tyr Gly Asp Leu His Phe Asp Tyr

5 10 <210>

<211>

<212>

629

336 DNA

- 517 044746 <213> Artificial sequence <220>

<223> Synthetic <400> 629

cagtctgtgc tgacgcagcc gccctcagtg tctggggccc cagggcagag ggtcaccatc 60 tcctgcactg ggagcagctc caacatcgggg acaggttatg atgtacactg gtaccagcag 120 cttccaggaa cagcccccaa actcctcatc tatggtaaca ccaatcggcc ctcaggggtc 180 cctgaccgat tctctggctc caagtctggc acctcagcct ccctggccat cactgggctc 240 caggctgagg atgaggctga ttattactgc cagtcctatg acagcagcct gagtgactct 300 tatgtcttcg gaactggac caaggtcacc gtccta 336

<210> 630 <211> 112 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>630

Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly Gln

5 10 15

Arg Val Thr Ile Ser Cys Thr Gly 20

Ser Ser Ser Asn Ile Gly Thr Gly 25 30

Tyr Asp Val His Trp Tyr Gln Gln

40

Leu Pro Gly Thr Ala Pro Lys Leu 45

Leu Ile Tyr Gly Asn Thr Asn Arg

55

Pro Ser Gly Val Pro Asp Arg Phe 60

Ser Gly Ser Lys Ser Gly Thr Ser 65 70

Ala Ser Leu Ala Ile Thr Gly Leu

80

Gln Ala Glu Asp Glu Ala Asp Tyr 85

Tyr Cys Gln Ser Tyr Asp Ser Ser

95

Leu Ser Asp Ser Tyr Val Phe Gly

100

Thr Gly Thr Lys Val Thr Val Leu

105 110 <210> 631 <211> 9 <212> DNA <213> Artificial sequence <220>

- 518 044746 <223> Synthetic <400>631 ggtaacacc <210>632 <211>3 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>632

Gly Asn Thr < 210>633 < 211>36 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>633 cagtcctatg acagcagcct gagtgactct tatgtc <210>634 <211>12 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>634

Gln Ser Tyr Asp Ser Ser Leu Ser Asp Ser Tyr Val

510 <210>635 <211>1350 <212> DNA <213> Artificial sequence

Synthetic

635 <220>

<223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg gactccgtga tggtggagtc cctctgaatt ggctagagtg agggcagatt tgggggaggc caccgtcagt ggtctcagtt caccatctcc ttggtccagc agcaactaca atttatagcg agagacaatt ctggggggtc tgagctgggt gtggtagca c ccaagaacac cctgagactc ccgccaggct attttacgca gttgtatctt

120

180

240

- 519 044746

caaatgaaca gtctgagagc cgaggacacg gctgtatatt actgtgcgag agctcttccc 300 tacggtgact tgcattttga ctactggggc cagggaaccc tggtcaccgt ctcctcagcc 360 tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctggggggc 420 acaggccc tggggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac ccagacctac 600 atctgcaacg tgaatcacaa gccagcaac accaaggtgg acaagaaagt tgagcccaaa 660 tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720 tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780 gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840 gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900 acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaagggag 960 tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020 gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080 accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140 gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgcc tcccgtgctg 1200 gactccgacg gctccttctt ccctacagc aagctcaccg tggacaagag caggtggcag 1260 caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacgcag 1320 aagtccctct ccctgtctcc gggtaaatga 1350

<210> 636 <211> 449 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 636

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Glu Phe Thr 25

Val Ser Ser Asn

Tyr Met Ser Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Ser Val Ile Tyr 50

Ser Gly Gly Ser 55

Thr Phe Tyr Ala 60

Asp Ser Val Lys

- 520 044746

Gly 65

Gln

Arg

Thr

Pro

Gly 145

Asn

Gln

Ser

Ser

Thr 225

Ser

Arg

Pro

Ala

Val

Arg Phe Thr Ile Ser 70

Met Asn Ser Leu Arg 85

Ala Leu Pro Tyr Gly 100

Leu Val Thr Val Ser

115

Leu Ala Pro Ser Ser 130

Cys Leu Val Lys Asp

150

Ser Gly Ala Leu Thr

165

Ser Ser Gly Leu Tyr 180

Ser Leu Gly Thr Gln

195

Asn Thr Lys Val Asp 210

His Thr Cys Pro Pro

230

Val Phe Leu Phe Pro

245

Thr Pro Glu Val Thr

260

Glu Val Lys Phe Asn

275

Lys Thr Lys Pro Arg 290

Ser Val Leu Thr Val

Arg Asp Asn Ser Lys 75

Ala Glu Asp Thr Ala 90

Asp Leu His Phe Asp 105

Ser Ala Ser Thr Lys

120

Lys Ser Thr Ser Gly 135

Tyr Phe Pro Glu Pro

155

Ser Gly Val His Thr

170

Ser Leu Ser Ser Val

185

Thr Tyr Ile Cys Asn

200

Lys Lys Val Glu Pro 215

Cys Pro Ala Pro Glu

235

Pro Lys Pro Lys Asp

250

Cys Val Val Val Asp

265

Trp Tyr Val Asp Gly

280

Glu Glu Gln Tyr Asn 295

Leu His Gln Asp Trp

Asn Thr Leu Tyr Leu 80

Val Tyr Tyr Cys Ala

Tyr Trp Gly Gln Gly 110

Gly Pro Ser Val Phe

125

Gly Thr Ala Ala Leu 140

Val Thr Val Ser Trp

160

Phe Pro Ala Val Leu

175

Val Thr Val Pro Ser

190

Val Asn His Lys Pro

205

Lys Ser Cys Asp Lys 220

Leu Leu Gly Gly Pro

240

Thr Leu Met Ile Ser

255

Val Ser His Glu Asp

270

Val Glu Val His Asn

285

Ser Thr Tyr Arg Val 300

Leu Asn Gly Lys Glu

- 521 044746

305

310

315

320

Tyr Lys

Cys Lys

Thr Ile

Ser Lys

340

Leu Pro

Pro Ser 355

Cys Leu

370

Val Lys

Ser Asn

385

Gly Gln

Asp Ser

Asp Gly

Ser Arg

Trp Gln

420

Ala Leu

His Asn 435

Val Ser 325

Ala Lys

Arg Asp

Gly Phe

Pro Glu 390

Ser Phe 405

Gln Gly

His Tyr

Asn Lys

Ala Leu

330

Pro Ala

Pro Ile

Lys

637

657

DNA

Artificial

Synthetic

637 <210>

<211>

<212> <213>

<220> <223>

<400>

cagtctgtgc tcctgcactg cttccaggaa cctgaccgat caggctgagg tatgtcttcg gtgaccctgt ctgatctccg

Gly Gln

Glu Leu

360

Tyr Pro 375

Asn Asn

Phe Leu

Asn Val

Thr Gln

440

Pro Arg 345

Glu Pro

Gln Val

350

Thr Lys

Ser Asp

Tyr Lys

Tyr Ser

410

Phe Ser 425

Lys Ser sequence tgacgcagcc ggagcagctc cagcccccaa tctctggctc atgaggctga gaactgggac tccccccctc acttctaccc gccctcagtg caacatcggg actcctcatc caagtctggc ttattactgc caaggtcacc ctccgaggag cggcgccgtg

Asn Gln

Val Ser 365

Ile Ala

380

Thr Thr 395

Lys Leu

Cys Ser

Leu Ser tctggggccc acaggttatg tatggtaaca acctcagcct cagtcctatg gtcctaggcc ctgcaggcca accgtggcct

Val Glu

Pro Pro

Thr Val

Val Met

430

Leu Se 445 cagggcagag atgtacactg ccaatcggcc ccctggccat acagcagcct agcccaaggc acaaggccac ggaaggccga

Glu Lys 335

Tyr Thr

Leu Thr

Trp Glu

Val Leu

400

Asp Lys 415

His Glu

Pro Gly ggtcaccatc gtaccagcag ctcaggggtc cactgggctc gagtgactct cgccccctcc cctggtgtgc ctcctccccc

120

180

240

300

360

420

480

- 522 044746 gtgaaggccg tcctcctacc gtgacccacg gcgtggagac tgtccctgac agggctccac caccaccccc ccccgagcag cgtggagaag tccaagcagt tggaagtccc accgtggccc ccaacaacaa accggtccta ccaccgagtg gtacgccgcc ctcctg ccag ctcctga

540

600

657 <210> 638 <211> 218 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 638

Gln Ser 1

Val Leu

Thr Gln 5

Pro Pro

Ser Val

Ser Gly

Ala Pro

Arg Val

Thr Ile

Ser Cys

Thr Gly

Ser Ser 25

Ser Asn

Ile Gly 30

Tyr Asp

Val His 35

Trp Tyr

Gln Gln

Leu Pro

Gly Thr

Ala Pro 45

Leu Ile

Tyr Gly

Asn Thr

Asn Arg 55

Pro Ser

Gly Val 60

Pro Asp

Gly Gln 15

Thr Gly

Lys Leu

Arg Phe

Ser Gly 65

Ser Lys

Ser Gly 70

Thr Ser

Ala Ser

Leu Ala 75

Ile Thr

Gly Leu 80

Gln Ala

Glu Asp

Glu Ala 85

Asp Tyr

Tyr Cys 90

Gln Ser

Tyr Asp

Ser Ser 95

Leu Ser

Asp Ser

100

Tyr Val

Phe Gly

Thr Gly 105

Thr Lys

Val Thr

110

Val Leu

Gly Gln

Pro Lys 115

Ala Ala

Pro Ser

120

Val Thr

Leu Phe

Pro Pro 125

Ser Ser

Glu Glu

130

Leu Gln

Ala Asn

Lys Ala 135

Phe Tyr 145

Pro Gly

Ala Val

150

Thr Val

Val Lys

Ala Gly

Val Glu 165

Thr Thr

Lys Tyr

Ala Ala

Ser Ser

Tyr Leu

Thr Leu

Ala Trp

Thr Pro

170

Ser Leu

Val Cys

140

Leu Ile

Ser Asp

Lys Ala 155

Ser Lys

Thr Pro

Asp Ser

Gln Ser

Glu Gln

Ser Pro

160

Asn Asn

175

Trp Lys

- 523 044746

180 185190

Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly Ser Thr Val

195 200205

Glu Lys Thr Val Ala Pro Thr Glu Cys Ser

210215 <210>

<211>

<212>

<213>

639

360

DNA

Artificial sequence

Synthetic

639 <220>

<223>

<400>

caggtgcagc tcctgtgcag ccaggcaagg gcagactccg ctgcaaatga gactacggtg tggtggagtc cctctggatt ggctggagtg tgaagggccg acagcctgag actacttatt tgggggaggc caccttcagt ggtggcagtt attcaccatc aactgaggac ggtttactgg gtggtccagc a actatgcta atatcatatg tccagagaca acggctgtgt ggccagggaa ctgggaggtc tgtactgggt atggaagtaa attccaagaa attactgtgc ccctggtcac cctgagactc ccgccaggct taaatactat cacgctgtat gagtggctcc cgtctcctca

120

180

240

300

360 <210> 640 <211> 120 <212> PROTEIN <213> Artificial sequence <220>

< 223 > Synthetic < 400 > 640

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala

Ser Gly Phe Thr Phe Ser Asn Tyr 25 30

Ala Met Tyr Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ala Val Ile Ser Tyr Asp Gly Ser

55

Asn Lys Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ser Lys Asn Thr Leu Tyr

80

- 524 044746

Leu Gln Met Asn

Ser Leu Arg Thr Glu Asp Thr

90

Ala Val Tyr Tyr Cys 95

Ala Ser Gly Ser Asp Tyr Gly Asp Tyr Leu Leu Val

100 105

Tyr Trp Gly Gln

110

Gly Thr Leu Val Thr Val Ser Ser

115 120 <210> 641 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>641 ggattcacct tcagtaacta tgct <210>642 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 642

Gly Phe Thr Phe Ser Asn Tyr Ala

5 <210> 643 <211> 39 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>643 gcgagtggct ccgactacgg tgactactta ttggtttac <210>644 <211>13 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 644

Ala Ser Gly Ser Asp Tyr Gly Asp Tyr Leu Leu Val Tyr 1 5 10

- 525 044746 <210> 645 <211> 330 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 645

cagtctgccc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60 tcctgcactg gaaccagcag tgacgttggt ggttataact atgtctcctg gtaccaacaa 120 cacccaggca aagcccccaa actcatgatt tatgatgtca gtaagcggcc ctcaggggtt 180 tctaatcgct tctctggctc caagtctggc aacacggcct ccctgaccat ctctggggctc 240 cagtctgagg acgaggctga ttattactgc aactctttga caagcatcag cacttgggtg 300 ttcggcggag ggaccaagct gaccgtccta 330

<210> 646 <211> 110 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 646

Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln

5 10 15

Ser Ile Thr Ile Ser Cys Thr Gly 20

Thr Ser Ser Asp Val Gly Gly Tyr 25 30

Asn Tyr Val Ser Trp Tyr Gln Gln

40

His Pro Gly Lys Ala Pro Lys Leu 45

Met Ile Tyr Asp Val Ser Lys Arg

55

Pro Ser Gly Val Ser Asn Arg Phe 60

Ser Gly Ser Lys Ser Gly Asn Thr 65 70

Ala Ser Leu Thr Ile Ser Gly Leu

80

Gln Ser Glu Asp Glu Ala Asp Tyr 85

Tyr Cys Asn Ser Leu Thr Ser Ile

95

Ser Thr Trp Val Phe Gly Gly Gly

100

Thr Lys Leu Thr Val Leu

105 110 <210> 647 <211> 27

- 526 044746 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>647 agcagtgacg ttggtggtta taactat <210>648 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>648

Ser Ser Asp Val Gly Gly Tyr Asn Tyr < 210>649 < 211>9 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>649 gatgtcagt <210>650 <211>3 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>650

Asp Val Ser <210>651 <211>30 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 651 aactctttga caagcatcag cacttgggtg <210> 652

- 527 044746 <211> 10 < 212> PROTEIN < 213> Artificial sequence <220>

<223> Synthetic <400>652

Asn Ser Leu Thr Ser Ile Ser Thr Trp Val

510 <210>653 <211>1353 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 653 caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagt aactatgcta tgtactgggt ccgccaggct 120 ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactat 180 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag aactgaggac acggctgtgt attackgtgc gagtggctcc 300 gactacggtg actacttatt ggtttactgg ggccagggaa ccctggtcac cgtctcctca 360 gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacacc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcggggaga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtacacc tgcccccatc ccgggatgag 1080 ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140 gccgtggagt ggggagagcaa tggggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1260

- 528 044746 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg

1320

1353 cagaagtccc tctccctgtc tccgggtaaa tga <210> 654 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 654

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Ser Asn Tyr 25 30

Ala Met Tyr Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ala Val Ile Ser Tyr Asp Gly Ser

55

Asn Lys Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ser Lys Asn Thr Leu Tyr

80

Leu Gln Met Asn Ser Leu Arg Thr 85

Glu Asp Thr Ala Val Tyr Tyr Cys

95

Ala Ser Gly Ser Asp Tyr Gly Asp

100

Tyr Leu Leu Val Tyr Trp Gly Gln

105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

Ala Ser Thr Lys Gly Pro Ser Val

125

Phe Pro Leu Ala Pro Ser Ser Lys

130 135

Ser Thr Ser Gly Gly Thr Ala Ala

140

Leu Gly Cys Leu Val Lys Asp Tyr

145 150

Phe Pro Glu Pro Val Thr Val Ser

155 160

Trp Asn Ser Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe Pro Ala Val

170 175

Leu Gln Ser Ser Gly Leu Tyr Ser 180

Leu Ser Ser Val Val Thr Val Pro

185 190

- 529 044746

Ser

Pro

Lys 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Lys

Glu

Ser Ser Leu

195

Ser Asn Thr 210

Thr His Thr

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Leu Val 370

Ser Asn Gly

Asp Ser Asp

Ser Arg Trp

420

Ala Leu His

435

Gly Thr Gln

Lys Val Asp

215

Cys Pro Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Asp

Lys Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe 405

Gln Gln Gly

Asn His Tyr

Thr Tyr Ile 200

Lys Lys Val

Cys Pro Ala

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Gln

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Leu Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

410

Asn Val Phe

425

Thr Gln Lys 440

Cys Asn Val

205

Glu Pro Lys

220

Pro Glu Leu 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Ser Cys Ser

Ser Leu Ser

445

Asn His Lys

Ser Cys Asp

Leu Gly Gly

240

Leu Met Ile

255

Ser His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

415

Val Met His 430

Leu Ser Pro

- 530 044746

Gly Lys

450 <210> 655 <211> 651 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 655

cagtctgccc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60 tcctgcactg gaaccagcag tgacgttggt ggttataact atgtctcctg gtaccaacaa 120 cacccaggca aagcccccaa actcatgatt tatgatgtca gtaagcggcc ctcaggggtt 180 tctaatcgct tctctggctc caagtctggc aacacggcct ccctgaccat ctctggggctc 240 cagtctgagg acgaggctga ttattactgc aactctttga caagcatcag cacttgggtg 300 ttcggcggag ggaccaagct gaccgtccta ggccagccca aggccgcccc ctccgtgacc 360 ctgttccccc cctcctccga ggagctgcag gccaacaagg ccaccctggt gtgcctgatc 420 tccgacttct accccggcgc cgtgaccgtg gcctggaagg ccgactcctc ccccgtgaag 480 gccggcgtgg agaccaccac cccctccaag cagtccaaca acaagtacgc cgcctcctcc 540 tacctgtccc tgacccccga gcagtggaag tcccaccggt cctactcctg ccaggtgacc 600 cacgaggct ccaccgtgga gaagaccgtg gccccaccg agtgctcctg a 651

<210> 656 <211> 216 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 656

Gln Ser Ala Leu 1

Thr Gln Pro Ala 5

Ser Val Ser Gly 10

Ser Pro Gly Gln 15

Ser Ile Thr Ile

Ser Cys Thr Gly

Thr Ser Ser Asp 25

Val Gly Gly Tyr 30

Asn Tyr Val Ser

Trp Tyr Gln Gln 40

His Pro Gly Lys

Ala Pro Lys Leu 45

Met Ile Tyr Asp 50

Val Ser Lys Arg

Pro Ser Gly Val 60

Ser Asn Arg Phe

- 531 044746

Ser Gly 65

Gln Ser

Ser Thr

Pro Lys

Ser Lys

Glu Asp

Trp Val

100

Ala Ala 115

Leu Gln

130

Ala Asn

Ser Gly 70

Glu Ala 85

Phe Gly

Pro Ser

Lys Ala

Asn Thr

Asp Tyr

Gly Gly

Val Thr

120

Thr Leu 135

Ala Ser

Tyr Cys 90

Thr Lys 105

Leu Phe

Val Cys

Pro Gly 145

Ala Val

Thr Val

150

Ala Trp

Lys Ala

Ala Gly

Val Glu

Thr Thr 165

Thr Pro

Ser Lys

170

Ala Ala

Ser Ser

180

Tyr Leu

Ser Leu

Thr Pro 185

Arg Ser

Tyr Ser 195

Cys Gln

Val Thr

200

His Glu

Leu Thr 75

Asn Ser

Leu Thr

Pro Pro

Leu Ile

140

Asp Ser 155

Gln Ser

Glu Gln

Gly Ser

Ile Ser

Leu Thr

Val Leu

110

Ser Ser 125

Ser Asp

Ser Pro

Asn Asn

Trp Lys

190

Thr Val

205

Thr Val Ala Pro Thr Glu Cys Ser

210 215

657

381

DNA

Artificial

Synthetic

657 <210>

<211>

<212> <213>

<220> <223>

<400>

g agagccgag aatccaccac a

ttggtacagc aattatgaaa attagtagta atctccagag gacacggctg tactactaca ctggagggtc tgaactgggt ggagtggtag acaacgccaa tttattactg tggacgtctg

Gly Leu 80

Ser Ile 95

Gly Gln

Glu Glu

Phe Tyr

Val Lys

160

Lys Tyr 175

Ser His

Glu Lys cctgagactc ccgccaggct taccctacac gaactcactg tgcgagaagg gggcaaaggg

120

180

240

300

360

381

- 532 044746 <210> 658 <211> 127 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>658

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Phe Ser Asn Tyr 20 2530

Glu Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Tyr Ile Ser Ser Arg Ser Gly Ser Thr Leu His Tyr Ala Asp Ser 50 5560

Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu 65 70 7580

Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr 85 9095

Cys Ala Arg Arg Gly Asp Gly Thr Ser Ser Leu Ile His His Tyr Tyr

100 105110

Tyr Met Asp Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser

115 120125 <210>659 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>659 ggattcacct tcagtaatta tgaa <210>660 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic

- 533 044746 <400>660

Gly Phe Thr Phe Ser Asn Tyr Glu 15 <210>661 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>661 attagtagta ggagtggtag tacccta <210>662 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>662

Ile Ser Ser Arg Ser Gly Ser Thr Leu <210>663 <211>57 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>663 gcgagaaggg gcgatggtac cagctcccta atccaccact actactacat ggacgtc <210>664 <211>19 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 664

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

5 10 15

Met Asp Val

- 534 044746 <210> 665 <211> 330 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 665

cagtctgtgc tgactcagcc accctcagcg tctggggacc ccggggcagag ggtcaccatc 60 tcttgttctg gaagcagctc caacatcgga agtaatactg taaactggta ccaacagctc 120 caccagaacgg cccccaaact cctcatcatat agtaataatc agcggccctc aggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tggggctccag 240 tctgaggatg aggctgatta ttactgtgca gcatgggatg acagcctgaa tggtccggta 300 ttcggcggag ggaccaagct gaccgtccta 330

<210> 666 <211> 110 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>666

Gln Ser Val Leu Thr Gln Pro Pro Ser Ala Ser Gly Thr Pro Gly Gln

5 1015

Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn 20 2530

Thr Val Asn Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu 35 4045

Ile Tyr Ser Asn Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 5560

Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln 65 70 7580

Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Ala Ala Trp Asp Asp Ser Leu 85 9095

Asn Gly Pro Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu

100 105110 <210>667 <211>24 <212> DNA

- 535 044746 <213> Artificial sequence <220>

<223> Synthetic <400>667 agctccaaca tcggaagtaa tact <210>668 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>668

Ser Ser Asn Ile Gly Ser Asn Thr <210>669 <211>9 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>669 agtaataat <210>670 <211>3 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>670

Ser Asn Asn <210>671 <211>33 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 671 gcagcatggg atgacagcct gaatggtccg gta <210> 672 <211> 11

- 536 044746 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 672

Ala Ala Trp Asp Asp Ser Leu Asn Gly Pro Val

5 10 <210> 673 <211> 1374 <212> DNA <213> Artificial sequence

<220> <223> Synthetic <400> 673 gaggtgcagc tggtggagtc tgggggaggc ttggtacagc ctggagggtc cctgagactc 60 tcctgtacag cctctggatt caccttcagt aattatgaaa tgaactgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtttcatac attagtagta ggagtggtag taccctacac 180 tacgcagact ctgtgaaggg ccgattcacc atctccagag acaacgccaa gaactcactg 240 tatctgcaaa tgaacagcct gagagccgag gacacggctg tttattactg tgcgagaagg 300 ggcgatggta ccagctccct aatccaccac tactactaca tggacgtctg gggcaaaggg 360 accacggtca ccgtctcctc agcctccacc aagggcccat cggtcttccc cctggcaccc 420 tcctccaaga gcacctctgg gggcacagcg gccctgggct gcctggtcaa ggactacttc 480 cccgaaccgg tgacggtgtc gtggaactca ggcgccctga ccagcggcgt gcacaccttc 540 ccggctgtcc tacagtcctc aggactctac tccctcagca gcgtggtgac cgtgccctcc 600 agcagcttgg gcacccagac ctacatctgc aacgtgaatc acaagcccag caacaccaag 660 gtggacaaga aagttgagcc caaatcttgt gacaaaactc acacatgccc accgtgccca 720 gcacctgaac tcctgggggg accgtcagtc ttcctcttcc ccccaaaacc caaggacacc 780 ctcatgatct cccggacccc tgaggtcaca tgcgtggtgg tggacgtgag ccacgaagac 840 cctgaggtca agttcaactg gtacgtggac ggcgtggagg tgcataatgc caagacaaag 900 ccgcgggagg agcagtacaa cagcacgtac cgtgtggtca gcgtcctcac cgtcctgcac 960 caggactggc tgaatggcaa ggagtacaag tgcaaggtct ccaacaaagc cctcccagcc 1020 ccatcgaga aaaccatctc caaagccaaa gggcagcccc gagaaccaca ggtgtacacc 1080 ctgcccccat cccgggatga gctgaccaag aaccaggtca gcctgacctg cctggtcaaa 1140 ggcttctatc ccagcgacat cgccgtggag tggggagagca atggggcagcc ggagaacaac 1200 tacaagacca cgcctcccgt gctggactcc gacggctcct tcttcctcta cagcaagctc 1260

- 537 044746 accgtggaca agagcaggtg gcagcagggg gctctgcaca accactacac gcagaagtcc aacgtcttct catgctccgt gatgcatgag ctctccctgt ctccgggtaa atga

1320

1374 <210> 674 <211> 457 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 674

Glu Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly 10

Leu Val

Glin Pro

Ser Leu

Arg Leu 20

Ser Cys

Thr Ala

Ser Gly 25

Phe Thr

Phe Ser

GluMet

Asn Trp 35

Val Arg

Gln Ala

Pro Gly

Lys Gly

Leu Glu 45

Ser Tyr 50

Ile Ser

Ser Arg

Ser Gly 55

Ser Thr

Leu His

Tyr Ala

Gly Gly 15

Asn Tyr

Trp Val

Asp Ser

Val Lys 65

Gly Arg

Phe Thr

Ile Ser

Arg Asp

Asn Ala 75

Lys Asn

Ser Leu

Tyr Leu

Gln Met

Asn Ser 85

Leu Arg

Ala Glu

Asp Thr

Ala Val

Tyr Tyr 95

Cys Ala

Arg Arg

100

Gly Asp

Gly Thr

Ser Ser 105

Leu Ile

His His

110

Tyr Tyr

Tyr Met

Asp Val 115

Trp Gly

Lys Gly

120

Thr Thr

Val Thr

Val Ser 125

Ser Ala

Ser Thr

130

Lys Gly

Pro Ser

Val Phe 135

ProLeu

Ala Pro

140

Ser Ser

Lys Ser

Thr Ser 145

Gly Gly

Thr Ala

150

Ala Leu

Gly Cys

Leu Val 155

Lys Asp

Tyr Phe

160

Pro Glu

Pro Val

Thr Val 165

Ser Trp

Asn Ser

170

Gly Ala

Leu Thr

Ser Gly 175

Val His

Thr Phe

180

Pro Ala

Val Leu

Gln Ser 185

Ser Gly

Leu Tyr

190

Ser Leu

- 538 044746

Ser

Ile

Val 225

Ala

Pro

Val

Val

Gln 305

Gln

Ala

Pro

Thr

Ser 385

Tyr

Tyr

Phe

Ser Val Val

195

Cys Asn Val 210

Glu Pro Lys

Pro Glu Leu

Lys Asp Thr

260

Val Asp Val

275

Asp Gly Val 290

Tyr Asn Ser

Asp Trp Leu

Leu Pro Ala

340

Arg Glu Pro

355

Lys Asn Gln 370

Asp Ile Ala

Lys Thr Thr

Ser Lys Leu

420

Ser Cys Ser

435

Thr Val Pro

Ser Ser Ser 200

Leu Gly Thr

205

Gln Thr Tyr

Asn His Lys

215

Pro Ser Asn

Thr Lys Val

220

Asp Lys Lys

Ser Cys Asp

230

Leu Gly Gly 245

Leu Met Ile

Ser His Glu

Glu Val His

295

Thr Tyr Arg

310

Asn Gly Lys 325

Pro Ile Glu

Gln Val Tyr

Val Ser Leu

375

Val Glu Trp

390

Pro Pro Val 405

Thr Val Asp

Val Met His

Lys Thr His

Thr Cys Pro 235

Pro Cys Pro

240

Pro Ser Val

250

Phe Leu Phe

Pro Pro Lys

255

Ser Arg Thr

265

Pro Glu Val

Thr Cys Val 270

Asp Pro Glu 280

Val Lys Phe

285

Asn Trp Tyr

Asn Ala Lys

Val Val Ser

Glu Tyr Lys

330

Lys Thr Ile

345

Thr Leu Pro 360

Thr Cys Leu

Glu Ser Asn

Leu Asp Ser

410

Lys Ser Arg

425

Glu Ala Leu 440

Thr Lys Pro

300

Val Leu Thr 315

Cys Lys Val

Ser Lys Ala

Pro Ser Arg

365

Val Lys Gly

380

Gly Gln Pro 395

Asp Gly Ser

Trp Gln Gln

His Asn His

445

Arg Glu Glu

Val Leu His

320

Ser Asn Lys

335

Lys Gly Gln 350

Asp Glu Leu

Phe Tyr Pro

Glu Asn Asn

400

Phe Phe Leu

415

Gly Asn Val 430

Tyr Thr Gln

- 539 044746

Lys Ser Leu Ser Leu Ser Pro Gly Lys

450455 <210>675 <211>651 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 675

cagtctgtgc tgactcagcc accctcagcg tctggggacc ccggggcagag ggtcaccatc 60 tcttgttctg gaagcagctc caacatcgga agtaatactg taaactggta ccaacagctc 120 caccagaacgg cccccaaact cctcatcatat agtaataatc agcggccctc aggggtccct 180 gaccgattct ctggctccaa gtctggcacc tcagcctccc tggccatcag tggggctccag 240 tctgaggatg aggctgatta ttactgtgca gcatgggatg acagcctgaa tggtccggta 300 ttcggcggag ggaccaagct gaccgtccta ggccagccca aggccgcccc ctccgtgacc 360 ctgttccccc cctcctccga ggagctgcag gccaacaagg ccaccctggt gtgcctgatc 420 tccgacttct accccggcgc cgtgaccgtg gcctggaagg ccgactcctc ccccgtgaag 480 gccggcgtgg agaccaccac cccctccaag cagtccaaca acaagtacgc cgcctcctcc 540 tacctgtccc tgacccccga gcagtggaag tcccaccggt cctactcctg ccaggtgacc 600 cacgaggct ccaccgtgga gaagaccgtg gccccaccg agtgctcctg a 651

<210> 676 <211> 216 <212> PROTEIN <213> Artificial sequence <220>

< 223 > Synthetic < 400 > 676

Gln Ser Val Leu Thr Gln Pro Pro 1 5

Ser Ala Ser Gly Thr Pro Gly Gln

15

Arg Val Thr Ile Ser Cys Ser Gly 20

Ser Ser Ser Asn Ile Gly Ser Asn 25 30

Thr Val Asn Trp Tyr Gln Gln Leu

40

Pro Gly Thr Ala Pro Lys Leu Leu 45

Ile Tyr Ser Asn Asn Gln Arg Pro

55

Ser Gly Val Pro Asp Arg Phe Ser 60

- 540 044746

Gly Ser 65

Ser Glu

Asn Gly

Pro Lys

Lys Ser

Asp Glu

Pro Val

100

Ala Ala 115

Leu Gln

130

Ala Asn

Gly Thr 70

Ala Asp 85

Phe Gly

Pro Ser

Lys Ala

Ser Ala

Tyr Tyr

Gly Gly

Val Thr

120

Thr Leu 135

Ser Leu

Cys Ala

Thr Lys 105

Leu Phe

Val Cys

Pro Gly 145

Ala Val

Thr Val

150

Ala Trp

Lys Ala

Ala Gly

Val Glu

Thr Thr 165

Thr Pro

Ser Lys

170

Ala Ala

Ser Ser

180

Tyr Leu

Ser Leu

Thr Pro 185

Arg Ser

Tyr Ser 195

Cys Gln

Val Thr

200

His Glu

Ala Ile 75

Ala Trp

Leu Thr

Pro Pro

Leu Ile 140

Asp Ser 155

Gln Ser

Glu Gln

Gly Ser

Ser Gly

Asp Asp

Val Leu

110

Ser Ser 125

Ser Asp

Ser Pro

Asn Asn

Trp Lys

190

Thr Val

205

Leu Gln

Ser Leu 95

Gly Gln

Glu Glu

Phe Tyr

Val Lys

160

Lys Tyr 175

Ser His

Glu Lys

Thr Val Ala Pro Thr Glu Cys Ser

210 215 <210>

<211>

<212>

<213>

677

369

DNA

Artificial sequence <220>

<223> Synthetic <400> 677 caggtgcagc tcctgcaagg cctggacagg gcacagaagt atggaactga cggtatgact tggtgcagtc cttctggata ggcttgagtg ttcagggcag gcaggctgag ggaaccagaa tggggctgag catcttcacc gatgggatgg ggtcaccctg atttga cgac caactggttc gtgaagaagc ggctactata atcaacccta accagggaca acggccgtgt gacccctggg ctggggcctc tgcactgggt acagtggtgg cgtccatcac attactgtgc gccagggaac agtgaaggtc gcgacaggcc cgcaaactat cacagtctac gagaggatcc cctggtcacc gtctcc tca

120

180

240

300

360

369

- 541 044746 <210> 678 <211> 123 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 678

Gln Val Gln Leu Val Gln Ser Gly 1 5

Ala Glu Val Lys Lys Pro Gly Ala

15

Ser Val Lys Val Ser Cys Lys Ala 20

Ser Gly Tyr Ile Phe Thr Gly Tyr

thirty

Tyr Met His Trp Val Arg Gln Ala

40

Pro Gly Gln Gly Leu Glu Trp Met 45

Gly Trp Ile Asn Pro Asn Ser Gly

55

Gly Ala Asn Tyr Ala Gln Lys Phe 60

Gln Gly Arg Val Thr Leu Thr Arg 65 70

Asp Thr Ser Ile Thr Thr Val Tyr

80

Met Glu Leu Ser Arg Leu Arg Phe 85

Asp Asp Thr Ala Val Tyr Tyr Cys

95

Ala Arg Gly Ser Arg Tyr Asp Trp

100

Asn Gln Asn Asn Trp Phe Asp Pro

105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115120 <210>679 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>679 ggatacatct tcaccggcta ctat <210>680 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic

- 542 044746 <400> 680

Gly Tyr Ile Phe Thr Gly Tyr Tyr 1 5 <210> 681 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 681 atcaacccta acagtggtgg cgca <210> 682 <211> 8 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 682

Ile Asn Pro Asn Ser Gly Gly Ala

5 <210> 683 <211> 48 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 683 gcgagaggat cccggtatga ctggaaccag aacaactggt tcgacccc <210> 684 <211> 16 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 684

Ala Arg Gly Ser Arg Tyr Asp Trp Asn Gln Asn Asn Trp Phe Asp Pro

5 10 15 <210> 685 <211> 330 <212> DNA <213>

Artificial sequence

- 543 044746 <220>

<223> Synthetic <400>685 cagtctgccc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc60 tcctgcactg gaaccagcag tgacgttggt acttataact atgtctcctg gtaccaacaa120 cacccaggca aagcccccaa actcatgatt tttgatgt ca gtaatcggcc ctcaggggtt180 tctgatcgct tctctggctc caagtctggc aacacggcct ccctgaccat ctctgggctc240 caggctgagg acgaggctga ttattactgc agctcattta caaccagcag cactgtggtt300 ttcggcggag ggaccaagct gaccgtccta330 <210>68 6 <211>110 < 212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 686

Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln

5 10 15

Ser Ile Thr Ile Ser Cys Thr Gly 20

Thr Ser Ser Asp Val Gly Thr Tyr 25 30

Asn Tyr Val Ser Trp Tyr Gln Gln

40

His Pro Gly Lys Ala Pro Lys Leu 45

Met Ile Phe Asp Val Ser Asn Arg

55

Pro Ser Gly Val Ser Asp Arg Phe 60

Ser Gly Ser Lys Ser Gly Asn Thr 65 70

Ala Ser Leu Thr Ile Ser Gly Leu

80

Gln Ala Glu Asp Glu Ala Asp Tyr 85

Tyr Cys Ser Ser Phe Thr Thr Ser

95

Ser Thr Val Val Phe Gly Gly Gly

100

Thr Lys Leu Thr Val Leu

105 110 <210> 687 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

- 544 044746 <400>687 agcagtgacg ttggtactta taactat <210>688 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>688

Ser Ser Asp Val Gly Thr Tyr Asn Tyr < 210>689 < 211>30 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>689 agctcattta caaccagcag cactgtggtt <210>690 <211>10 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>690

Ser Ser Phe Thr Thr Ser Ser Thr Val Val

510 <210>691 <211>1362 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic < 400>691 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc60 tcctgcaagg cttctggata catcttcacc ggctactata tgcactgggt gcgacaggcc120 cctggacagg ggcttgagtg gatgggatgg at caacccta acagtggtgg cgcaaactat180 gcacagaagt ttcagggcag ggtcaccctg accagggaca cgtccatcac cacagtctac240 atggaactga gcaggctgag atttgacgac acggccgtgt attactgtgc gagaggatcc300

- 545 044746

cggtatgact ggaaccagaa caactggttc gacccctggg gccagggaac cctggtcacc 360 gtctcctcag cctccaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc 420 acctctgggg gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 480 acggtgtcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 540 cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttggggc 600 accaccacct acatctgcaa cgtgaatcac aagccagca acaccaaggt ggacaagaaa 660 gttgagccca aatcttgtga caaaactcac acatgcccac cgtgcccagc acctgaactc 720 ctggggggac cgtcagtctt cctcttcccc ccaaaaccca aggacaccct catgatctcc 780 cggacccctg aggtcacatg cgtggtggtg gacgtgagcc acgaagaaccc tgaggtcaag 840 ttcaactggt acgtggacgg cgtggaggtg cataatgcca agacaaagcc gcgggaggag 900 cagtacaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg 960 aatggcaagg agtacaagtg caaggtctcc aacaaagccc tccagcccc catcgagaaa 1020 accatctcca aagccaaagg gcagccccga gaaccacagg tgtacaccct gcccccatcc 1080 cgggatgagc tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctatccc 1140 agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg 1200 cctcccgtgc tggactccga cggctccttc ttcctctaca gcaagctcac cgtggacaag 1260 agcaggtggc agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac 1320 cactacacgc agaagtccct ctccctgtct ccggggtaaat ga 1362

<210> 692 <211> 453 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 692

Gln Val Gln Leu 1

Val Gln Ser Gly 5

Ala Glu Val Lys 10

Lys Pro Gly Ala

Ser Val Lys Val 20

Ser Cys Lys Ala

Ser Gly Tyr Ile 25

Phe Thr Gly Tyr 30

Tyr Met His Trp 35

Val Arg Gln Ala 40

Pro Gly Gln Gly

Leu Glu Trp Met 45

Gly Trp Ile Asn 50

Pro Asn Ser Gly 55

Gly Ala Asn Tyr 60

Ala Gln Lys Phe

- 546 044746

Gln 65

Met

Ala

Trp

Pro

Thr 145

Thr

Pro

Thr

Asn

Ser 225

Leu

Leu

Ser

Glu

Thr 305

Gly Arg

Glu Leu

Arg Gly

Gly Gln

115

Ser Val 130

Ala Ala

Val Ser

Ala Val

Val Pro

195

His Lys 210

Cys Asp

Gly Gly

Met Ile

His Glu

275

Val His 290

Tyr Arg

Val Thr

Ser Arg

Ser Arg 100

Gly Thr

Phe Pro

Leu Gly

Trp Asn

165

Leu Gln 180

Ser Ser

Pro Ser

Lys Thr

Pro Ser

245

Ser Arg 260

Asp Pro

Asn Ala

Val Val

Leu Thr 70

Leu Arg

Tyr Asp

Leu Val

Leu Ala

135

Cys Leu 150

Ser Gly

Ser Ser

Ser Leu

Asn Thr

215

His Thr 230

Val Phe

Thr Pro

Glu Val

Lys Thr

295

Ser Val

310

Arg Asp

Phe Asp

Trp Asn

105

Thr Val 120

Pro Ser

Val Lys

Ala Leu

Gly Leu

185

Gly Thr 200

Lys Val

Cys Pro

Leu Phe

Glu Val

265

Lys Phe 280

Lys Pro

Leu Thr

Thr Ser

Ile Thr

Thr Val

Asp Thr 90

Ala Val

Tyr Tyr

Gln Asn

Ser Ser

Ser Lys

Asp Tyr

155

Thr Ser 170

Tyr Ser

Gln Thr

Asp Lys

Pro Cys

235

Pro Pro 250

Thr Cys

Asn Trp

Arg Glu

Val Leu

315

Asn Trp

Ala Ser

125

Ser Thr 140

Phe Pro

Gly Val

Leu Ser

Tyr Ile

205

Lys Val 220

Pro Ala

Lys Pro

Val Val

Tyr Val

285

Glu Gln 300

His Gln

Phe Asp 110

Thr Lys

Ser Gly

Glu Pro

His Thr

175

Ser Val 190

Cys Asn

Glu Pro

Pro Glu

Lys Asp

255

Val Asp 270

Asp Gly

Tyr Asn

Asp Trp

Tyr 80

Cys

Pro

Gly

Gly

Val 160

Phe

Val

Val

Lys

Leu 240

Thr

Val

Val

Ser

Leu 320

- 547 044746

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

325 330335

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

340 345350

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

355 360365

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

370 375380

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

385 390 395400

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

405 410415

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

420 425430

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

435 440445

Leu Ser Pro Gly Lys

450

<210> <211> <212> <213> 693 651 DNA Artificial sequence <220> <223> Synthetic <400> 693 cagtctgccc tgactcagcc tgcctccgtg tctgggtctc ctggacagtc gatcaccatc 60 tcctgcactg gaaccagcag tgacgttggt acttataact atgtctcctg gtaccaacaa 120 cacccaggca aagcccccaa actcatgatt tttgatgtca gtaatcggcc ctcaggggtt 180 tctgatcgct tctctggctc caagtctggc aacacggcct ccctgaccat ctctggggctc 240 caggctgagg acgaggctga ttattactgc agctcatta caaccagcag cactgtggtt 300 ttcggcggag ggaccaagct gaccgtccta ggccagccca aggccgcccc ctccgtgacc 360 ctgttccccc cctcctccga ggagctgcag gccaacaagg ccaccctggt gtgcctgatc 420 tccgacttct accccggcgc cgtgaccgtg gcctggaagg ccgactcctc ccccgtgaag 480 gccggcgtgg agaccaccac cccctccaag cagtccaaca acaagtacgc cgcctcctcc 540

- 548 044746 tacctgtccc tgacccccga cacgagggct ccaccgtgga gcagtggaag tcccaccggt gaagaccgtg gcccccaccg cctactcctg ccaggtgacc agtgctcctg a

600

651 <210> 694 <211> 216 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 694

Gln Ser 1

Ala Leu

Thr Gln 5

Pro Ala

Ser Val

Ser Gly

Ser Pro

Ser Ile

Thr Ile

Ser Cys

Thr Gly

Thr Ser 25

Ser Asp

Val Gly 30

Asn Tyr

Val Ser 35

Trp Tyr

Gln Gln

His Pro

Gly Lys

Ala Pro 45

Met Ile

Phe Asp

Val Ser

Asn Arg 55

Pro Ser

Gly Val 60

Ser Asp

Gly Gln 15

Thr Tyr

Lys Leu

Arg Phe

Ser Gly 65

Ser Lys

Ser Gly 70

Asn Thr

Ala Ser

Leu Thr 75

Ile Ser

Gly Leu 80

Gln Ala

Glu Asp

Glu Ala 85

Asp Tyr

Tyr Cys 90

Ser Ser

Phe Thr

Thr Ser 95

Ser Thr

Val Val

100

Phe Gly

Gly Gly

Thr Lys 105

Leu Thr

Val Leu

110

Gly Gln

Pro Lys

Ala Ala 115

Pro Ser

Val Thr

120

Leu Phe

Pro Pro

Ser Ser 125

Glu Glu

Leu Gln

130

Ala Asn

Lys Ala

Thr Leu 135

Val Cys

Leu Ile

140

Ser Asp

Phe Tyr

Pro Gly 145

Ala Val

Thr Val

150

Ala Trp

Lys Ala

Asp Ser 155

Ser Pro

Val Lys

160

Ala Gly

Val Glu

Thr Thr 165

Thr Pro

Ser Lys

170

Gln Ser

Asn Asn

Lys Tyr 175

Ala Ala

Ser Ser

180

Tyr Leu

Ser Leu

Thr Pro 185

Glu Gln

Trp Lys

190

Ser His

- 549 044746

Arg Ser Tyr Ser Cys Gln Val Thr His Glu Gly

Ser Thr Val Glu Lys

195 200 205

Thr Val Ala Pro Thr Glu Cys Ser

210 215 <210> 695 <211> 1338 <212> DNA <213> Artificial sequence

<220> <223> Synthetic <400> 695 gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggact caccgtcaat cgcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcactt atttatagcg gtggtagcac atactacgca 180 gactccgtta aggggccgatt caccattctcc agagacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagact tgaggacacg gctgtgtatt actgtgcgag aggtgaactg 300 ggggatcccct acggtatgga cgtctggggc caagggacca cggtcaccgt ctcctcagcc 360 tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc 420 acagccgccc tggggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac gaagacctac 600 acctgcaacg tagatcacaa gccagcaac accaaggtgg acaagagt tgagtccaaa 660 tatggtcccc catgcccacc gtgccagca ccaggcggtg gcggaccatc agtcttcctg 720 ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 780 gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 840 gaggtgcata atgccaagac aaagccgcgg gagggagt tcaacagcac gtaccgtgtg 900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaagggagta caagtgcaag 960 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1020 ccccgagagc cacaggtgta caccctgccc ccaccagg aggagatgac caagaaccag 1080 gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtggggag 1140 agcaatggggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200 tccttcttcc tctacagcag gctcaccgtg gacaagagca ggtggcagga ggggaatgtc 1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gtccctctcc 1320 ctgtctctgg gtaaatga 1338

- 550 044746 <210> 696 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 696

Glu Val Gln Leu Val

5

Glu Ser Gly Gly Gly

Leu Val Gln Pro Gly

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Leu Thr Val Asn Arg 30

Tyr Met Ser Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Ser Leu Ile Tyr Ser 50

Gly Gly Ser Thr Tyr 55

Tyr Ala Asp Ser Val 60

Gly Arg Phe Thr Ile 65

Ser Arg Asp Asn Ser 70

Lys Asn Thr Leu Tyr 75

Gln Met Asn Ser Leu

Arg Leu Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Gly Glu Leu Gly

100

Ile Pro Tyr Gly Met

105

Asp Val Trp Gly Gln

110

Thr Thr Val Thr Val

115

Ser Ser Ala Ser Thr

120

Lys Gly Pro Ser Val 125

Pro Leu Ala Pro Cys

130

Ser Arg Ser Thr Ser

135

Glu Ser Thr Ala Ala

140

Gly Cys Leu Val Lys 145

Asp Tyr Phe Pro Glu 150

Pro Val Thr Val Ser 155

Asn Ser Gly Ala Leu

165

Thr Ser Gly Val His

170

Thr Phe Pro Ala Val

175

Gln Ser Ser Gly Leu

180

Tyr Ser Leu Ser Ser

185

Val Val Thr Val Pro

190

Ser Ser Leu Gly Thr

195

Lys Thr Tyr Thr Cys 200

Asn Val Asp His Lys 205

Gly

Asn

Val

Lys

Leu 80

Ala

Gly

Phe

Leu

Trp 160

Leu

Ser

Pro

- 551 044746

Ser Asn Thr Lys Val

210

Asp Lys Arg Val Glu

215

Ser Lys Tyr Gly Pro

220

Cys Pro Pro Cys Pro 225

Ala Pro Gly Gly Gly 230

Gly Pro Ser Val Phe 235

Phe Pro Pro Lys Pro

245

Lys Asp Thr Leu Met

250

Ile Ser Arg Thr Pro

255

Val Thr Cys Val Val

260

Val Asp Val Ser Gln

265

Glu Asp Pro Glu Val

270

Phe Asn Trp Tyr Val

275

Asp Gly Val Glu Val 280

His Asn Ala Lys Thr

285

Pro Arg Glu Glu Gln 290

Phe Asn Ser Thr Tyr

295

Arg Val Val Ser Val

300

Thr Val Leu His Gln 305

Asp Trp Leu Asn Gly 310

Lys Glu Tyr Lys Cys 315

Val Ser Asn Lys Gly

325

Leu Pro Ser Ser Ile

330

Glu Lys Thr Ile Ser

335

Ala Lys Gly Gln Pro

340

Arg Glu Pro Gln Val

345

Tyr Thr Leu Pro Pro

350

Gln Glu Glu Met Thr

355

Lys Asn Gln Val Ser 360

Leu Thr Cys Leu Val

365

Gly Phe Tyr Pro Ser

370

Asp Ile Ala Val Glu

375

Trp Glu Ser Asn Gly

380

Pro Glu Asn Asn Tyr 385

Lys Thr Thr Pro Pro 390

Val Leu Asp Ser Asp 395

Ser Phe Phe Leu Tyr

405

Ser Arg Leu Thr Val

410

Asp Lys Ser Arg Trp

415

Glu Gly Asn Val Phe

420

Ser Cys Ser Val Met

425

His Glu Ala Leu His

430

Pro

Leu 240

Glu

Gln

Lys

Leu

Lys 320

Lys

Ser

Lys

Gln

Gly 400

Gln

Asn

His Tyr Thr Gln Lys

435

Ser Leu Ser Leu Ser

440

Leu Gly Lys

445 <210> 697 <211> 1365

- 552 044746 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>697 gaagtgcagc tggtggagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc60 tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct120 ccagggaagg gcctggagtg ggtctcaggt attag ttgga ataggggtag cataggctat180 gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat240 ctgcaaatga gcagtctgag agctgaggac acggccttgt attactgcgc aaaagatggc300 gagagatggg atagtgtagt agtaccatct gctaggaacg gtatggacgt ctggggccaa360 gggaccacgg tcaccgtctc ctcagcctcc accaagggcc catcggtctt ccccctggcg420 ccctgctcca ggagcacctc cgagagcaca gccgccctgg gctgcctggt caaggactac480 ttccccgaac cggtgacggt gtcgtggaac tcaggcgccc tgaccagcgg cgtgcacacc540 ttcccggctg tcctacagtc ctcaggactc tactccctca gcagcgtggt gaccgtg ccc600 tccagcagct tgggcacgaa gacctacacc tgcaacgtag atcacaagcc cagcaacacc660 aaggtggaca agagagttga gtccaaatat ggtcccccat gcccaccgtg cccagcacca720 ggcggtggcg gaccatcagt cttcctgttc cccccaaaac ccaaggacac tctcatgat c780 tcccggaccc ctgaggtcac gtgcgtggtg gtggacgtga gccaggaaga ccccgaggtc840 cagttcaact ggtacgtgga tggcgtggag gtgcataatg ccaagacaaa gccgcgggag900 gagcagttca acagcacgta ccgtgtggtc agcgtcctca ccgtcctgca ccaggactgg960 ctgaacggca aggagtacaa gtgcaaggtc tccaacaaag gcctcccgtc ctccatcgag1020 aaaaccatct ccaaagccaa agggcagccc cgagagccac aggtgtacac cctgccccca1080 tc cccaggagg agatgaccaa gaaccaggtc agcctgacct gcctggtcaa aggcttctac1140 cccagcgaca tcgccgtgga gtggggagagc aatgggcagc cggagaacaa ctacaagacc1200 acgcctcccg tgctggactc cgacggctcc ttcttcctct acagcaggct caccgtggac12 60 aagagcaggt ggcaggaggg gaatgtcttc tcatgctccg tgatgcatga ggctctgcac1320 aaccactaca cacagaagtc cctctccctg tctctgggta aatga1365 <210>698 < 211>454 <212> PROTEIN <213> Artificial sequence <220>

<223>

Synthetic <400>

698

- 553 044746

Glu 1

Ser

Ala

Ser

Lys 65

Leu

Ala

Asn

Ala

Ser 145

Phe

Gly

Leu

Tyr

Arg 225

Gly

Val Gln Leu Val Glu

Leu Arg Leu Ser Cys 20

Met His Trp Val Arg 35

Gly Ile Ser Trp Asn 50

Gly Arg Phe Thr Ile 70

Gln Met Ser Ser Leu

Lys Asp Gly Glu Arg 100

Gly Met Asp Val Trp 115

Ser Thr Lys Gly Pro 130

Thr Ser Glu Ser Thr

150

Pro Glu Pro Val Thr

165

Val His Thr Phe Pro

180

Ser Ser Val Val Thr

195

Thr Cys Asn Val Asp 210

Val Glu Ser Lys Tyr

230

Gly Gly Gly Pro Ser

245

Ser Gly Gly Gly Leu

Ala Ala Ser Gly Phe 25

Gln Ala Pro Gly Lys 40

Arg Gly Ser Ile Gly 55

Ser Arg Asp Asn Ala 75

Arg Ala Glu Asp Thr

Trp Asp Ser Val Val 105

Gly Gln Gly Thr Thr

120

Ser Val Phe Pro Leu 135

Ala Ala Leu Gly Cys

155

Val Ser Trp Asn Ser

170

Ala Val Leu Gln Ser

185

Val Pro Ser Ser Ser

200

His Lys Pro Ser Asn 215

Gly Pro Pro Cys Pro

235

Val Phe Leu Phe Pro

250

Val Gln Pro Gly Arg

Thr Phe Asp Asp Tyr 30

Gly Leu Glu Trp Val 45

Tyr Ala Asp Ser Val 60

Lys Asn Ser Leu Tyr 80

Ala Leu Tyr Tyr Cys 95

Val Pro Ser Ala Arg

110

Val Thr Val Ser Ser

125

Ala Pro Cys Ser Arg 140

Leu Val Lys Asp Tyr

160

Gly Ala Leu Thr Ser

175

Ser Gly Leu Tyr Ser 190

Leu Gly Thr Lys Thr

205

Thr Lys Val Asp Lys 220

Pro Cys Pro Ala Pro

240

Pro Lys Pro Lys Asp

255

- 554 044746

Thr Leu Met

Ile Ser Arg 260

Thr Pro Glu

265

Val Ser Gln

275

Glu Asp Pro

Glu Val Gln

280

Val Glu Val

290

His Asn Ala

Lys Thr Lys 295

Ser Thr Tyr 305

Arg Val Val

310

Ser Val Leu

Leu Asn Gly

Lys Glu Tyr

325

Lys Cys Lys

Ser Ser Ile

Glu Lys Thr 340

Ile Ser Lys

345

Pro Gln Val

355

Tyr Thr Leu

Pro Pro Ser

360

Gln Val Ser

370

Leu Thr Cys

Leu Val Lys 375

Ala Val Glu 385

Trp Glu Ser

390

Asn Gly Gln

Thr Pro Pro

Val Leu Asp

405

Ser Asp Gly

Leu Thr Val

Asp Lys Ser 420

Arg Trp Gln

425

Ser Val Met

435

His Glu Ala

Leu His Asn

440

Val Thr Cys

Phe Asn Trp

Pro Arg Glu 300

Thr Val Leu 315

Val Ser Asn 330

Ala Lys Gly

Gln Glu Glu

Gly Phe Tyr 380

Pro Glu Asn 395

Ser Phe Phe 410

Glu Gly Asn

His Tyr Thr

Val Val Val

270

Tyr Val Asp 285

Glu Gln Phe

His Gln Asp

Lys Gly Leu

335

Gln Pro Arg

350

Met Thr Lys 365

Pro Ser Asp

Asn Tyr Lys

Leu Tyr Ser

415

Val Phe Ser

430

Gln Lys Ser 445

Asp

Gly

Asn

Trp 320

Pro

Glu

Asn

Ile

Thr 400

Arg

Cys

Leu

Ser Leu Ser

450

Leu Gly Lys <210> 699 <211> 1338 <212> DNA <213> Artificial Sequence <220>

<223> Synthetic <400> 699

- 555 044746

gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctgaatt caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctagagtg ggtctcagtt atttatagcg gtggtagcac attttacgca 180 gactccgtga aggggatt caccattctcc agagacaatt ccaagaacac gttgtatctt 240 caaatgaaca gtctgagagc cgaggacacg gctgtatatt actgtgcgag agctcttccc 300 tacggtgact tgcattttga ctactggggc cagggaaccc tggtcaccgt ctcctcagcc 360 tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc 420 acagccgccc tggggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac gaagacctac 600 acctgcaacg tagatcacaa gccagcaac accaaggtgg acaagagt tgagtccaaa 660 tatggtcccc catgcccacc gtgccagca ccaggcggtg gcggaccatc agtcttcctg 720 ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 780 gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 840 gaggtgcata atgccaagac aaagccgcgg gagggagt tcaacagcac gtaccgtgtg 900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaagggagta caagtgcaag 960 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1020 ccccgagagc cacaggtgta caccctgccc ccaccagg aggagatgac caagaaccag 1080 gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtggggag 1140 agcaatggggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200 tccttcttcc tctacagcag gctcaccgtg gacaagagca ggtggcagga ggggaatgtc 1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gtccctctcc 1320 ctgtctctgg gtaaatga 1338

<210> 700 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>700

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser 2025

Glu Phe Thr Val Ser Ser Asn

- 556 044746

Tyr Met Ser 35 Trp Val Arg Gln Ala 40 Pro Gly Lys Gly Leu 45 Glu Trp Val Ser Val 50 Ile Tyr Ser Gly Gly 55 Ser Thr Phe Tyr Ala 60 Asp Ser Val Lys Gly 65 Arg Phe Thr Ile Ser 70 Arg Asp Asn Ser Lys 75 Asn Thr Leu Tyr Leu 80 Gln Met Asn Ser Leu 85 Arg Ala Glu Asp Thr 90 Ala Val Tyr Tyr Cys 95 Ala Arg Ala Leu Pro 100 Tyr Gly Asp Leu His 105 Phe Asp Tyr Trp Gly 110 Gln Gly Thr Leu Val 115 Thr Val Ser Ser Ala 120 Ser Thr Lys Gly Pro 125 Ser Val Phe Pro Leu 130 Ala Pro Cys Ser Arg 135 Ser Thr Ser Glu Ser 140 Thr Ala Ala Leu Gly 145 Cys Leu Val Lys Asp 150 Tyr Phe Pro Glu Pro 155 Val Thr Val Ser Trp 160 Asn Ser Gly Ala Leu 165 Thr Ser Gly Val His 170 Thr Phe Pro Ala Val 175 Leu Gln Ser Ser Gly 180 Leu Tyr Ser Leu Ser 185 Ser Val Val Thr Val 190 Pro Ser Ser Ser Leu 195 Gly Thr Lys Thr Tyr 200 Thr Cys Asn Val Asp 205 His Lys Pro Ser Asn 210 Thr Lys Val Asp Lys 215 Arg Val Glu Ser Lys 220 Tyr Gly Pro Pro Cys 225 Pro Pro Cys Pro Ala 230 Pro Gly Gly Gly Gly 235 Pro Ser Val Phe Leu 240 Phe Pro Pro Lys Pro 245 Lys Asp Thr Leu Met 250 Ile Ser Arg Thr Pro 255 Glu Val Thr Cys Val 260 Val Val Asp Val Ser 265 Gln Glu Asp Pro Glu 270 Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

- 557 044746

275

280

285

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

290 295300

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

305 310 315320

Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys

325 330335

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

340 345350

Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

355 360365

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

370 375380

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

385 390 395400

Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln

405 410415

Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

420 425430

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440445 <210>701 <211>1341 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 701 caggtgcagc tcctgtgcag ccaggcaagg gcagactccg ctgcaaatga gactacggtg tggtggagtc cctctggatt ggctggagtg tgaagggccg acagcctgag actacttatt tgggggaggc caccttcagt ggtggcagtt attcaccatc aactga ggac ggtttactgg gtggtccagc aactatgcta atatcatatg tccagagaca acggctgtgt ggccagggaa ctgggaggtc tgtactgggt atggaagtaa attccaagaa attactgtgc ccctggtcac cctgagactc ccgccaggct taaatactat cacgctgtat gagtggctcc cgtctcctca

120

180

240

300

360

- 558 044746

gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 420 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacgaagacc 600 tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 660 aaatatggtc ccccatgccc accgtgccca gcaccaggcg gtggcggacc atcagtcttc 720 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 780 gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 840 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cagtaccgt 900 gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 960 aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1020 cagccccgag agccacaggt gtacaccctg ccccatccc aggaggat gaccaagaac 1080 caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1140 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1200 ggctccttct tcctctacag caggctcacc gtggacaaga gcaggtggca ggaggggaat 1260 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagtccctc 1320 tccctgtctc tgggtaaatg a 1341

<210> 702 <211> 446 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 702

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Ser Asn Tyr 25 30

Ala Met Tyr Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ala Val Ile Ser Tyr Asp Gly Ser

55

Asn Lys Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg

Asp Asn Ser Lys Asn Thr Leu Tyr

- 559 044746

Leu Gln Met Asn Ser

Leu Arg Thr Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Ser Gly Ser Asp

100

Tyr Gly Asp Tyr Leu

105

Leu Val Tyr Trp Gly

110

Gly Thr Leu Val Thr 115

Val Ser Ser Ala Ser

120

Thr Lys Gly Pro Ser

125

Phe Pro Leu Ala Pro

130

Cys Ser Arg Ser Thr

135

Ser Glu Ser Thr Ala

140

Leu Gly Cys Leu Val 145

Lys Asp Tyr Phe Pro 150

Glu Pro Val Thr Val 155

Trp Asn Ser Gly Ala

165

Leu Thr Ser Gly Val

170

His Thr Phe Pro Ala

175

Leu Gln Ser Ser Gly

180

Leu Tyr Ser Leu Ser

185

Ser Val Val Thr Val

190

Ser Ser Ser Leu Gly 195

Thr Lys Thr Tyr Thr 200

Cys Asn Val Asp His

205

Pro Ser Asn Thr Lys 210

Val Asp Lys Arg Val

215

Glu Ser Lys Tyr Gly 220

Pro Cys Pro Pro Cys 225

Pro Ala Pro Gly Gly 230

Gly Gly Pro Ser Val 235

Leu Phe Pro Pro Lys

245

Pro Lys Asp Thr Leu

250

Met Ile Ser Arg Thr

255

Glu Val Thr Cys Val

260

Val Val Asp Val Ser

265

Gln Glu Asp Pro Glu

270

Gln Phe Asn Trp Tyr

275

Val Asp Gly Val Glu

280

Val His Asn Ala Lys

285

Lys Pro Arg Glu Glu

290

Gln Phe Asn Ser Thr

295

Tyr Arg Val Val Ser

300

Leu Thr Val Leu His 305

Gln Asp Trp Leu Asn 310

Gly Lys Glu Tyr Lys 315

Cys

Gln

Val

Ala

Ser 160

Val

Pro

Lys

Pro

Phe 240

Pro

Val

Thr

Val

Cys 320

- 560 044746

Lys Val

Ser Asn

Lys Ala

Lys Gly

340

Ser Gln

Glu Glu 355

Lys Gly

370

Phe Tyr

Gln Pro 385

Glu Asn

Gly Ser

Phe Phe

Gln Glu

Gly Asn

420

Asn His

Tyr Thr 435

Lys Gly 325

Glin Pro

Met Thr

Pro Ser

Asn Tyr 390

Leu Tyr 405

Val Phe

Gln Lys

Leu Pro

Arg Glu

Lys Asn

360

Asp Ile 375

Lys Thr

Ser Arg

Ser Cys

Ser Leu

440

Ser Ser

330

Pro Gln 345

Gln Val

Ala Val

Thr Pro

Leu Thr

410

Ser Val

425

Ser Leu <210> 703 <211> 1362 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 703 gaggtgcagc tcctgtacag ccagggaagg tacgcagact tatctgcaaa ggcgatggta accacggtca tgctccagga cccgaaccgg ccggctgtcc agcagcttgg tggtggagtc cctctggatt ggctggagtg ctgtgaaggg tgaacagcct ccagctccct ccgtctcctc gcacctccga tgacggtgtc tacagtcctc gcacgaagac tgggggaggc caccttcagt ggtttcatac ccgattcacc gagagccgag aatccaccac agcctccacc gagcacagcc gtggaactca aggactctac ctacacctgc

Ile Glu

Val Tyr

Ser Leu

Glu Trp

380

Pro Val 395

Val Asp

Met His

Ser Leu ttggtacagc aattatgaaa attagtagta atctccagag gacacggctg tactactaca aagggcccat gccctgggct ggcgccctga tccctcagca aacgtagatc

Lys Thr

Thr Leu

350

Thr Cys 365

Glu Ser

Leu Asp

Lys Ser

Glu Ala

430

Gly Lys 445 ctggagggtc tgaactgggt ggagtggtag acaacgccaa tttattactg tggacgtctg cggtcttccc gcctggtcaa ccagcggcgt gcgtggtgac acaagcccag

Ile Ser 335

Pro Pro

Leu Val

Asn Gly

Ser Asp 400

Arg Trp 415

Leu His cctgagactc ccgccaggct taccctacac gaactcactg tgcgagaagg gggcaaaggg cctggcgccc ggactacttc gcacaccttc cgtgccctcc caacaccaag

120

180

240

300

360

420

480

540

600

660

- 561 044746 gtggacaaga ggtggcggac cggacccctg ttcaactggt cagttcaaca aacggcaagg accatctcca caggaggaga agcgacatcg cctcccgtgc agcaggtggc cactacacac gagttgagtc catcagtctt aggtcacgtg acgtggatgg gcacgtaccg a gtacaagtg aagccaaagg tgaccaagaa ccgtggagtg tggactccga aggaggggaa agaagtccct caaatatggt cctgttcccc cgtggtggtg cgtggaggtg tgtggtcagc caaggtctcc gcagccccga ccaggtcagc ggagagcaat cggctccttc tgtcttctca ctccctg tct cccccatgcc ccaaaaccca gacgtgagcc cataatgcca gtcctcaccg aacaaaggcc gagccacagg ctgacctgcc gggcagccgg ttcctctaca tgctccgtga ctgggtaaat caccgtgccc aggacactct aggaagaccc agacaaagcc tcctgcacca tcccgtcctc tgtacaccct tggtcaaagg agaacaacta gcaggctcac tgcatgaggc ga agcaccaggc catgatctcc cgaggtccag gcgggaggag ggactggctg catcgagaaa gcccccatcc cttct acccc caagaccacg cgtggacaag tctgcacaac

720

780

840

900

960

1020

1080

1140

1200

1260

1320

1362 <210> 704 <211> 453 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 704

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Thr Ala 20

Ser Gly Phe Thr Phe Ser Asn Tyr 25 30

Glu Met Asn Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Tyr Ile Ser Ser Arg Ser Gly

55

Ser Thr Leu His Tyr Ala Asp Ser 60

Val Lys Gly Arg Phe Thr Ile Ser 65 70

Arg Asp Asn Ala Lys Asn Ser Leu

80

Tyr Leu Gln Met Asn Ser Leu Arg 85

Ala Glu Asp Thr Ala Val Tyr Tyr

95

Cys Ala Arg Arg Gly Asp Gly Thr

100

Ser Ser Leu Ile His His Tyr Tyr

105 110

- 562 044746

Tyr

Ser

Thr 145

Pro

Val

Ser

Thr

Val 225

Gly

Leu

Ser

Glu

Thr 305

Asn

Ser

Gln

Met Asp Val

115

Thr Lys Gly 130

Ser Glu Ser

Glu Pro Val

His Thr Phe

180

Ser Val Val

195

Cys Asn Val 210

Glu Ser Lys

Gly Gly Pro

Met Ile Ser

260

Gln Glu Asp

275

Val His Asn 290

Tyr Arg Val

Gly Lys Glu

Ile Glu Lys

340

Val Tyr Thr

355

Trp Gly Lys

Gly Thr Thr 120

Val Thr Val

125

Ser Ser Ala

Pro Ser Val

135

Phe Pro Leu

Ala Pro Cys

140

Ser Arg Ser

Thr Ala Ala

150

Thr Val Ser 165

Pro Ala Val

Thr Val Pro

Asp His Lys

215

Tyr Gly Pro

230

Ser Val Phe 245

Arg Thr Pro

Pro Glu Val

Ala Lys Thr

295

Val Ser Val

310

Tyr Lys Cys 325

Thr Ile Ser

Leu Pro Pro

Leu Gly Cys

Leu Val Lys 155

Asp Tyr Phe

160

Trp Asn Ser

170

Leu Gln Ser

185

Ser Ser Ser 200

Pro Ser Asn

Pro Cys Pro

Leu Phe Pro

250

Glu Val Thr

265

Gln Phe Asn 280

Lys Pro Arg

Leu Thr Val

Lys Val Ser

330

Lys Ala Lys

345

Ser Gln Glu 360

Gly Ala Leu

Thr Ser Gly

175

Ser Gly Leu

Tyr Ser Leu 190

Leu Gly Thr

205

Thr Lys Val

220

Pro Cys Pro 235

Pro Lys Pro

Cys Val Val

Trp Tyr Val

285

Glu Glu Gln

300

Leu His Gln 315

Asn Lys Gly

Gly Gln Pro

Glu Met Thr

365

Lys Thr Tyr

Asp Lys Arg

Ala Pro Gly

240

Lys Asp Thr

255

Val Asp Val 270

Asp Gly Val

Phe Asn Ser

Asp Trp Leu

320

Leu Pro Ser

335

Arg Glu Pro 350

Lys Asn Gln

- 563 044746

Val

Ser

370

Leu

Thr

Cys

Leu

Val

375

Lys

Gly

Phe

Tyr

Pro

380

Ser

Asp

Ile

Ala

Val

385

Glu

Trp

Glu

Ser

Asn

390

Gly

Gln

Pro

Glu

Asn

395

Asn

Tyr

Lys

Thr

Thr

400

Pro

Pro

Val

Leu

Asp

405

Ser

Asp

Gly

Ser

Phe

410

Phe

Leu

Tyr

Ser

Arg 415

Leu

Thr

Val

Asp

Lys 420

Ser

Arg

Trp

Gln

Glu

425

Gly

Asn

Val

Phe

Ser 430

Cys

Ser

Val

Met

His

435

Glu

Ala

Leu

His

Asn

440

His

Tyr

Thr

Gln

Lys 445

Ser

Leu

Ser

Leu Ser Leu Gly Lys

450

<210> 705 <211> 1350 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 705 caggtgcagc tggtgcagtc tggggctgag gtgaagaagc ctggggcctc agtgaaggtc 60 tcctgcaagg cttctggata catcttcacc ggctactata tgcactgggt gcgacaggcc 120 cctggacagg ggcttgagtg gatgggatgg atcaacccta acagtggtgg cgcaaactat 180 gcacagaagt ttcaggggcag ggtcaccctg accagggaca cgtccatcac cacagtctac 240 atggaactga gcaggctgag atttgacgac acggccgtgt attackgtgc gagaggatcc 300 cggtatgact ggaaccagaa caactggttc gacccctggg gccagggaac cctggtcacc 360 gtctcctcag cctccaccaa gggcccatcg gtcttccccc tggcgccctg ctccaggagc 420 acctccgaga gcacagccgc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 480 acggtgtcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 540 cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttggggc 600 acgaagacct acacctgcaa cgtagatcac aagccagca acaccaaggt ggacaagaga 660 gttgagtcca aatatggtcc cccatgccca ccgtgcccag caccaggcgg tggcggacca 720 tcagtcttcc tgttcccccc aaaacccaag gacactctca tgatctcccg gacccctgag 780 gtcacgtgcg tggtggtgga cgtgagccag gaagaccccg aggtccagtt caactggtac 840 gtggatggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gttcaacagc 900

- 564 044746 acgtaccgtg tacaagtgca gccaaagggc accaagaacc gtggagtggg gactccgacg gaggggaatg aagtccctct tggtcagcgt aggtctccaa agccccgaga aggtcagcct agagcaatgg gctccttctt tcttctcatg ccctgtctct cctcaccgtc ca aaggcctc gccacaggtg gacctgcctg gcagccggag cctctacagc ctccgtgatg gggtaaatga ctgcaccagg ccgtcctcca tacaccctgc gtcaaaggct aacaactaca aggctcaccg catgaggctc actggctgaa tcgagaaaac ccccatccca tctaccccag agaccacgcc tggacaagag t gcacaacca cggcaaggag catctccaaa ggagagatg cgacatcgcc tcccgtgctg caggtggcag ctacacacag

960

1020

1080

1140

1200

1260

1320

1350 <210> 706 <211> 449 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 706

Gln Val Gln Leu Val Gln Ser Gly 1 5

Ala Glu Val Lys Lys Pro Gly Ala

15

Ser Val Lys Val Ser Cys Lys Ala 20

Ser Gly Tyr Ile Phe Thr Gly Tyr 25 30

Tyr Met His Trp Val Arg Gln Ala

40

Pro Gly Gln Gly Leu Glu Trp Met 45

Gly Trp Ile Asn Pro Asn Ser Gly

55

Gly Ala Asn Tyr Ala Gln Lys Phe 60

Gln Gly Arg Val Thr Leu Thr Arg 65 70

Asp Thr Ser Ile Thr Thr Val Tyr

80

Met Glu Leu Ser Arg Leu Arg Phe 85

Asp Asp Thr Ala Val Tyr Tyr Cys

95

Ala Arg Gly Ser Arg Tyr Asp Trp

100

Asn Gln Asn Asn Trp Phe Asp Pro

105 110

Trp Gly Gln Gly Thr Leu Val Thr

115 120

Val Ser Ser Ala Ser Thr Lys Gly

125

Pro Ser Val Phe Pro Leu Ala Pro

130 135

Cys Ser Arg Ser Thr Ser Glu Ser

140

- 565 044746

Thr Ala Ala Leu Gly Cys

145 150

Leu Val Lys Asp Tyr Phe Pro Glu Pro

155

Thr Val Ser Trp Asn Ser 165

Pro Ala Val Leu Gln Ser 180

Thr Val Pro Ser Ser Ser 195

Asp His Lys Pro Ser Asn 210

Gly Ala Leu Thr Ser Gly Val His Thr

170 175

Ser Gly Leu Tyr Ser Leu Ser Ser Val

185 190

Leu Gly Thr Lys Thr Tyr Thr Cys Asn

200 205

Thr Lys Val Asp Lys Arg Val Glu Ser

215 220

Tyr Gly Pro 225

Ser Val Phe

Pro Cys

Pro Pro Cys Pro Ala Pro Gly Gly Gly Gly

230 235

Arg Thr Pro

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val 305

Tyr Lys Cys

Thr Ile Ser

Leu Pro Pro

355

Cys Leu Val

370

Ser Asn Gly 385

Leu Phe

245

Glu Val

260

Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

250 255

Thr Cys Val Val Val Asp Val Ser Gln Glu

265 270

Gln Phe Asn Trp Tyr Val Asp Gly Val

280

Lys Pro Arg Glu Glu

295

Leu Thr Val Leu His

310

Lys Val Ser Asn Lys

325

Lys Ala Lys Gly Gln 340

Ser Gln Glu Glu Met

360

Lys Gly Phe Tyr Pro

375

Gln Pro Glu Asn Asn

390

Glu Val His 285

Gln Phe Asn Ser Thr Tyr Arg 300

Gln Asp Trp Leu Asn Gly Lys 315

Gly Leu Pro Ser Ser Ile Glu

330 335

Pro Arg Glu Pro Gln Val Tyr

345 350

Thr Lys Asn Gln Val Ser Leu 365

Ser Asp Ile Ala Val Glu Trp 380

Tyr Lys Thr Thr Pro Pro Val 395

Val 160

Phe

Val

Val

Lys

Pro 240

Ser

Asp

Asn

Val

Glu 320

Lys

Thr

Thr

Glu

Leu 400

- 566 044746

Asp Ser Asp Gly Ser Phe Phe Leu Tyr 405

Ser Arg Trp Gln Glu Gly Asn Val Phe

420 425

Ser Arg

410

Ser Cys

Leu Thr Val Asp Lys

415

Ser Val Met His Glu

430

Ala Leu His Asn His Tyr Thr Gln Lys

435 440

Ser Leu

Ser Leu Ser Leu Gly 445

Lys

707

351

DNA

Artificial

Synthetic

707 <210>

<211>

<212> <213>

<220> <223>

<400>

gaggtgcaga tcctgtgcag ccagggaagg gactccgtga caaatgaaca tcctacggta sequence tggtggagtc cctctgggtt ggctggagtg agggccgatt gcctgagagc tggacgtctg tggaggaggc caccgtcagt ggtctcagtt caccatctcc tgaggacacg gggccaaggg ttgg tccagc agtaactaca atttatagcg agacacaatt gccgtgtatt accacggtca ctggggggtc tgacctgggt gtggtagcac ccaagaacac actgtgcgag ccgtctcctc cctgagactc ccgccaggct atactacgca gctgtatctt agatggggta a

120

180

240

300

351 <210> 708 <211> 117 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 708

Glu Val Gln Met Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Val Ser Ser Asn 25 30

Tyr Met Thr Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Ser Gly Gly Ser

Thr Tyr Tyr Ala Asp Ser Val Lys

- 567 044746

Gly Arg 65

Gln Met

Arg Asp

Phe Thr

Asn Ser

Gly Val

100

Ile Ser

Leu Arg 85

Ser Tyr

Arg His

Asn Ser

Ala Glu

Asp Thr

Gly Met

Asp Val 105

Lys Asn 75

Ala Val

Trp Gly

Thr Leu

Tyr Tyr

Gln Gly

110

Tyr Leu 80

Cys Ala 95

Thr Thr

Val Thr Val Ser Ser

115 <210> 709 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>709 gggttcaccg tcagtagtaa ctac <210>710 <211>33 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>710 gcgagagatg gggtatccta cggtatggac gtc <210>711 <211>11 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>711

Ala Arg Asp Gly Val Ser Tyr Gly Met Asp Val

510 <210>712 <211>324 <212> DNA <213> Artificial sequence <220>

- 568 044746 <223> Synthetic <400> 712

gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccgtca 180 aggttcagtg gcagtggatc tggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagatttg caactacta ctgtcaacag agttacagta cccctccgat caccttcggc 300 caagggacac gactggagat taaa 324

<210> 713 <211> 108 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 713

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg 20

Ala Ser Gln Ser Ile Ser Ser Tyr 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro

40

Gly Lys Ala Pro Lys Leu Leu Ile 45

Tyr Ala Ala Ser Ser Leu Gln Ser

55

Gly Val Pro Ser Arg Phe Ser Gly 60

Ser Gly Ser Gly Thr Asp Phe Thr 65 70

Leu Thr Ile Ser Ser Leu Gln Pro

80

Glu Asp Phe Ala Thr Tyr Tyr Cys 85

Gln Gln Ser Tyr Ser Thr Pro Pro

95

Ile Thr Phe Gly Gln Gly Thr Arg

100

Leu Glu Ile Lys 105 <210> 714 <211> 30 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic < 400> 714

- 569 044746 caacagagtt acagtacccc tccgatcacc <210> 715 <211> 10 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>715

Gln Gln Ser Tyr Ser Thr Pro Pro Ile Thr

510 <210>716 <211>1344 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 716 gaggtgcaga tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt caccgtcagt agtaactaca tgacctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatggggta 300 tcctacggta tggacgtctg gggccaaggg accacggtca ccgtctcctc agcctccacc 360 aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc 600 aacgtgaatc acaagcccag caacaccaag gtggacaaga aagttgagcc caaatcttgt 660 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 720 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 780 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 840 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 900 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 960 tgcaaggtct ccaacaaagc cctcccagcc ccatcgaga aaaccatctc caaagccaaa 1020 gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 1080 aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1140

- 570 044746 tgggagagca gacggctcct aacgtcttct ctctccctgt atgggcagcc tcttcctcta catgctccgt ctccgggtaa ggagaacaac cagcaagctc gatgcatgag atga tacaagacca accgtggaca gctctgcaca cgcctcccgt agagcaggtg accactacac gctggactcc gcagcagggg gcagaagtcc

1200

1260

1320

1344 <210> 717 <211> 447 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 717

Glu Val 1

Gln Met

Val Glu 5

Ser Gly

Gly Gly 10

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Tyr Met

Thr Trp 35

Val Arg

Gln Ala

Pro Gly

Ser Val

Ile Tyr

Ser Gly

Gly Ser 55

Thr Tyr

Gly Arg 65

Phe Thr

Ile Ser

Arg His

Asn Ser

Gln Met

Asn Ser

Leu Arg 85

Ala Glu

Asp Thr

Arg Asp

Gly Val

100

Ser Tyr

Gly Met

Asp Val 105

Val Thr

Val Ser

115

Ser Ala

Ser Thr

120

Lys Gly

Ala Pro

130

Ser Ser

Lys Ser

Thr Ser 135

Gly Gly

Leu Val

Phe Thr

Lys Gly

Tyr Ala 60

Lys Asn 75

Ala Val

Trp Gly

Pro Ser

Thr Ala 140

Glin Pro

Val Ser

Leu Glu 45

Asp Ser

Gly Gly 15

Ser Asn

Trp Val

Val Lys

Thr Leu

Tyr Tyr

Gln Gly

110

Val Phe 125

Ala Leu

Tyr Leu 80

Cys Ala 95

Thr Thr

ProLeu

Gly Cys

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

145 150 155 160

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

165 170 175

- 571 044746

Ser

Leu

Thr

Thr 225

Phe

Pro

Val

Thr

Val 305

Cys

Ser

Pro

Val

Gly 385

Asp

Trp

Gly Leu Tyr

180

Gly Thr Gln

195

Lys Val Asp 210

Cys Pro Pro

Leu Phe Pro

Glu Val Thr

260

Lys Phe Asn

275

Lys Pro Arg 290

Leu Thr Val

Lys Val Ser

Lys Ala Lys

340

Ser Arg Asp

355

Lys Gly Phe 370

Gln Pro Glu

Gly Ser Phe

Gln Gln Gly

420

Ser Leu Ser

Thr Tyr Ile

Lys Lys Val

215

Cys Pro Ala

230

Pro Lys Pro 245

Cys Val Val

Trp Tyr Val

Glu Glu Gln

295

Leu His Gln

310

Asn Lys Ala 325

Gly Gln Pro

Glu Leu Thr

Tyr Pro Ser

375

Asn Asn Tyr

390

Phe Leu Tyr 405

Asn Val Phe

Ser Val Val

185

Cys Asn Val 200

Glu Pro Lys

Pro Glu Leu

Lys Asp Thr

250

Val Asp Val

265

Asp Gly Val 280

Tyr Asn Ser

Asp Trp Leu

Leu Pro Ala

330

Arg Glu Pro

345

Lys Asn Gln 360

Asp Ile Ala

Lys Thr Thr

Ser Lys Leu

410

Ser Cys Ser

425

Thr Val Pro

Ser Ser Ser 190

Asn His Lys

205

Pro Ser Asn

Ser Cys Asp

220

Leu Gly Gly 235

Leu Met Ile

Ser His Glu

Glu Val His

285

Thr Tyr Arg

300

Asn Gly Lys 315

Pro Ile Glu

Gln Val Tyr

Val Ser Leu

365

Val Glu Trp

380

Pro Pro Val 395

Thr Val Asp

Val Met His

Lys Thr His

Pro Ser Val

240

Ser Arg Thr

255

Asp Pro Glu 270

Asn Ala Lys

Val Val Ser

Glu Tyr Lys

320

Lys Thr Ile

335

Thr Leu Pro 350

Thr Cys Leu

Glu Ser Asn

Leu Asp Ser

400

Lys Ser Arg

415

Glu Ala Leu 430

- 572 044746

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440445 <210>718 <211>648 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 718 gacatccaga atcacttgcc gggaaagccc aggttcagtg gaagattttg caagggacac ccatctgatg tatcccagag caggagagtg acgctgagca ggcctgagct tgacccagtc gggcaagtca ctaagctcct gcagtggatc caacttacta gactggagat agcagttgaa aggccaaagt tcacagagca aagcagacta cgcccgtcac tccatcctcc gagcattagc gatctatgct tgggacagat ctgtcaacag taaacgaact atctggaact acagtggaag ggacagcaag cgagaaacac aaagagcttc ctgtctgcat agctatttaa gcatccagtt ttcact ctca agttacagta gtggctgcac gcctctgttg gtggataacg gacagcacct aaagtctacg aacaggggag ctgtaggaga attggtatca tgcaaagtgg ccatcagcag cccctccgat catctgtctt tgtgcctgct ccctccaatc acagcctcag cctgcgaagt agtgttag cagagtcacc gcagaaacca ggtcccgtca tctgcaacct caccttcggc catcttcccg gaataacttc gggtaactcc cagcaccctg cacccatcag

120

180

240

300

360

420

480

540

600

648 <210> 719 <211> 215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>719

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

- 573 044746

Ser Gly 65

Glu Asp

Ile Thr

Ala Pro

Gly Thr 130

Ala Lys 145

Gln Glu

Ser Ser

Tyr Ala

Ser Gly

Phe Ala

Phe Gly

100

Ser Val 115

Ala Ser

Val Gln

Ser Val

Thr Leu

180

Cys Glu 195

Thr Asp 70

Thr Tyr 85

Gln Gly

Phe Ile

Val Val

Trp Lys

150

Thr Glu 165

Thr Leu

Val Thr

Ser Phe Asn Arg Gly Glu

210

720

1332

DNA

Artificial

Synthetic

720 <210>

<211>

<212> <213>

<220> <223>

<400>

gaggtgcaga tcctgtgcag ccagggaagg gactccgtga caaatgaaca tcctacggta aagggcccat

Phe Thr

Tyr Cys

Thr Arg

Phe Pro

120

Cys Leu 135

Val Asp

Gln Asp

Ser Lys

His Gln

200

Cys 215

Leu Thr

Gln Gln

Leu Glu 105

Pro Ser

Leu Asn

Asn Ala

Ser Lys

170

Ala Asp 185

Gly Leu sequence tggtggagtc cctctgggtt ggctggagtg agggccgatt gcctgagagc tggacgtctg cggtcttccc tggaggaggc caccgtcagt ggtctcagtt caccatctcc tgaggacacg gggccaaggg cctggcgccc

Ile Ser 75

Ser Tyr

Ile Lys

Asp Glu

Asn Phe

140

Leu Gln 155

Asp Ser

Tyr Glu

Ser Ser ttggtccagc agtaactaca atttatagcg agacacaatt gccgtgtatt accacggtca tgctccagga

Ser Leu

Ser Thr

Arg Thr

110

Gln Leu 125

Tyr Pro

Ser Gly

Thr Tyr

Lys His

190

Pro Val 205 ctggggggtc tgacctgggt gtggtagcac ccaagaacac actgtgcgag ccgtctcctc gcacctccga

Glin Pro

Pro Pro 95

Val Ala

Lys Ser

Arg Glu

Asn Ser

160

Ser Leu 175

Lys Val

Thr Lys cctgagactc ccgccaggct atactacgca gctgtatctt agatggggta agcctccacc gagcacagcc

120

180

240

300

360

420

- 574 044746

gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctacacctgc 600 aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt 660 ccccatgcc caccgtgccc agcaccaggc ggtggcggac catcagtctt cctgttcccc 720 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg 780 gacgtgagcc aggaagacc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 840 cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 900 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 960 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1020 gagccacagg tgtacaccct gcccccatcc caggagaga tgaccaagaa ccaggtcagc 1080 ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1140 gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc 1200 ttcctctaca gcaggctcac cgtggacaag agcaggtggc aggaggggaa tgtcttctca 1260 tgctccgtga tgcatgaggc tctgcacaac cactacacac agaagtccct ctccctgtct 1320 ctgggtaaat ga 1332

<210> 721 <211> 443 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>721

Glu Val Gln Met Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn 20 2530

Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

- 575 044746

Gln

Arg

Val

Ala

Leu 145

Gly

Ser

Leu

Thr

Pro 225

Pro

Cys

Trp

Glu

Leu 305

Asn

Met Asn Ser

Asp Gly Val

100

Thr Val Ser

115

Pro Cys Ser 130

Val Lys Asp

Ala Leu Thr

Gly Leu Tyr

180

Gly Thr Lys

195

Lys Val Asp 210

Cys Pro Ala

Lys Pro Lys

Val Val Val

260

Tyr Val Asp

275

Glu Gln Phe 290

His Gln Asp

Lys Gly Leu

Leu Arg Ala 85

Ser Tyr Gly

Ser Ala Ser

Arg Ser Thr

135

Tyr Phe Pro

150

Ser Gly Val 165

Ser Leu Ser

Thr Tyr Thr

Lys Arg Val

215

Pro Gly Gly

230

Asp Thr Leu 245

Asp Val Ser

Gly Val Glu

Asn Ser Thr

295

Trp Leu Asn

310

Pro Ser Ser 325

Glu Asp Thr

Met Asp Val

105

Thr Lys Gly 120

Ser Glu Ser

Glu Pro Val

His Thr Phe

170

Ser Val Val

185

Cys Asn Val 200

Glu Ser Lys

Gly Gly Pro

Met Ile Ser

250

Gln Glu Asp

265

Val His Asn 280

Tyr Arg Val

Gly Lys Glu

Ile Glu Lys

330

Ala Val Tyr

Trp Gly Gln

Pro Ser Val

125

Thr Ala Ala

140

Thr Val Ser 155

Pro Ala Val

Thr Val Pro

Asp His Lys

205

Tyr Gly Pro

220

Ser Val Phe 235

Arg Thr Pro

Pro Glu Val

Ala Lys Thr

285

Val Ser Val

300

Tyr Lys Cys 315

Thr Ile Ser

Tyr Cys Ala 95

Gly Thr Thr 110

Phe Pro Leu

Leu Gly Cys

Trp Asn Ser

160

Leu Gln Ser

175

Ser Ser Ser 190

Pro Ser Asn

Pro Cys Pro

Leu Phe Pro

240

Glu Val Thr

255

Gln Phe Asn 270

Lys Pro Arg

Leu Thr Val

Lys Val Ser

320

Lys Ala Lys

335

- 576 044746

Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu

340 345350

Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe

355 360365

Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu

370 375380

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

385 390 395400

Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly

405 410415

Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr

420 425430

Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435440 <210>722 <211>357 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 722

gaggtgcagc tggtggagtc tggaggaggc ttggtccacc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggct caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtttctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatcggcca 300 ataactggaa ccactttgga cgtctggggc caagggacca cggtcaccgt ctcctca 357

<210> 723 <211> 119 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 723

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val His Pro Gly Gly

- 577 044746

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Leu Thr Val Ser Ser Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Phe Leu 65 70 7580

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

Arg Asp Arg Pro Ile Thr Gly Thr Thr Leu Asp Val Trp Gly Gln Gly

100 105110

Thr Thr Val Thr Val Ser Ser

115 <210>724 <211>39 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>724 gcgagagatc ggccaataac tggaaccact ttggacgtc <210>725 <211>13 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>725

Ala Arg Asp Arg Pro Ile Thr Gly Thr Thr Leu Asp Val

510 <210>726 <211>324 <212> DNA <213> Artificial sequence <220>

- 578 044746 <223> Synthetic <400> 726

gacatccaga tgaccagtc tccatcctcc ctgtttgcat ctgtagggga cagagtcacc 60 atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180 aggttcagtg gcagtggatc tggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagatttg catttacta ctgtcaacag acttacagta cccctccgat caccttcggc 300 caagggacac gactggagat taaa 324

<210> 727 <211> 108 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 727

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

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg 20

Ala Ser Gln Ser Ile Ser Ser Tyr 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro

40

Gly Lys Ala Pro Lys Leu Leu Ile 45

Tyr Ala Ala Ser Ser Leu Gln Ser

55

Gly Val Pro Ser Arg Phe Ser Gly 60

Ser Gly Ser Gly Thr Asp Phe Thr 65 70

Leu Thr Ile Ser Ser Leu Gln Pro

80

Glu Asp Phe Ala Phe Tyr Tyr Cys 85

Gln Gln Thr Tyr Ser Thr Pro Pro

95

Ile Thr Phe Gly Gln Gly Thr Arg

100

Leu Glu Ile Lys 105 <210> 728 <211> 30 <212> DNA <213> Artificial sequence <220>

< 223> Synthetic < 400> 728

- 579 044746 caacagactt acagtacccc tccgatcacc <210> 729 <211> 10 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>729

Gln Gln Thr Tyr Ser Thr Pro Pro Ile Thr

510 <210>730 <211>1350 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 730 gaggtgcagc tggtggagtc tggaggaggc ttggtccacc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggct caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtttctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatcggcca 300 ataactggaa ccactttgga cgtctggggc caagggacca cggtcaccgt ctcctcagcc 360 tccaccaagg gcccatcggt cttccccctg gcaccctcct ccaagagcac ctctggggggc 420 acaggccc tggggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac ccagacctac 600 atctgcaacg tgaatcacaa gccagcaac accaaggtgg acaagaaagt tgagcccaaa 660 tcttgtgaca aaactcacac atgcccaccg tgcccagcac ctgaactcct ggggggaccg 720 tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780 gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840 gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacaacagc 900 acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaagggag 960 tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1020 gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1080 accaagaacc aggtcagcct gacctgcctg gtcaaaggct tctatcccag cgacatcgcc 1140

- 580 044746 gtggagtggg gactccgacg caggggaacg aagtccctct agagcaatgg gctccttctt tcttctcatg ccctgtctcc gcagccggag cctctacagc ctccgtgatg gggtaaatga aacaactaca aagctcaccg catgaggctc agaccacgcc tggacaagag tgcaca acca tcccgtgctg caggtggcag ctacacgcag

1200

1260

1320

1350 <210> 731 <211> 449 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 731

Glu Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly 10

Leu Val

His Pro

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Leu Thr

Val Ser

Tyr Met

Ser Trp 35

Val Arg

Gln Ala

Pro Gly

Lys Gly

Leu Glu 45

Ser Val

Ile Tyr

Ser Gly

Gly Ser 55

Thr Tyr

Tyr Ala 60

Asp Ser

Gly Gly 15

Ser Asn

Trp Val

Val Lys

Gly Arg 65

Phe Thr

Ile Ser

Arg His

Asn Ser

Lys Asn 75

Thr Leu

Phe Leu

Gln Met

Asn Ser

Leu Arg 85

Ala Glu

Asp Thr

Ala Val

Tyr Tyr

Cys Ala 95

Arg Asp

Arg Pro

100

Ile Thr

Gly Thr

Thr Leu 105

Asp Val

Trp Gly

110

Gln Gly

Thr Thr

Val Thr

115

Val Ser

Ser Ala

120

Ser Thr

Lys Gly

Pro Ser 125

Val Phe

ProLeu

130

Ala Pro

Ser Ser

Lys Ser 135

Thr Ser

Gly Gly

140

Thr Ala

Ala Leu

Gly Cys 145

Leu Val

Lys Asp

150

Tyr Phe

Pro Glu

Pro Val 155

Thr Val

Ser Trp

160

Asn Ser

Gly Ala

Leu Thr 165

Ser Gly

Val His

170

Thr Phe

Pro Ala

Val Leu

175

- 581 044746

Gln

Ser

Ser

Thr 225

Ser

Arg

Pro

Ala

Val 305

Tyr

Thr

Leu

Cys

Ser 385

Asp

Ser

Ser Ser Gly

180

Ser Leu Gly

195

Asn Thr Lys 210

His Thr Cys

Val Phe Leu

Thr Pro Glu

260

Glu Val Lys

275

Lys Thr Lys 290

Ser Val Leu

Lys Cys Lys

Ile Ser Lys

340

Pro Pro Ser

355

Leu Val Lys 370

Asn Gly Gln

Ser Asp Gly

Arg Trp Gln

420

Leu Tyr Ser

Thr Gln Thr

Val Asp Lys

215

Pro Pro Cys

230

Phe Pro Pro 245

Val Thr Cys

Phe Asn Trp

Pro Arg Glu

295

Thr Val Leu

310

Val Ser Asn 325

Ala Lys Gly

Arg Asp Glu

Gly Phe Tyr

375

Pro Glu Asn

390

Ser Phe Phe 405

Gln Gly Asn

Leu Ser Ser

185

Tyr Ile Cys 200

Lys Val Glu

Pro Ala Pro

Lys Pro Lys

250

Val Val Val

265

Tyr Val Asp 280

Glu Gln Tyr

His Gln Asp

Lys Ala Leu

330

Gln Pro Arg

345

Leu Thr Lys 360

Pro Ser Asp

Asn Tyr Lys

Leu Tyr Ser

410

Val Phe Ser

425

Val Val Thr

Asn Val Asn

205

Pro Lys Ser

220

Glu Leu Leu 235

Asp Thr Leu

Asp Val Ser

Gly Val Glu

285

Asn Ser Thr

300

Trp Leu Asn 315

Pro Ala Pro

Glu Pro Gln

Asn Gln Val

365

Ile Ala Val

380

Thr Thr Pro 395

Lys Leu Thr

Cys Ser Val

Val Pro Ser 190

His Lys Pro

Cys Asp Lys

Gly Gly Pro

240

Met Ile Ser

255

His Glu Asp 270

Val His Asn

Tyr Arg Val

Gly Lys Glu

320

Ile Glu Lys

335

Val Tyr Thr 350

Ser Leu Thr

Glu Trp Glu

Pro Val Leu

400

Val Asp Lys

415

Met His Glu 430

- 582 044746

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

Ser Leu Ser Pro Gly

435 440445

Lys <210>732 <211>648 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 732 gacatccaga tgaccagtc tccatcctcc ctgtttgcat ctgtagggga cagagtcacc 60 atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180 aggttcagtg gcagtggatc tggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagatttg catttacta ctgtcaacag acttacagta cccctccgat caccttcggc 300 caagggacac gactggagat taaacgaact gtggctgcac catctgtctt catcttcccg 360 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420 tatccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 648

<210>733 <211>215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 733

Asp Ile Gln Met

Thr Gln Ser Pro 5

Ser Ser Leu Phe

Ala Ser Val Gly

Asp Arg Val Thr

Ile Thr Cys Arg

Ala Ser Gln Ser 25

Ile Ser Ser Tyr 30

Leu Asn Trp Tyr

Gln Gln Lys Pro 40

Gly Lys Ala Pro

Lys Leu Leu Ile 45

- 583 044746

Tyr Ala 50

Ser Gly 65

Glu Asp

Ile Thr

Ala Pro

Ala Ser

Ser Gly

Phe Ala

Phe Gly

100

Ser Val 115

Ser Leu

Thr Asp 70

Phe Tyr 85

Gln Gly

Phe Ile

Gly Thr

130

Ala Ser

Val Val

Ala Lys 145

Val Gln

Trp Lys

150

Gln Glu

Ser Val

Thr Glu 165

Ser Ser

Thr Leu

180

Thr Leu

Tyr Ala

Cys Glu 195

Val Thr

Ser Phe Asn Arg Gly Glu

210

Gln Ser 55

Phe Thr

Tyr Cys

Thr Arg

Phe Pro

120

Cys Leu 135

Val Asp

Gln Asp

Ser Lys

His Gln

200

Cys 215

Gly Val

Leu Thr

Gln Gln

Leu Glu 105

Pro Ser

Leu Asn

Asn Ala

Ser Lys

170

Ala Asp 185

Gly Leu <210> 734 <211> 1338 <212> DNA <213> Artificial sequence

Synthetic

734 <220>

<223>

<400>

gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca tggtggagtc cctctgggct ggctggagtg agggccgatt gcctgagagc tggaggaggc caccgtcagt ggtctcagtt caccatctcc tgaggacacg

Pro Ser

Ile Ser 75

Thr Tyr

Ile Lys

Asp Glu

Asn Phe

140

Leu Gln 155

Asp Ser

Tyr Glu

Ser Ser ttggtccacc agcaactaca atttatagcg agacacaatt gccgtgtatt

Arg Phe

Ser Leu

Ser Thr

Arg Thr

110

Gln Leu 125

Tyr Pro

Ser Gly

Thr Tyr

Lys His

190

Pro Val 205 ctggggggtc tgagctgggt gtggtagcac ccaagaacac actgtgcgag

Ser Gly

Glin Pro

Pro Pro 95

Val Ala

Lys Ser

Arg Glu

Asn Ser

160

Ser Leu 175

Lys Val

Thr Lys cctgagactc ccgccaggct atactacgca gctgtttctt agatcggcca

120

180

240

300

- 584 044746

ataactggaa ccactttgga cgtctggggc caagggacca cggtcaccgt ctcctcagcc 360 tccaccaagg gcccatcggt cttccccctg gcgccctgct ccaggagcac ctccgagagc 420 acagccgccc tggggctgcct ggtcaaggac tacttccccg aaccggtgac ggtgtcgtgg 480 aactcaggcg ccctgaccag cggcgtgcac accttcccgg ctgtcctaca gtcctcagga 540 ctctactccc tcagcagcgt ggtgaccgtg ccctccagca gcttggggcac gaagacctac 600 acctgcaacg tagatcacaa gccagcaac accaaggtgg acaagagt tgagtccaaa 660 tatggtcccc catgcccacc gtgccagca ccaggcggtg gcggaccatc agtcttcctg 720 ttccccccaa aacccaagga cactctcatg atctcccgga cccctgaggt cacgtgcgtg 780 gtggtggacg tgagccagga agaccccgag gtccagttca actggtacgt ggatggcgtg 840 gaggtgcata atgccaagac aaagccgcgg gagggagt tcaacagcac gtaccgtgtg 900 gtcagcgtcc tcaccgtcct gcaccaggac tggctgaacg gcaagggagta caagtgcaag 960 gtctccaaca aaggcctccc gtcctccatc gagaaaacca tctccaaagc caaagggcag 1020 ccccgagagc cacaggtgta caccctgccc ccaccagg aggagatgac caagaaccag 1080 gtcagcctga cctgcctggt caaaggcttc taccccagcg acatcgccgt ggagtggggag 1140 agcaatggggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1200 tccttcttcc tctacagcag gctcaccgtg gacaagagca ggtggcagga ggggaatgtc 1260 ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacacagaa gtccctctcc 1320 ctgtctctgg gtaaatga 1338

<210> 735 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 735

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

His Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Leu Thr 25

Val Ser Ser Asn

Tyr Met Ser Trp

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Ser Val Ile Tyr 50

Ser Gly Gly Ser 55

Thr Tyr Tyr Ala 60

Asp Ser Val Lys

- 585 044746

Gly Arg Phe Thr Ile 65

Ser Arg His Asn Ser 70

Lys Asn Thr Leu Phe 75

Gln Met Asn Ser Leu

Arg Ala Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Asp Arg Pro Ile

100

Thr Gly Thr Thr Leu

105

Asp Val Trp Gly Gln

110

Thr Thr Val Thr Val

115

Ser Ser Ala Ser Thr

120

Lys Gly Pro Ser Val 125

Pro Leu Ala Pro Cys 130

Ser Arg Ser Thr Ser

135

Glu Ser Thr Ala Ala

140

Gly Cys Leu Val Lys 145

Asp Tyr Phe Pro Glu 150

Pro Val Thr Val Ser 155

Asn Ser Gly Ala Leu

165

Thr Ser Gly Val His

170

Thr Phe Pro Ala Val

175

Gln Ser Ser Gly Leu

180

Tyr Ser Leu Ser Ser

185

Val Val Thr Val Pro

190

Ser Ser Leu Gly Thr

195

Lys Thr Tyr Thr Cys 200

Asn Val Asp His Lys 205

Ser Asn Thr Lys Val

210

Asp Lys Arg Val Glu

215

Ser Lys Tyr Gly Pro

220

Cys Pro Pro Cys Pro 225

Ala Pro Gly Gly Gly 230

Gly Pro Ser Val Phe 235

Phe Pro Pro Lys Pro

245

Lys Asp Thr Leu Met

250

Ile Ser Arg Thr Pro

255

Val Thr Cys Val Val

260

Val Asp Val Ser Gln

265

Glu Asp Pro Glu Val

270

Phe Asn Trp Tyr Val

275

Asp Gly Val Glu Val 280

His Asn Ala Lys Thr

285

Pro Arg Glu Glu Gln 290

Phe Asn Ser Thr Tyr

295

Arg Val Val Ser Val

300

Thr Val Leu His Gln 305

Asp Trp Leu Asn Gly 310

Lys Glu Tyr Lys Cys 315

Leu 80

Ala

Gly

Phe

Leu

Trp 160

Leu

Ser

Pro

Pro

Leu 240

Glu

Gln

Lys

Leu

Lys 320

- 586 044746

Val Ser

Asn Lys

Ala Lys

Gly Gln

340

Gln Glu

Glu Met 355

Gly Phe

370

Tyr Pro

Pro Glu 385

Asn Asn

Ser Phe

Phe Leu

Glu Gly

Asn Val

420

His Tyr

Thr Gln 435

Gly Leu 325

Pro Arg

Thr Lys

Ser Asp

Tyr Lys 390

Tyr Ser 405

Phe Ser

Lys Ser

Pro Ser

Glu Pro

Asn Gln

360

Ile Ala

375

Thr Thr

Arg Leu

Cys Ser

Leu Ser

440

Ser Ile

330

Gln Val 345

Val Ser

Val Glu

Pro Pro

Thr Val

410

ValMet 425

Leu Ser <210> 736 <211> 351 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 736 gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca gcctacggta tggtggagtc cctctgggtt ggctggagtg ggggccgatt gcctgagagc tggacgtctg tggaggaggc caccgtcagt ggtctcagtt caccat ctcc tgaggacacg gggccaaggg

Glu Lys

Tyr Thr

Leu Thr

Trp Glu

380

Val Leu 395

Asp Lys

His Glu

Leu Gly ttggtccagc agcaactaca atttatagcg agacacaatt gccgtgtatt accacggtca <210> 737 <211> 117 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic

Thr Ile

Leu Pro

350

Cys Leu 365

Ser Asn

Asp Ser

Ser Arg

Ala Leu

430

Lys 445 ctggggggtc tgaactgggt gtggtagcac ccaagaacac actgtgcgag ccgtctcctc

Ser Lys 335

Pro Ser

Val Lys

Gly Gln

Asp Gly 400

Trp Gln 415

His Asn cctgagactc ccgccaggct attctacgca gctgtatctt agatgggagc a

120

180

240

300

351

- 587 044746 <400> 737

Glu Val Gln Leu 1

Val Glu Ser Gly 5

Gly Gly Leu Val 10

Gln Pro Gly Gly 15

Ser Leu Arg Leu 20

Ser Cys Ala Ala

Ser Gly Phe Thr 25

Val Ser Ser Asn

Tyr Met Asn Trp 35

Val Arg Gln Ala 40

Pro Gly Lys Gly

Leu Glu Trp Val 45

Ser Val Ile Tyr 50

Ser Gly Gly Ser 55

Thr Phe Tyr Ala 60

Asp Ser Val Arg

Gly Arg Phe Thr 65

Ile Ser Arg His 70

Asn Ser Lys Asn 75

Thr Leu Tyr Leu 80

Gln Met Asn Ser

Leu Arg Ala Glu 85

Asp Thr Ala Val 90

Tyr Tyr Cys Ala 95

Arg Asp Gly Ser

100

Ala Tyr Gly Met

Asp Val Trp Gly 105

Gln Gly Thr Thr 110

Val Thr Val Ser Ser

115 <210> 738 <211> 33 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>738 gcgagagatg ggagcgccta cggtatggac gtc <210>739 <211>11 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>739

Ala Arg Asp Gly Ser Ala Tyr Gly Met Asp Val

510 <210>740 <211>324

- 588 044746

DNA

Artificial

Synthetic

740 sequence <212>

<213>

<220>

<223>

<400>

gacatccaga atcacttgcc gggaaagccc aggttcagtg gaagattttg caagggacac tgacccagtc gggcaagtca ctaagctcct gcagtggatc caacttacta gactggagat tccatcctcc gagcattagt gatctatgct tgggacagat ctgtcaacag taaa ctgtctgcat agttttt taa gcatccagtt ttcactctca agttacagta ctgtaggaga attggtatca tgcaaagtgg ccatcagcag gtcctccgat cagagtcacc gcagaaacca ggtcccatca tctgcaacct caccttcggc

120

180

240

300

324 <210> 741 <211> 108 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 741

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 10 15

Asp Arg Val Thr Ile Thr Cys Arg 20

Ala Ser Gln Ser Ile Ser Ser Phe

thirty

Leu Asn Trp Tyr Gln Gln Lys Pro

40

Gly Lys Ala Pro Lys Leu Leu Ile 45

Tyr Ala Ala Ser Ser Leu Gln Ser

55

Gly Val Pro Ser Arg Phe Ser Gly 60

Ser Gly Ser Gly Thr Asp Phe Thr 65 70

Leu Thr Ile Ser Ser Leu Gln Pro

80

Glu Asp Phe Ala Thr Tyr Tyr Cys 85

Gln Gln Ser Tyr Ser Ser Pro Pro

95

Ile Thr Phe Gly Gln Gly Thr Arg

100

Leu Glu Ile Lys 105 <210> 742 <211> 18 <212> DNA <213> Artificial sequence

- 589 044746 <220>

<223> Synthetic <400>742 cagagcatta gtagtttt <210>743 <211>6 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>743

Gln Ser Ile Ser Ser Phe <210>744 <211>30 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>744 caacagagtt acagtagtcc tccgatcacc <210>745 <211>10 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>745

Gln Gln Ser Tyr Ser Ser Pro Pro Ile Thr

510 <210>746 <211>1344 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>746 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc60 tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgaactgggt ccgccaggct120 ccagggaagg ggctggagtg ggtctcag tt atttatagcg gtggtagcac attctacgca180 gactccgtga ggggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt240

- 590 044746

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatgggagc 300 gcctacggta tggacgtctg gggccaaggg accacggtca ccgtctcctc agcctccacc 360 aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc 600 aacgtgaatc acaagcccag caacaccaag gtggacaaga aagttgagcc caaatcttgt 660 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 720 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 780 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 840 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 900 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 960 tgcaaggtct ccaacaaagc cctcccagcc ccatcgaga aaaccatctc caaagccaaa 1020 gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 1080 aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1140 tggggagagca atggggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1200 gacggctcct tcttcctcta cagcaagctc accgtggac agagcaggtg gcagcagggg 1260 aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagtcc 1320 ctctccctgt ctccgggtaa atga 1344

<210> 747 <211> 447 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 747

Glu Val Gln 1

Ser Leu Arg

Tyr Met Asn 35

Ser Val Ile

Leu Val Glu Ser Gly 5

Leu Ser Cys Ala Ala 20

Trp Val Arg Gln Ala 40

Tyr Ser Gly Gly Ser

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Gly Phe Thr Val Ser Ser Asn 25 30

Pro Gly Lys Gly Leu Glu Trp Val 45

Thr Phe Tyr Ala Asp Ser Val Arg

- 591 044746

Gly Arg Phe Thr Ile 65

Ser Arg His Asn Ser 70

Lys Asn Thr Leu Tyr 75

Gln Met Asn Ser Leu

Arg Ala Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Asp Gly Ser Ala

100

Tyr Gly Met Asp Val

105

Trp Gly Gln Gly Thr

110

Val Thr Val Ser Ser

115

Ala Ser Thr Lys Gly 120

Pro Ser Val Phe Pro

125

Ala Pro Ser Ser Lys 130

Ser Thr Ser Gly Gly

135

Thr Ala Ala Leu Gly

140

Leu Val Lys Asp Tyr 145

Phe Pro Glu Pro Val 150

Thr Val Ser Trp Asn 155

Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe

170

Pro Ala Val Leu Gln

175

Ser Gly Leu Tyr Ser

180

Leu Ser Ser Val Val

185

Thr Val Pro Ser Ser

190

Leu Gly Thr Gln Thr 195

Tyr Ile Cys Asn Val 200

Asn His Lys Pro Ser 205

Thr Lys Val Asp Lys

210

Lys Val Glu Pro Lys

215

Ser Cys Asp Lys Thr

220

Thr Cys Pro Pro Cys 225

Pro Ala Pro Glu Leu 230

Leu Gly Gly Pro Ser 235

Phe Leu Phe Pro Pro

245

Lys Pro Lys Asp Thr

250

Leu Met Ile Ser Arg

255

Pro Glu Val Thr Cys

260

Val Val Val Asp Val

265

Ser His Glu Asp Pro

270

Val Lys Phe Asn Trp

275

Tyr Val Asp Gly Val

280

Glu Val His Asn Ala

285

Thr Lys Pro Arg Glu

290

Glu Gln Tyr Asn Ser

295

Thr Tyr Arg Val Val

300

Leu 80

Ala

Thr

Leu

Cys

Ser 160

Ser

Ser

Asn

His

Val 240

Thr

Glu

Lys

Ser

- 592 044746

Val

305

Leu

Thr

Val

Leu

His

310

Gln

Asp

Trp

Leu

Asn

315

Gly

Lys

Glu

Tyr

Lys 320

Cys

Lys

Val

Ser

Asn

325

Lys

Ala

Leu

Pro

Ala

330

Pro

Ile

Glu

Lys

Thr

335

Ile

Ser

Lys

Ala

Lys 340

Gly

Gln

Pro

Arg

Glu

345

Pro

Gln

Val

Tyr

Thr

350

Leu

Pro

Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

355 360

Ser Leu Thr Cys Leu

365

Val Lys Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

375 380

Gly Gln Pro Glu Asn Asn

385 390

Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

395 400

Asp Gly Ser Phe Phe Leu Tyr 405

Trp Gln Gln Gly Asn Val Phe 420

Ser Lys Leu Thr Val Asp Lys Ser Arg 410 415

Ser Cys Ser Val Met His Glu Ala Leu 425 430

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

435 440 445 <210> 748 <211> 648 <212> DNA <213> Artificial j subsequence <220> <223> Synthetic <400> 748 gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc atcacttgcc gggcaagtca gagcattagt agttttttaa attggtatca gcagaaacca gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca aggttcagtg gcagtggatc tggacagat ttcactctca ccatcagcag tctgcaacct gaagatttg caactacta ctgtcaacag agttacagta gtcctccgat caccttcggc caagggacac gactggagat taaacgaact gtggctgcac catctgtctt catcttcccg ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc tatccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg

120

180

240

300

360

420

480

540

- 593 044746 acgctgagca aagcagacta cgagaaacac ggcctgagct cgcccgtcac aaagagcttc aaagtctacg cctgcgaagt cacccatcag aacaggggag agtgttag

600

648 <210> 749 <211> 215 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 749

Asp Ile Gln Met Thr Gln Ser Pro 1 5

Ser Ser Leu Ser Ala Ser Val Gly

15

Asp Arg Val Thr Ile Thr Cys Arg 20

Ala Ser Gln Ser Ile Ser Ser Phe

thirty

Leu Asn Trp Tyr Gln Gln Lys Pro

40

Gly Lys Ala Pro Lys Leu Leu Ile 45

Tyr Ala Ala Ser Ser Leu Gln Ser

55

Gly Val Pro Ser Arg Phe Ser Gly 60

Ser Gly Ser Gly Thr Asp Phe Thr 65 70

Leu Thr Ile Ser Ser Leu Gln Pro

80

Glu Asp Phe Ala Thr Tyr Tyr Cys 85

Gln Gln Ser Tyr Ser Ser Pro Pro

95

Ile Thr Phe Gly Gln Gly Thr Arg

100

Leu Glu Ile Lys Arg Thr Val Ala

105 110

Ala Pro Ser Val Phe Ile Phe Pro

115 120

Pro Ser Asp Glu Gln Leu Lys Ser

125

Gly Thr Ala Ser Val Val Cys Leu

130 135

Leu Asn Asn Phe Tyr Pro Arg Glu

140

Ala Lys Val Gln Trp Lys Val Asp

145 150

Asn Ala Leu Gln Ser Gly Asn Ser

155 160

Gln Glu Ser Val Thr Glu Gln Asp

165

Ser Lys Asp Ser Thr Tyr Ser Leu

170 175

Ser Ser Thr Leu Thr Leu Ser Lys 180

Ala Asp Tyr Glu Lys His Lys Val

185 190

- 594 044746

Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser

Ser Pro Val Thr Lys

195 200205

Ser Phe Asn Arg Gly Glu Cys

210215 <210>750 <211>1332 <212>DNA <213>Artificial sequence <220>

<223> Synthetic <400>750 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc60 tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgaactgggt ccgccaggct120 ccagggaagg ggctggagtg ggtctca gtt atttatagcg gtggtagcac attctacgca180 gactccgtga ggggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatgggagc300 gcctacggta tggacgtctg gggccaaggg accacggtca ccgtctcctc agcctccacc360 aagggcccat cggtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctac acctgc600 aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt660 cccccatgcc caccgtgccc agcaccaggc ggtggcggac catcagtctt cctgttcccc720 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtgg tggtg780 gacgtgagcc aggaagaccc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg840 cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc900 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc960 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga1020 gagccacagg tgtacaccct gcccccatcc caggaggaga tgaccaagaa ccaggtcagc1080 ctgacctgcc tggtcaaagg ct tctacccc agcgacatcg ccgtggagtg ggagagcaat1140 gggcagccgg agaacaacta caagaccacg cctcccgtgc tggactccga cggctccttc1200 ttcctctaca gcaggctcac cgtggacaag agcaggtggc aggaggggaa tgtcttctca1260 tgctccgtga tg catgaggc tctgcacaac cactacacac agaagtccct ctccctgtct 1320 ctgggtaaat ga1332

- 595 044746 <210> 751 <211> 443 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 751

Glu Val Gln Leu Val

5

Glu Ser Gly Gly Gly

Leu Val Gln Pro Gly

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Phe Thr Val Ser Ser

Tyr Met Asn Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Ser Val Ile Tyr Ser 50

Gly Gly Ser Thr Phe 55

Tyr Ala Asp Ser Val 60

Gly Arg Phe Thr Ile 65

Ser Arg His Asn Ser 70

Lys Asn Thr Leu Tyr 75

Gln Met Asn Ser Leu

Arg Ala Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Asp Gly Ser Ala

100

Tyr Gly Met Asp Val

105

Trp Gly Gln Gly Thr

110

Val Thr Val Ser Ser

115

Ala Ser Thr Lys Gly 120

Pro Ser Val Phe Pro

125

Ala Pro Cys Ser Arg 130

Ser Thr Ser Glu Ser

135

Thr Ala Ala Leu Gly 140

Leu Val Lys Asp Tyr 145

Phe Pro Glu Pro Val 150

Thr Val Ser Trp Asn 155

Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe

170

Pro Ala Val Leu Gln

175

Ser Gly Leu Tyr Ser

180

Leu Ser Ser Val Val

185

Thr Val Pro Ser Ser

190

Leu Gly Thr Lys Thr

195

Tyr Thr Cys Asn Val

200

Asp His Lys Pro Ser 205

Gly

Asn

Val

Arg

Leu 80

Ala

Thr

Leu

Cys

Ser 160

Ser

Ser

Asn

- 596 044746

Thr Lys Val Asp Lys

210

Arg Val Glu Ser Lys

215

Tyr Gly Pro Pro Cys

220

Pro Cys Pro Ala Pro 225

Gly Gly Gly Gly Pro 230

Ser Val Phe Leu Phe 235

Pro Lys Pro Lys Asp

245

Thr Leu Met Ile Ser

250

Arg Thr Pro Glu Val

255

Cys Val Val Val Asp

260

Val Ser Gln Glu Asp

265

Pro Glu Val Gln Phe

270

Trp Tyr Val Asp Gly

275

Val Glu Val His Asn

280

Ala Lys Thr Lys Pro

285

Glu Glu Gln Phe Asn

290

Ser Thr Tyr Arg Val

295

Val Ser Val Leu Thr

300

Leu His Gln Asp Trp 305

Leu Asn Gly Lys Glu 310

Tyr Lys Cys Lys Val 315

Asn Lys Gly Leu Pro

325

Ser Ser Ile Glu Lys

330

Thr Ile Ser Lys Ala

335

Gly Gln Pro Arg Glu

340

Pro Gln Val Tyr Thr

345

Leu Pro Pro Ser Gln

350

Glu Met Thr Lys Asn

355

Gln Val Ser Leu Thr

360

Cys Leu Val Lys Gly

365

Tyr Pro Ser Asp Ile

370

Ala Val Glu Trp Glu

375

Ser Asn Gly Gln Pro

380

Asn Asn Tyr Lys Thr 385

Thr Pro Pro Val Leu 390

Asp Ser Asp Gly Ser 395

Phe Leu Tyr Ser Arg

405

Leu Thr Val Asp Lys

410

Ser Arg Trp Gln Glu

415

Asn Val Phe Ser Cys

420

Ser Val Met His Glu

425

Ala Leu His Asn His

430

Pro

Pro 240

Thr

Asn

Arg

Val

Ser 320

Lys

Glu

Phe

Glu

Phe 400

Gly

Tyr

Thr Gln Lys Ser Leu 435

Ser Leu Ser Leu Gly 440

Lys <210> 752 <211> 345 <212> DNA

- 597 044746 <213> Artificial sequence <220>

<223> Synthetic <400> 752 gaggtgcagc tcctgtgcag ccagggaagg gactccgtga caaatgaaca ggtatggacg tggtggagtc cctctgggtt ggctggagtg agggccgatt gcctgagagc tctggggcca tggaggaggc caccgtcagt ggtctcagtt caccatct cc tgaggacacg agggaccacg ttggtccagc agcaactaca atttatagcg agacacaatt gccgtgtatt gtcaccgtct ctggggggtc tgagctgggt gtggtagcac ccaagaacac actgtgcgag cctca cctgagactc ccgccaggct attctacgca gctgtatctt agaggctac

120

180

240

300

345 <210> 753 <211> 115 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>753

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

Arg Glu Gly Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr

100 105110

Val Ser Ser

115 <210>754 <211>27

- 598 044746 <212> DNA <213> Artificial sequence <220> <223> Synthetic <400>754 gcgagagagg gctacggtat ggacgtc27 <210>755 <211>9 <212> PROTEIN <213> Artificial sequence <220> <223> Synthetic <400>755

Ala Arg Glu Gly Tyr Gly Met Asp Val 15 <210>756 <211>1338 <212> DNA <213> Artificial sequence <220> <223> Synthetic

<400> 756 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt caccgtcagt agcaactaca tgagctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag aggggctac 300 ggtatggacg tctggggcca agggaccacg gtcaccgtct cctcagcctc caccaagggc 360 ccatcggtct tccccctggc accctcctcc aagagcacct ctggggggcac agcggccctg 420 ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 480 ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 540 agcagcgtgg tgaccgtgcc ctccagcagc ttggggcaccc agacctacat ctgcaacgtg 600 aatcacaagc ccagcaacac caaggtggac aagaaagttg agcccaaatc ttgtgacaaa 660 actcacacat gccaccgtg cccagcacct gaactcctgg ggggaccgtc agtcttcctc 720 ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 780 gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 840 gaggtgcata atgccaagac aaagccgcgg gagggagt acaacagcac gtaccgtgtg 900

- 599 044746 gtcagcgtcc gtctccaaca ccccgagaac gtcagcctga agcaatgggc tccttcttcc ttctcatgct ctgtctccgg tcaccgtcct aagccctccc cacaggtgta cctgcctggt agccggagaa tctacagcaa ccgtgatgca gtaaatga gcaccaggac agcccccatc caccctgccc caaaggcttc caactacaag gctcaccgtg tgaggctctg tggctgaatg gagaaaacca ccatcccggg tatcccagcg accacgcctc gacaagagca cacaaccact gcaaggagta tctccaaagc atgagctgac acatcgccgt ccgtgctgga ggtggcagca acacgc agaa caagtgcaag caaagggcag caagaaccag ggagtgggag ctccgacggc ggggaacgtc gtccctctcc

960

1020

1080

1140

1200

1260

1320

1338 <210> 757 <211> 445 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 757

Glu Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly 10

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Tyr Met

Ser Trp 35

Val Arg

Gln Ala

Pro Gly

Ser Val

Ile Tyr

Ser Gly

Gly Ser 55

Thr Phe

Gly Arg 65

Phe Thr

Ile Ser

Arg His

Asn Ser

Gln Met

Asn Ser

Leu Arg 85

Ala Glu

Asp Thr

Arg Glu

Gly Tyr

100

Gly Met

Asp Val

Trp Gly 105

Val Ser

Ser Ala 115

Ser Thr

Lys Gly

120

Pro Ser

Ser Ser

130

Lys Ser

Thr Ser

Gly Gly 135

Thr Ala

Leu Val

Phe Thr

Lys Gly

Tyr Ala 60

Lys Asn 75

Ala Val

Gln Gly

Val Phe

Ala Leu 140

Glin Pro

Val Ser

Leu Glu 45

Asp Ser

Gly Gly 15

Ser Asn

Trp Val

Val Lys

Thr Leu

Tyr Tyr

Thr Thr

110

Pro Leu 125

Gly Cys

Tyr Leu 80

Cys Ala 95

Val Thr

Ala Pro

Leu Val

- 600 044746

Lys 145

Leu

Leu

Thr

Val

Pro 225

Phe

Val

Phe

Pro

Thr 305

Val

Ala

Arg

Gly

Pro 385

Asp Tyr Phe

Thr Ser Gly

Tyr Ser Leu

180

Gln Thr Tyr

195

Asp Lys Lys 210

Pro Cys Pro

Pro Pro Lys

Thr Cys Val

260

Asn Trp Tyr

275

Arg Glu Glu 290

Val Leu His

Ser Asn Lys

Lys Gly Gln

340

Asp Glu Leu

355

Phe Tyr Pro 370

Glu Asn Asn

Pro Glu Pro

150

Val His Thr 165

Ser Ser Val

Ile Cys Asn

Val Glu Pro

215

Ala Pro Glu

230

Pro Lys Asp 245

Val Val Asp

Val Asp Gly

Gln Tyr Asn

295

Gln Asp Trp

310

Ala Leu Pro 325

Pro Arg Glu

Thr Lys Asn

Ser Asp Ile

375

Tyr Lys Thr

390

Val Thr Val

Phe Pro Ala

170

Val Thr Val

185

Val Asn His 200

Lys Ser Cys

Leu Leu Gly

Thr Leu Met

250

Val Ser His

265

Val Glu Val 280

Ser Thr Tyr

Leu Asn Gly

Ala Pro Ile

330

Pro Gln Val

345

Gln Val Ser 360

Ala Val Glu

Thr Pro Pro

Ser Trp Asn 155

Val Leu Gln

Pro Ser Ser

Lys Pro Ser

205

Asp Lys Thr 220

Gly Pro Ser 235

Ile Ser Arg

Glu Asp Pro

His Asn Ala

285

Arg Val Val

300

Lys Glu Tyr 315

Glu Lys Thr

Tyr Thr Leu

Leu Thr Cys

365

Trp Glu Ser

380

Val Leu Asp 395

Ser Gly Ala

160

Ser Ser Gly

175

Ser Leu Gly 190

Asn Thr Lys

His Thr Cys

Val Phe Leu

240

Thr Pro Glu

255

Glu Val Lys 270

Lys Thr Lys

Ser Val Leu

Lys Cys Lys

320

Ile Ser Lys

335

Pro Pro Ser 350

Leu Val Lys

Asn Gly Gln

Ser Asp Gly

400

- 601 044746

Ser Phe Phe Leu

Tyr Ser Lys Leu 405

Thr Val Asp Lys 410

Ser Arg Trp Gln

415

Gln Gly Asn Val

420

Phe Ser Cys Ser

Val Met His Glu 425

Ala Leu His Asn

430

His Tyr Thr Gln

435

Lys Ser Leu Ser

440

Leu Ser Pro Gly

Lys

445

<210> 758 <211> 1326 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 758 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc tcctgtgcag cctctggggtt caccgtcagt agcaactaca tgagctggggt ccgccaggct ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag aggggctac ggtatggacg tctggggcca agggaccacg gtcaccgtct cctcagcctc caccaagggc ccatcggtct tccccctggc gccctgctcc aggagcacct ccgagagcac agccgccctg ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc agcagcgtgg tgaccgtgcc ctccagcagc ttggggcacga agacctacac ctgcaacgta gatcacaagc ccagcaacac caaggtggac aagagagttg agtccaaata tggtccccca tgccaccgt gccagcacc aggcggtggc ggaccatcag tcttcctgtt ccccccaaaa cccaaggaca ctctcatgat ctcccggacc cctgaggtca cgtgcgtggt ggtggacgtg agccaggaag accccgaggt ccagttcaac tggtacgtgg atggcgtgga ggtgcataat gccaagacaa agccgcggga ggagcagttc aacagcacgt accgtgtggt cagcgtcctc accgtcctgc accaggactg gctgaacggc aaggagtaca agtgcaaggt ctccaacaaa ggcctcccgt cctccatcga gaaaaccatc tccaaagcca aagggcagcc ccgagagcca caggtgtaca ccctgccccc atcccaggag gagatgacca agaaccaggt cagcctgacc tgcctggtca aaggcttcta ccccagcgac atcgccgtgg agggggagag caatggggcag ccggagaaca actacaagac cacgcctccc gtgctggact ccgacggctc cttcttcctc tacagcaggc tcaccgtgga caagagcagg tggcaggagg ggaatgtctt ctcatgctcc

120

180

240

300

360

420

480

540

600

660

720

780

840

900

960

1020

1080

1140

1200

1260

- 602 044746 gtgatgcatg aggctctgca caaccactac acacagaagt ccctctccct gtctctgggt

1320

1326 aaatga <210> 759 <211> 441 <212> PROTEIN <213> Artificial sequence <220>

< 223 > Synthetic < 400 > 759

Glu Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Leu Val Gln Pro Gly Gly

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Val Ser Ser Asn 25 30

Tyr Met Ser Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ser Val Ile Tyr Ser Gly Gly Ser

55

Thr Phe Tyr Ala Asp Ser Val Lys 60

Gly Arg Phe Thr Ile Ser Arg His 65 70

Asn Ser Lys Asn Thr Leu Tyr Leu

80

Gln Met Asn Ser Leu Arg Ala Glu 85

Asp Thr Ala Val Tyr Tyr Cys Ala

95

Arg Glu Gly Tyr Gly Met Asp Val

100

Trp Gly Gln Gly Thr Thr Val Thr

105 110

Val Ser Ser Ala Ser Thr Lys Gly

115 120

Pro Ser Val Phe Pro Leu Ala Pro

125

Cys Ser Arg Ser Thr Ser Glu Ser

130 135

Thr Ala Ala Leu Gly Cys Leu Val

140

Lys Asp Tyr Phe Pro Glu Pro Val

145 150

Thr Val Ser Trp Asn Ser Gly Ala

155 160

Leu Thr Ser Gly Val His Thr Phe

165

Pro Ala Val Leu Gln Ser Ser Gly

170 175

Leu Tyr Ser Leu Ser Ser Val Val 180

Thr Val Pro Ser Ser Ser Leu Gly

185 190

- 603 044746

Thr Lys Thr Tyr Thr 195

Cys Asn Val Asp His

200

Lys Pro Ser Asn Thr

205

Val Asp Lys Arg Val

210

Glu Ser Lys Tyr Gly

215

Pro Pro Cys Pro Pro

220

Pro Ala Pro Gly Gly 225

Gly Gly Pro Ser Val 230

Phe Leu Phe Pro Pro 235

Pro Lys Asp Thr Leu

245

Met Ile Ser Arg Thr

250

Pro Glu Val Thr Cys

255

Val Val Asp Val Ser

260

Gln Glu Asp Pro Glu

265

Val Gln Phe Asn Trp

270

Val Asp Gly Val Glu

275

Val His Asn Ala Lys

280

Thr Lys Pro Arg Glu

285

Gln Phe Asn Ser Thr

290

Tyr Arg Val Val Ser

295

Val Leu Thr Val Leu

300

Gln Asp Trp Leu Asn 305

Gly Lys Glu Tyr Lys 310

Cys Lys Val Ser Asn 315

Gly Leu Pro Ser Ser

325

Ile Glu Lys Thr Ile

330

Ser Lys Ala Lys Gly

335

Pro Arg Glu Pro Gln

340

Val Tyr Thr Leu Pro

345

Pro Ser Gln Glu Glu

350

Thr Lys Asn Gln Val

355

Ser Leu Thr Cys Leu 360

Val Lys Gly Phe Tyr

365

Ser Asp Ile Ala Val

370

Glu Trp Glu Ser Asn

375

Gly Gln Pro Glu Asn 380

Tyr Lys Thr Thr Pro 385

Pro Val Leu Asp Ser 390

Asp Gly Ser Phe Phe 395

Tyr Ser Arg Leu Thr

405

Val Asp Lys Ser Arg

410

Trp Gln Glu Gly Asn

415

Phe Ser Cys Ser Val

420

Met His Glu Ala Leu

425

His Asn His Tyr Thr

430

Lys

Cys

Lys 240

Val

Tyr

Glu

His

Lys 320

Gln

Met

Pro

Asn

Leu 400

Val

Gln

Lys Ser Leu Ser Leu

435

Ser Leu Gly Lys

440

- 604 044746 <210> 760 <211> 351 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 760

gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt aatagtcagt cgcaactaca tgatctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagggc tgaggacacg gccgtatatt actgtgcgag agatctggggt 300 acaggaggta tggacgtctg gggccaaggg accacggtca ccgtctcctc a 351

<210> 761 <211> 1344 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 761 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt aatagtcagt cgcaactaca tgatctggggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgagggc tgaggacacg gccgtatatt actgtgcgag agatctggggt 300 acaggaggta tggacgtctg gggccaaggg accacggtca ccgtctcctc agcctccacc 360 aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc 600 aacgtgaatc acaagcccag caacaccaag gtggacaaga aagttgagcc caaatcttgt 660 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 720 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 780 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 840 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 900

- 605 044746 cgtgtggtca tgcaaggtct gggcagcccc aaccaggtca tggggagagca gacggctcct aacgtcttct ctctccctgt gcgtcctcac ccaacaaagc gagaaccaca gcctgacctg atgggcagcc tcttcctcta catgctccgt ctccgggtaa cgtcc tgcac cctcccagcc ggtgtacacc cctggtcaaa ggagaacaac cagcaagctc gatgcatgag atga caggactggc cccatcgaga ctgcccccat ggcttctatc tacaagacca accgtggaca gctctgcaca tgaatggcaa aaaccatctc cccgggatga ccagcgacat cgcctcccgt agagcagg tg accactacac ggagtacaag caaagccaaa gctgaccaag cgccgtggag gctggactcc gcagcagggg gcagaagtcc

960

1020

1080

1140

1200

1260

1320

1344 <210> 762 <211> 447 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 762

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly 1 5 10 15

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Tyr Met

Ile Trp 35

Val Arg

Gln Ala

Ser Val

Ile Tyr

Ser Gly

Gly Ser 55

Gly Arg 65

Phe Thr

Ile Ser

Arg His

Gln Met

Asn Ser

Leu Arg 85

Ala Glu

Arg Asp

Leu Gly

100

Thr Gly

Gly Met

Val Thr

Val Ser

115

Ser Ala

Ser Thr

120

Ala Pro

130

Ser Ser

Lys Ser

Thr Ser 135

Ser Gly 25

Pro Gly

Thr Phe

Asn Ser

Asp Thr 90

Asp Val 105

Lys Gly

Gly Gly

Leu Ile

Lys Gly

Tyr Ala 60

Lys Asn 75

Ala Val

Trp Gly

Pro Ser

Thr Ala

140

Val Ser

Leu Glu 45

Asp Ser

Thr Leu

Tyr Tyr

Gln Gly

110

Val Phe 125

Ala Leu

Arg Asn

Trp Val

Val Lys

Tyr Leu 80

Cys Ala 95

Thr Thr

ProLeu

Gly Cys

- 606 044746

Leu 145

Gly

Ser

Leu

Thr

Thr 225

Phe

Pro

Val

Thr

Val 305

Cys

Ser

Pro

Val

Gly 385

Val Lys Asp

Ala Leu Thr

Gly Leu Tyr

180

Gly Thr Gln

195

Lys Val Asp 210

Cys Pro Pro

Leu Phe Pro

Glu Val Thr

260

Lys Phe Asn

275

Lys Pro Arg 290

Leu Thr Val

Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn

150 155

Ser Gly Val His Thr Phe Pro Ala Val Leu Gln

165 170 175

Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser

185 190

Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser

200 205

Lys Lys Val Glu Pro Lys Ser Cys Asp Lys Thr

215 220

Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

230 235

Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

245 250 255

Cys Val Val Val Asp Val Ser His Glu Asp Pro

265 270

Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

280 285

Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

295 300

Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

310 315

Lys Val Ser Asn 325 Lys Ala Leu Pro Ala 330 Pro Ile Lys Ala Lys 340 Gly Gln Pro Arg Glu 345 Pro Gln Val Ser Arg 355 Asp Glu Leu Thr Lys 360 Asn Gln Val Ser

Glu Lys Thr

335

Tyr Thr Leu

350

Leu Thr Cys 365

Lys Gly Phe Tyr Pro Ser Asp

370 375

Ile Ala Val Glu Trp Glu Ser

380

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

390 395

Ser 160

Ser

Ser

Asn

His

Val 240

Thr

Glu

Lys

Ser

Lys 320

Ile

Pro

Leu

Asn

Ser

400

- 607 044746

Asp Gly Ser Phe

Phe Leu Tyr Ser 405

Lys Leu Thr Val

410

Asp Lys Ser Arg

415

Trp Gln Gln Gly

420

Asn Val Phe Ser

Cys Ser Val Met 425

His Glu Ala Leu

430

His Asn His Tyr

435

Thr Gln Lys Ser

440

Leu Ser Leu Ser

Pro Gly Lys 445 <210>

<211>

<212>

<213>

763

360

DNA

Artificial sequence <220>

<223> Синтетическая <400> 763 caggtgcagc tcctgtgtag ccaggcaagg gcagactccg ctgcaaatga gaggcagctg tggtggagtc cctctggatt ggctggagtg tgaagggccg acagcctgag cggatgcttt tgggggaggc caccttcagt ggtggcagtt attcaccatc acctgaggac tgatatctgg gtggtccagc atttatggca atatcatatg tccagagaca acggctgtgt ggccaaggga ctgggaggtc tggactgggt atggaagtaa attccaagaa attactgtgc caatggtcac cctgagactc ccgccaggct taaatactat cacgctgtat gaaagatagg cgtctcttca

120

180

240

300

360 <210> 764 <211> 120 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 764

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Val Ala 20

Ser Gly Phe Thr Phe Ser Ile Tyr 25 30

Gly Met Asp Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ala Val Ile Ser Tyr Asp Gly Ser

55

Asn Lys Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ser Lys Asn Thr Leu Tyr

80

- 608 044746

Leu Gln Met Asn

Ser Leu Arg Pro Glu Asp Thr

90

Ala Val Tyr Tyr Cys 95

Ala Lys Asp Arg Glu Ala Ala Ala Asp Ala Phe Asp

100 105

Ile Trp Gly Gln

110

Gly Thr Met Val Thr Val Ser Ser

115 120 <210> 765 <211> 24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>765 ggattcacct tcagtattta tggc <210>766 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 766

Gly Phe Thr Phe Ser Ile Tyr Gly

5 <210> 767 <211> 39 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>767 gcgaaagata gggaggcagc tgcggatgct tttgatatc <210>768 <211>13 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 768

Ala Lys Asp Arg Glu Ala Ala Ala Asp Ala Phe Asp Ile

- 609 044746 <210> 769 <211> 321 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 769

gacatccaga tgaccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60 atcacttgtc gggcgagtca gggtattagc agctggttag cctggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcacagtgg ggtcccatca 180 aggttcagcg gcagtggatc tggacagat ttcactctca ccatcagcag cctgcagcct 240 gaagatttg caactacta ttgtcaacag gctaacagtt tccgtctcac tttcggcgga 300 gggaccaagg tggagatcaa a 321

<210> 770 <211> 107 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>770

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

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Trp 20 2530

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Ser Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Phe Arg Leu 85 9095

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100105

- 610 044746 <210> 771 <211> 27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>771 caacaggcta acagtttccg tctcact27 <210>772 <211>9 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>772

Gln Gln Ala Asn Ser Phe Arg Leu Thr 15 <210>773 <211>1353 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 773 caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgtgtag cctctggatt caccttcagt atttatggca tggactgggt ccgccaggct 120 ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactat 180 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag acctgaggac acggctgtgt attackgtgc gaaagatagg 300 gaggcagctg cggatgcttt tgatatctgg ggccaaggga caatggtcac cgtctcttca 360 gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg 420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga 720 ccgtcagtct tcctcttccc cccaaaaccc aaggacacc tcatgatctc ccggacccct 780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 840

- 611 044746

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcggggaga gcagtacaac 900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 960 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1020 aaagccaaag ggcagccccg agaaccacag gtgtacacc tgcccccatc ccgggatgag 1080 ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc 1140 gccgtggagt ggggagagcaa tggggcagccg gagaacaact acaagaccac gcctcccgtg 1200 ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg 1260 cagcagggga acgtcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg 1320 cagaagtccc tctccctgtc tccggggtaaa tga 1353

<210> 774 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 774

Gln Val Gln 1

Leu Val Glu Ser Gly Gly 5

Gly Val Val Gln Pro 10

Gly Arg 15

Ser Leu Arg

Leu Ser Cys Val Ala Ser

25

Gly Phe Thr Phe Ser

Ile Tyr

Gly Met Asp

Trp Val Arg Gln Ala Pro

Gly Lys Gly Leu Glu 45

Trp Val

Ala Val Ile

Ser Tyr Asp Gly Ser Asn Lys 55

Tyr Tyr Ala Asp Ser Val 60

Lys 65

Leu

Ala

Gly

Gly Arg Phe

Gln Met Asn

Lys Asp Arg

100

Thr Met Val

115

Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr

75

Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr 85 90

Glu Ala Ala Ala Asp Ala Phe Asp Ile Trp

105 110

Thr Val Ser Ser Ala Ser Thr Lys Gly Pro

120 125

Leu Tyr 80

Tyr Cys 95

Gly Gln

Ser Val

Phe Pro Leu Ala Pro Ser Ser Lys

130 135

Ser Thr Ser Gly Gly Thr Ala Ala

140

- 612 044746

Leu Gly Cys Leu Val 145

Lys Asp Tyr Phe Pro 150

Glu Pro Val Thr Val 155

Trp Asn Ser Gly Ala

165

Leu Thr Ser Gly Val

170

His Thr Phe Pro Ala

175

Leu Gln Ser Ser Gly

180

Leu Tyr Ser Leu Ser

185

Ser Val Val Thr Val

190

Ser Ser Ser Leu Gly 195

Thr Gln Thr Tyr Ile 200

Cys Asn Val Asn His

205

Pro Ser Asn Thr Lys 210

Val Asp Lys Lys Val

215

Glu Pro Lys Ser Cys

220

Lys Thr His Thr Cys 225

Pro Pro Cys Pro Ala 230

Pro Glu Leu Leu Gly 235

Pro Ser Val Phe Leu

245

Phe Pro Pro Lys Pro

250

Lys Asp Thr Leu Met

255

Ser Arg Thr Pro Glu

260

Val Thr Cys Val Val

265

Val Asp Val Ser His

270

Asp Pro Glu Val Lys

275

Phe Asn Trp Tyr Val

280

Asp Gly Val Glu Val

285

Asn Ala Lys Thr Lys 290

Pro Arg Glu Glu Gln

295

Tyr Asn Ser Thr Tyr 300

Val Val Ser Val Leu 305

Thr Val Leu His Gln 310

Asp Trp Leu Asn Gly 315

Glu Tyr Lys Cys Lys

325

Val Ser Asn Lys Ala

330

Leu Pro Ala Pro Ile

335

Lys Thr Ile Ser Lys

340

Ala Lys Gly Gln Pro

345

Arg Glu Pro Gln Val

350

Thr Leu Pro Pro Ser

355

Arg Asp Glu Leu Thr 360

Lys Asn Gln Val Ser

365

Thr Cys Leu Val Lys

370

Gly Phe Tyr Pro Ser

375

Asp Ile Ala Val Glu

380

Glu Ser Asn Gly Gln

Pro Glu Asn Asn Tyr

Lys Thr Thr Pro Pro

Ser 160

Val

Pro

Lys

Asp

Gly 240

Ile

Glu

His

Arg

Lys 320

Glu

Tyr

Leu

Trp

Val

- 613 044746

385 390 395 400

Leu Asp Ser Asp Gly Ser 405

Lys Ser Arg Trp Gln Gln 420

Glu Ala Leu His Asn His 435

Phe Phe Leu Tyr

410

Gly Asn Val Phe

425

Tyr Thr Gln Lys

440

Ser Lys Leu Thr Val Asp

415

Ser Cys Ser Val Met His

430

Ser Leu Ser Leu Ser Pro

445

Gly Lys

450 <210> 775 <211> 645 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 775 gacatccaga tgaccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60 atcacttgtc gggcgagtca gggtattagc agctggttag cctggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcacagtgg ggtcccatca 180 aggttcagcg gcagtggatc tggacagat ttcactctca ccatcagcag cctgcagcct 240 gaagatttg caactacta ttgtcaacag gctaacagtt tccgtctcac tttcggcgga 300 gggaccaagg tggagatcaa acgaactgtg gctgcaccat ctgtcttcat cttcccgcca 360 tctgatgagc agttgaaatc tggaactgcc tctgttgtgt gcctgctgaa taacttctat 420 cccagagagg ccaaagtaca gtggaaggtg gataacgccc tccaatcggg taactcccag 480 gagagtgtca cagagcagga cagcaaggac agcacctaca gcctcagcag caccctgacg 540 ctgagcaaag cagactacga gaaacacaaa gtctacgcct gcgaagtcac ccatcaggggc 600 ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gttag 645

<210> 776 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 776

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

5 10 15

- 614 044746

Asp Arg Val

Thr Ile Thr 20

Cys Arg Ala

Leu Ala Trp

Tyr Gln Gln

Lys Pro Gly 40

Tyr Ala Ala 50

Ser Ser Leu

His Ser Gly 55

Ser Gly Ser 65

Gly Thr Asp

Phe Thr Leu

Glu Asp Phe

Ala Thr Tyr 85

Tyr Cys Gln

Thr Phe Gly

Gly Gly Thr 100

Lys Val Glu

105

Ser Gln Gly

Lys Ala Pro

Val Pro Ser 60

Thr Ile Ser 75

Gln Ala Asn 90

Ile Lys Arg

Ile Ser Ser

Lys Leu Leu 45

Arg Phe Ser

Ser Leu Gln

Ser Phe Arg

Thr Val Ala

110

Pro Ser Val

115

Phe Ile Phe

Pro Pro Ser

120

Asp Glu Gln

Leu Lys Ser 125

Thr Ala Ser

130

Val Val Cys

Leu Leu Asn 135

Lys Val Gln 145

Trp Lys Val

150

Asp Asn Ala

Asn Phe Tyr 140

Leu Gln Ser 155

Pro Arg Glu

Gly Asn Ser

Glu Ser Val

Thr Glu Gln

165

Asp Ser Lys

Asp Ser Thr 170

Tyr Ser Leu

175

Ser Thr Leu

Thr Leu Ser 180

Lys Ala Asp

185

Tyr Glu Lys

His Lys Val

190

Ala Cys Glu

195

Val Thr His

Gln Gly Leu

200

Ser Ser Pro

Val Thr Lys 205

Trp

Ile

Gly

Pro 80

Leu

Ala

Gly

Ala

Gln 160

Ser

Tyr

Ser

Phe Asn Arg

210

Gly Glu Cys <210> 777 <211> 1341 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 777

- 615 044746

caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgtgtag cctctggatt caccttcagt atttatggca tggactgggt ccgccaggct 120 ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactat 180 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagcctgag acctgaggac acggctgtgt attackgtgc gaaagatagg 300 gaggcagctg cggatgcttt tgatatctgg ggccaaggga caatggtcac cgtctcttca 360 gcctccacca agggcccatc ggtcttcccc ctggcgccct gctccaggag cacctccgag 420 agcacagccg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg 480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540 ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacgaagacc 600 tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 660 aaatatggtc ccccatgccc accgtgccca gcaccaggcg gtggcggacc atcagtcttc 720 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 780 gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 840 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cagtaccgt 900 gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 960 aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1020 cagccccgag agccacaggt gtacaccctg ccccatccc aggaggat gaccaagaac 1080 caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1140 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1200 ggctccttct tcctctacag caggctcacc gtggacaaga gcaggtggca ggaggggaat 1260 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagtccctc 1320 tccctgtctc tgggtaaatg a 1341

<210> 778 <211> 446 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>778

Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg

5 1015

Ser Leu Arg Leu Ser Cys Val Ala Ser 2025

Gly Phe Thr Phe Ser Ile Tyr

- 616 044746

Gly

Ala

Lys 65

Leu

Ala

Gly

Phe

Leu 145

Trp

Leu

Ser

Pro

Pro 225

Leu

Glu

Gln

Met Asp Trp Val Arg 35

Val Ile Ser Tyr Asp 50

Gly Arg Phe Thr Ile 70

Gln Met Asn Ser Leu

Lys Asp Arg Glu Ala

100

Thr Met Val Thr Val

115

Pro Leu Ala Pro Cys 130

Gly Cys Leu Val Lys

150

Asn Ser Gly Ala Leu

165

Gln Ser Ser Gly Leu 180

Ser Ser Leu Gly Thr

195

Ser Asn Thr Lys Val 210

Cys Pro Pro Cys Pro

230

Phe Pro Pro Lys Pro

245

Val Thr Cys Val Val

260

Phe Asn Trp Tyr Val

Gln Ala Pro Gly Lys 40

Gly Ser Asn Lys Tyr 55

Ser Arg Asp Asn Ser 75

Arg Pro Glu Asp Thr

Ala Ala Asp Ala Phe 105

Ser Ser Ala Ser Thr

120

Ser Arg Ser Thr Ser 135

Asp Tyr Phe Pro Glu

155

Thr Ser Gly Val His

170

Tyr Ser Leu Ser Ser 185

Lys Thr Tyr Thr Cys

200

Asp Lys Arg Val Glu 215

Ala Pro Gly Gly Gly

235

Lys Asp Thr Leu Met

250

Val Asp Val Ser Gln

265

Asp Gly Val Glu Val

Gly Leu Glu Trp Val 45

Tyr Ala Asp Ser Val 60

Lys Asn Thr Leu Tyr 80

Ala Val Tyr Tyr Cys 95

Asp Ile Trp Gly Gln 110

Lys Gly Pro Ser Val

125

Glu Ser Thr Ala Ala 140

Pro Val Thr Val Ser

160

Thr Phe Pro Ala Val

175

Val Val Thr Val Pro

190

Asn Val Asp His Lys 205

Ser Lys Tyr Gly Pro 220

Gly Pro Ser Val Phe

240

Ile Ser Arg Thr Pro

255

Glu Asp Pro Glu Val

270

His Asn Ala Lys Thr

- 617 044746

275

280

285

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

290 295300

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

305 310 315320

Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser

325 330335

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

340 345350

Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

355 360365

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

370 375380

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

385 390 395400

Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp

405 410415

Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

420 425430

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435 440445 <210>779 <211>348 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

<400> 779 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt cattgtcagt aggaactaca tgagctggggt ccgccaggct 120 ccagggaagg gactggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgctt caccattctcc cgacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgaaagc tgaggacacg gccgtgtatt actgtgcgag agagctacga 300 gggtactttg actactgggg ccagggaacc ctggtcaccg tctcctca 348

- 618 044746 <210> 780 <211> 116 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>780

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ile Val Ser Arg Asn 20 2530

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Ser Leu Lys Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

Arg Glu Leu Arg Gly Tyr Phe Asp Tyr Trp Gly Gln Gly Thr Leu Val

100 105110

Thr Val Ser Ser

115 <210>781 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>781 gggttcattg tcagtaggaa ctac <210>782 <211>8 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic

- 619 044746 <400>782

Gly Phe Ile Val Ser Arg Asn Tyr <210>783 <211>30 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>783 gcgagagagc tacgagggta ctttgactac30 <210>784 <211>10 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>784

Ala Arg Glu Leu Arg Gly Tyr Phe Asp Tyr

510 < 210> 785 < 211> 321 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>785 gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc60 atcacttgct gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca120 gggaaagccc ctaagctcct gatctatgct gcatccactt tg caaagtgg ggtcccatca180 aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct240 gaagattttg caacttatta ctgtcaactg cttaatagtt acccgtacac ttttggccag300 gggaccaagc tggagatcaa a321 <210>

<211>

<212>

<213>

786

107

PROTEIN

Artificial sequence

Synthetic <220>

<223>

- 620 044746 <400>786

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

5 1015

Asp Arg Val Thr Ile Thr Cys Trp Ala Ser Gln Gly Ile Ser Ser Tyr 20 2530

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Leu Leu Asn Ser Tyr Pro Tyr 85 9095

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100105 <210>787 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>787 caactgctta atagttaccc gtacact <210>788 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>788

Gln Leu Leu Asn Ser Tyr Pro Tyr Thr <210>789 <211>1341 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

- 621 044746

<400> 789 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt cattgtcagt aggaactaca tgagctggggt ccgccaggct 120 ccagggaagg gactggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgctt caccattctcc cgacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgaaagc tgaggacacg gccgtgtatt actgtgcgag agagctacga 300 gggtactttg actactgggg ccagggaacc ctggtcaccg tctcctcagc ctccaccaag 360 ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctgggggg cacagcggcc 420 ctggggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 480 gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 540 ctcagcagcg tggtgaccgt gccctccagc agcttggggca cccagaccta catctgcaac 600 gtgaatcaca agccagcaa caccaaggtg gacaagaaag ttgagcccaa atcttgtgac 660 aaaactcaca catgcccacc gtgccagca cctgaactcc tggggggacc gtcagtcttc 720 ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc 780 gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc 840 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cagtaccgt 900 gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc 960 aaggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg 1020 cagccccgag aaccacaggt gtacaccctg ccccatccc gggatgagct gaccaagaac 1080 caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg 1140 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1200 ggctccttct tcctctacag caagctcacc gtggacaaga gcaggtggca gcaggggaac 1260 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagtccctc 1320 tccctgtctc cggggtaaatg a 1341

<210> 790 <211> 446 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 790

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

- 622 044746

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Phe Ile Val Ser Arg 30

Tyr Met Ser Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Ser Val Ile Tyr Ser 50

Gly Gly Ser Thr Phe 55

Tyr Ala Asp Ser Val 60

Gly Arg Phe Thr Ile 65

Ser Arg His Asn Ser 70

Lys Asn Thr Leu Tyr 75

Gln Met Asn Ser Leu

Lys Ala Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Glu Leu Arg Gly

100

Tyr Phe Asp Tyr Trp

105

Gly Gln Gly Thr Leu

110

Thr Val Ser Ser Ala

115

Ser Thr Lys Gly Pro

120

Ser Val Phe Pro Leu

125

Pro Ser Ser Lys Ser 130

Thr Ser Gly Gly Thr

135

Ala Ala Leu Gly Cys 140

Val Lys Asp Tyr Phe 145

Pro Glu Pro Val Thr 150

Val Ser Trp Asn Ser 155

Ala Leu Thr Ser Gly

165

Val His Thr Phe Pro

170

Ala Val Leu Gln Ser

175

Gly Leu Tyr Ser Leu

180

Ser Ser Val Val Thr

185

Val Pro Ser Ser Ser

190

Gly Thr Gln Thr Tyr

195

Ile Cys Asn Val Asn

200

His Lys Pro Ser Asn

205

Lys Val Asp Lys Lys

210

Val Glu Pro Lys Ser

215

Cys Asp Lys Thr His

220

Cys Pro Pro Cys Pro 225

Ala Pro Glu Leu Leu 230

Gly Gly Pro Ser Val 235

Leu Phe Pro Pro Lys

245

Pro Lys Asp Thr Leu

250

Met Ile Ser Arg Thr

255

Glu Val Thr Cys Val

260

Val Val Asp Val Ser

265

His Glu Asp Pro Glu

270

Asn

Val

Lys

Leu 80

Ala

Val

Ala

Leu

Gly 160

Ser

Leu

Thr

Thr

Phe 240

Pro

Val

- 623 044746

Lys Phe

Lys Pro

290

Leu Thr 305

Lys Val

Asn Trp 275

Arg Glu

Val Leu

Ser Asn

Tyr Val

Glu Gln

His Gln

310

Lys Ala 325

Lys Ala

Lys Gly

340

Glin Pro

Ser Arg

Asp Glu 355

Leu Thr

Lys Gly

370

Phe Tyr

Pro Ser

Asp Gly

280

Tyr Asn 295

Asp Trp

Leu Pro

Arg Glu

Lys Asn

360

Asp Ile 375

Val Glu

Ser Thr

Leu Asn

Ala Pro

330

Pro Gln 345

Gln Val

Ala Val

Val His

Tyr Arg

300

Gly Lys 315

Ile Glu

Val Tyr

Ser Leu

Glu Trp

380

Gln Pro 385

Glu Asn

Asn Tyr

390

Lys Thr

Thr Pro

Pro Val 395

Gly Ser

Phe Phe

Leu Tyr 405

Ser Lys

Leu Thr

410

Val Asp

Gln Gln

Gly Asn

420

Val Phe

Ser Cys

Ser Val

425

Met His

Asn His

Tyr Thr 435

Gln Lys

Ser Leu

440

Ser Leu

Ser Pro <210> 791 <211> 645 <212> DNA <213> Artificial sequence

Synthetic

791 <220>

<223>

<400>

gacatccagt atcacttgct gggaaagccc aggttcagcg gaagattttg tgacccagtc gggccagtca ctaagctcct gcagtggatc caacttatta tccatccttc gggcattagc gatctatgct tgggacagaa ctgtcaactg ctgtctgcat agttatttag gcatccactt ttcactctca ct taatagtt

Asn Ala 285

Val Val

Glu Tyr

Lys Thr

Thr Leu

350

Thr Cys 365

Glu Ser

Leu Asp

Lys Ser

Glu Ala

430

Gly Lys 445 ctgtaggaga cctggtatca tgcaaagtgg caatcagcag acccgtacac

Lys Thr

Ser Val

Lys Cys

320

Ile Ser

335

Pro Pro

Leu Val

Asn Gly

Ser Asp

400

Arg Trp 415

Leu His cagagtcacc gcaaaaacca ggtcccatca cctgcagcct ttttggccag

120

180

240

300

- 624 044746 gggaccaagc tctgatgagc cccagagagg gagagtgtca ctgagcaaag ctgagctcgc tggagatcaa agttgaaatc ccaaagtaca cagagcagga cagactacga ccgtcacaaa acgaactgtg tggaactgcc gtggaaggtg cagcaaggac gaaaca caaa gagcttcaac gctgcaccat tctgttgtgt gataacgccc agcacctaca gtctacgcct aggggagagt ctgtcttcat gcctgctgaa tccaatcggg gcctcagcag gcgaagtcac gttag cttcccgcca taacttctat taactcccag caccctgacg ccatcagggc

360

420

480

540

600

645 <210> 792 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 792

Asp Ile 1

Gln Leu

Thr Gln 5

Ser Pro

Ser Phe

Leu Ser

Ala Ser

Asp Arg

Val Thr

Ile Thr

Cys Trp

Ala Ser 25

Gln Gly

Ile Ser

Leu Ala

Trp Tyr 35

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

Lys Leu 45

Tyr Ala 50

Ala Ser

Thr Leu

Gln Ser 55

Gly Val

Pro Ser

Arg Phe

Ser Gly 65

Ser Gly

Thr Glu

Phe Thr

Leu Thr

Ile Ser 75

Ser Leu

Glu Asp

Phe Ala

Thr Tyr 85

Tyr Cys

Gln Leu

Leu Asn

Ser Tyr

Thr Phe

Gly Gln

100

Gly Thr

Lys Leu

Glu Ile 105

Lys Arg

Thr Val

110

Pro Ser

Val Phe 115

Ile Phe

Pro Pro

120

Ser Asp

Glu Gln

Leu Lys 125

Thr Ala

130

Ser Val

Val Cys

Leu Leu 135

Asn Asn

Phe Tyr

140

Pro Arg

Lys Val 145

Gln Trp

Lys Val

150

Asp Asn

Ala Leu

Gln Ser 155

Gly Asn

Val Gly 15

Ser Tyr

Leu Ile

Ser Gly

Glin Pro 80

Pro Tyr 95

Ala Ala

Ser Gly

Glu Ala

Ser Gln

160

- 625 044746

Glu Ser Val Thr

Glu Gln Asp Ser Lys Asp

165 170

Ser Thr Leu Thr

180

Leu Ser Lys Ala Asp Tyr

185

Ala Cys Glu Val

195

Thr His Gln Gly Leu Ser

200

Ser Thr Tyr Ser Leu Ser 175

Glu Lys His Lys Val Tyr 190

Ser Pro Val Thr Lys Ser 205

Phe Asn Arg Gly Glu Cys

210

<210> 793 <211> 1329 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 793 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt cattgtcagt aggaactaca tgagctggggt ccgccaggct 120 ccagggaagg gactggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgctt caccattctcc cgacacaatt ccaagaacac gctgtatctt 240 caaatgaaca gcctgaaagc tgaggacacg gccgtgtatt actgtgcgag agagctacga 300 gggtactttg actactgggg ccagggaacc ctggtcaccg tctcctcagc ctccaccaag 360 ggcccatcgg tcttccccct ggcgccctgc tccaggagca cctccgagag cacagccgcc 420 ctggggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 480 gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 540 ctcagcagcg tggtgaccgt gccctccagc agcttggggca cgaagaccta cacctgcaac 600 gtagatcaca agccagcaa caccaaggtg gacaagag ttgagtccaa atatggtccc 660 ccatgcccac cgtgcccagc accaggcggt ggcggaccat cagtcttcct gttcccccca 720 aaacccaagg acactctcat gatctcccgg acccctgagg tcacgtgcgt ggtggtggac 780 gtgagccagg aagaccccga ggtccagttc aactggtacg tggatggcgt ggaggtgcat 840 aatgccaaga caaagccgcg ggagaggagcag ttcaacagca cgtaccgtgt ggtcagcgtc 900 ctcaccgtcc tgcaccagga ctggctgaac ggcaagggagt acaagtgcaa ggtctccaac 960 aaaggcctcc cgtcctccat cgagaaaacc atctccaaag ccaaagggca gccccgagag 1020 ccacaggtgt acaccctgcc cccaccag gaggagatga ccaagaacca ggtcagcctg 1080 acctgcctgg tcaaaggctt ctaccccagc gacatcgccg tggagtggga gagcaatggg 1140

- 626 044746 cagccggaga ctctacagca tccgtgatgc ggtaaatga acaactacaa ggctcaccgt atgaggctct gaccacgcct ggacaagagc gcacaaccac cccgtgctgg aggtggcagg tacacacaga actccgacgg aggggaatgt agtccctctc ctccttcttc cttctcat gc cctgtctctg

1200

1260

1320

1329 <210> 794 <211> 442 <212> PROTEIN <213> Artificial sequence <220>

< 223 > Synthetic < 400 > 794

Glu Val 1

Gln Leu

Val Glu 5

Ser Gly

Gly Gly 10

Leu Val

Glin Pro

Ser Leu

Arg Leu 20

Ser Cys

Ala Ala

Ser Gly 25

Phe Ile

Val Ser

Tyr Met

Ser Trp 35

Val Arg

Gln Ala

Pro Gly

Lys Gly

Leu Glu 45

Ser Val

Ile Tyr

Ser Gly

Gly Ser 55

Thr Phe

Tyr Ala 60

Asp Ser

Gly Gly 15

Arg Asn

Trp Val

Val Lys

Gly Arg 65

Phe Thr

Ile Ser

Arg His

Asn Ser

Lys Asn 75

Thr Leu

Tyr Leu 80

Gln Met

Asn Ser

Leu Lys 85

Ala Glu

Asp Thr

Ala Val

Tyr Tyr

Cys Ala 95

Arg Glu

Leu Arg

100

Gly Tyr

Phe Asp

Tyr Trp 105

Gly Gln

Gly Thr

110

Leu Val

Thr Val

Ser Ser 115

Ala Ser

Thr Lys

120

Gly Pro

Ser Val

Phe Pro 125

Leu Ala

Pro Cys

130

Ser Arg

Ser Thr

Ser Glu 135

Ser Thr

Ala Ala

140

Leu Gly

Cys Leu

Val Lys 145

Asp Tyr

Phe Pro

150

Glu Pro

Val Thr

Val Ser

155

Trp Asn

Ser Gly

160

Ala Leu

Thr Ser

Gly Val 165

His Thr

Phe Pro

170

Ala Val

Leu Gln

Ser Ser 175

- 627 044746

Gly

Gly

Lys

Cys 225

Lys

Val

Tyr

Glu

His 305

Lys

Gln

Met

Pro

Asn 385

Leu

Val

Leu Tyr

Thr Lys

195

Val Asp 210

Pro Ala

Pro Lys

Val Val

Val Asp

275

Gln Phe

290

Gln Asp

Gly Leu

Pro Arg

Thr Lys

355

Ser Asp 370

Tyr Lys

Tyr Ser

Phe Ser

Ser Leu 180

Thr Tyr

Lys Arg

Pro Gly

Asp Thr

245

Asp Val 260

Gly Val

Asn Ser

Trp Leu

Pro Ser

325

Glu Pro 340

Asn Gln

Ile Ala

Thr Thr

Arg Leu

405

Cys Ser 420

Ser Ser

Thr Cys

Val Glu

215

Gly Gly 230

Leu Met

Ser Gln

Glu Val

Thr Tyr

295

Asn Gly 310

Ser Ile

Gln Val

Val Ser

Val Glu

375

Pro Pro 390

Thr Val

Val Met

Val Val 185

Asn Val 200

Ser Lys

Gly Pro

Ile Ser

Glu Asp

265

His Asn 280

Arg Val

Lys Glu

Glu Lys

Tyr Thr

345

Leu Thr 360

Trp Glu

Val Leu

Asp Lys

His Glu

425

Thr Val

Pro Ser

Asp His

Lys Pro

205

Tyr Gly

Pro Pro 220

Ser Val

235

Phe Leu

Ser Ser 190

Ser Asn

Cys Pro

Phe Pro

Arg Thr 250

Pro Glu

Val Thr

255

Pro Glu

Ala Lys

Val Ser

Tyr Lys

315

Thr Ile 330

Leu Pro

Cys Leu

Ser Asn

Asp Ser

395

Ser Arg 410

Ala Leu

Val Gln

Phe Asn 270

Thr Lys

285

Pro Arg

Val Leu 300

Thr Val

Cys Lys

Ser Lys

Pro Ser

Val Lys

365

Gly Gln 380

Asp Gly

Trp Gln

His Asn

Val Ser

Ala Lys

335

Gln Glu 350

Gly Phe

Pro Glu

Ser Phe

Glu Gly

415

His Tyr 430

Leu

Thr

Pro

Pro 240

Cys

Trp

Glu

Leu

Asn 320

Gly

Glu

Tyr

Asn

Phe 400

Asn

Thr

- 628 044746

Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435440 <210>795 <211>351 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 795

gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt caccgtcagt agtaactaca tgacctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccgagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctagca 300 gcagctggta cagactactg gggccaggga gccctggtca ccgtctcctc a 351

<210> 796 <211> 117 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>796

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 1015

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn 20 2530

Tyr Met Thr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 4045

Ser Val Ile Tyr Ser Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys 50 5560

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Glu Asn Thr Leu Tyr Leu 65 70 7580

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala 85 9095

Arg Asp Leu Ala Ala Ala Gly Thr Asp Tyr Trp Gly Gln Gly Ala Leu

- 629 044746

100

105

110

Val Thr Val Ser Ser

115 <210> 797 <211> 33 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>797 gcgagagatc tagcagcagc tggtacagac tac33 <210>798 <211>11 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>798

Ala Arg Asp Leu Ala Ala Ala Gly Thr Asp Tyr

510 < 210> 799 < 211> 321 < 212> DNA < 213> Artificial sequence <220>

<223> Synthetic <400>799 gacatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc60 atcacttgct gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca120 gggaaagccc ctaagctcct gatctatgct gcatccactt tg caaagtgg ggtcccatca180 aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct240 gatgattttg caacttatta ctgtcaacac cttaatagtt acctgtacac ttttggccag300 gggaccaagc tggagatcaa a321 <210>

<211>

<212>

<213>

800

107

PROTEIN

Artificial sequence <220>

<223>

Synthetic

- 630 044746 <400>800

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

5 1015

Asp Arg Val Thr Ile Thr Cys Trp Ala Ser Gln Gly Ile Ser Ser Tyr 20 2530

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln His Leu Asn Ser Tyr Leu Tyr 85 9095

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100105 <210>801 <211>27 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>801 caacacctta atagttacct gtacact <210>802 <211>9 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400>802

Gln His Leu Asn Ser Tyr Leu Tyr Thr <210>803 <211>1344 <212> DNA <213> Artificial sequence <220>

<223> Synthetic

- 631 044746

<400> 803 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt caccgtcagt agtaactaca tgacctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccgagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctagca 300 gcagctggta cagactactg gggccaggga gccctggtca ccgtctcctc agcctccacc 360 aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc 600 aacgtgaatc acaagcccag caacaccaag gtggacaaga aagttgagcc caaatcttgt 660 gacaaaactc acacatgccc accgtgccca gcacctgaac tcctgggggg accgtcagtc 720 ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 780 tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 840 ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 900 cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 960 tgcaaggtct ccaacaaagc cctcccagcc ccatcgaga aaaccatctc caaagccaaa 1020 gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 1080 aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1140 tggggagagca atggggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1200 gacggctcct tcttcctcta cagcaagctc accgtggac agagcaggtg gcagcagggg 1260 aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagtcc 1320 ctctccctgt ctccgggtaa atga 1344

<210> 804 <211> 447 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 804

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

5 10 15

- 632 044746

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Phe Thr Val Ser Ser

Tyr Met Thr Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Ser Val Ile Tyr Ser 50

Gly Gly Ser Thr Phe 55

Tyr Ala Asp Ser Val 60

Gly Arg Phe Thr Ile 65

Ser Arg His Asn Ser 70

Glu Asn Thr Leu Tyr 75

Gln Met Asn Ser Leu

Arg Ala Glu Asp Thr 90

Ala Val Tyr Tyr Cys 95

Arg Asp Leu Ala Ala

100

Ala Gly Thr Asp Tyr

105

Trp Gly Gln Gly Ala

110

Val Thr Val Ser Ser

115

Ala Ser Thr Lys Gly 120

Pro Ser Val Phe Pro

125

Ala Pro Ser Ser Lys 130

Ser Thr Ser Gly Gly

135

Thr Ala Ala Leu Gly 140

Leu Val Lys Asp Tyr 145

Phe Pro Glu Pro Val 150

Thr Val Ser Trp Asn 155

Gly Ala Leu Thr Ser

165

Gly Val His Thr Phe

170

Pro Ala Val Leu Gln

175

Ser Gly Leu Tyr Ser

180

Leu Ser Ser Val Val

185

Thr Val Pro Ser Ser

190

Leu Gly Thr Gln Thr

195

Tyr Ile Cys Asn Val

200

Asn His Lys Pro Ser 205

Thr Lys Val Asp Lys

210

Lys Val Glu Pro Lys

215

Ser Cys Asp Lys Thr

220

Thr Cys Pro Pro Cys 225

Pro Ala Pro Glu Leu 230

Leu Gly Gly Pro Ser 235

Phe Leu Phe Pro Pro

245

Lys Pro Lys Asp Thr

250

Leu Met Ile Ser Arg

255

Pro Glu Val Thr Cys

260

Val Val Val Asp Val

265

Ser His Glu Asp Pro

270

Asn

Val

Lys

Leu 80

Ala

Leu

Leu

Cys

Ser 160

Ser

Ser

Asn

His

Val 240

Thr

Glu

- 633 044746

Val Lys

Thr Lys

290

Val Leu 305

Cys Lys

Phe Asn 275

Pro Arg

Thr Val

Val Ser

Trp Tyr

Glu Glu

Leu His

310

Asn Lys 325

Ser Lys

Ala Lys

340

Gly Gln

Pro Ser

Arg Asp 355

Glu Leu

Val Asp

280

Gln Tyr 295

Gln Asp

Ala Leu

Pro Arg

Thr Lys

360

Gly Val

Asn Ser

Trp Leu

Pro Ala

330

Glu Pro 345

Asn Gln

Glu Val

Thr Tyr

300

Asn Gly 315

Pro Ile

Gln Val

Val Ser

Val Lys

370

Gly Phe

Tyr Pro

Ser Asp 375

Ile Ala

Val Glu

380

Gly Gln 385

Pro Glu

Asn Asn

390

Tyr Lys

Thr Thr

Pro Pro 395

Asp Gly

Ser Phe

Phe Leu 405

Tyr Ser

Lys Leu

410

Thr Val

Trp Gln

Gln Gly

420

Asn Val

Phe Ser

Cys Ser 425

Val Met

His Asn

His Tyr 435

Thr Gln

Lys Ser

440

Leu Ser

Leu Ser <210>

<211>

<212>

<213>

805

645

DNA

Artificial sequence

Synthetic

805 <220>

<223>

<400>

gacatccagt atcacttgct gggaaagccc aggttcagcg gatgattttg tgacccagtc gggccagtca ctaagctcct gcagtggatc caacttatta tccatccttc gggcattagc gatctatgct tgggacagaa ctgtcaacac ctgtctgcat agttatttag gcatccactt ttcactctca ct taatagtt

His Asn 285

Arg Val

Lys Glu

Glu Lys

Tyr Thr

350

Leu Thr 365

Trp Glu

Val Leu

Asp Lys

His Glu

430

Pro Gly 445 ctgtaggaga cctggtatca tgcaaagtgg caatcagcag acctgtacac

Ala Lys

Val Ser

Tyr Lys

320

Thr Ile 335

Leu Pro

Cys Leu

Ser Asn

Asp Ser

400

Ser Arg 415

Ala Leu

Lys cagagtcacc gcaaaaacca ggtcccatca cctgcagcct ttttggccag

120

180

240

300

- 634 044746 gggaccaagc tctgatgagc cccagagagg gagagtgtca ctgagcaaag ctgagctcgc tggagatcaa agttgaaatc ccaaagtaca cagagcagga cagactacga ccgtcacaaa acgaactgtg tggaactgcc gtggaaggtg cagcaaggac gaaaca caaa gagcttcaac gctgcaccat tctgttgtgt gataacgccc agcacctaca gtctacgcct aggggagagt ctgtcttcat gcctgctgaa tccaatcggg gcctcagcag gcgaagtcac gttag cttcccgcca taacttctat taactcccag caccctgacg ccatcagggc

360

420

480

540

600

645 <210> 806 <211> 214 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 806

Asp Ile 1

Gln Leu

Thr Gln 5

Ser Pro

Ser Phe

Leu Ser

Ala Ser

Asp Arg

Val Thr

Ile Thr

Cys Trp

Ala Ser 25

Gln Gly

Ile Ser

Leu Ala

Trp Tyr 35

Gln Gln

Lys Pro 40

Gly Lys

Ala Pro

Lys Leu 45

Tyr Ala 50

Ala Ser

Thr Leu

Gln Ser 55

Gly Val

Pro Ser

Arg Phe

Ser Gly 65

Ser Gly

Thr Glu

Phe Thr

Leu Thr

Ile Ser 75

Ser Leu

Asp Asp

Phe Ala

Thr Tyr 85

Tyr Cys

Gln His

Leu Asn

Ser Tyr

Thr Phe

Gly Gln

100

Gly Thr

Lys Leu

Glu Ile 105

Lys Arg

Thr Val

110

Pro Ser

Val Phe 115

Ile Phe

Pro Pro

120

Ser Asp

Glu Gln

Leu Lys 125

Thr Ala

130

Ser Val

Val Cys

Leu Leu 135

Asn Asn

Phe Tyr

140

Pro Arg

Lys Val 145

Gln Trp

Lys Val

150

Asp Asn

Ala Leu

Gln Ser 155

Gly Asn

Val Gly 15

Ser Tyr

Leu Ile

Ser Gly

Glin Pro 80

Leu Tyr 95

Ala Ala

Ser Gly

Glu Ala

Ser Gln

160

- 635 044746

Glu

Ser

Val

Thr

Glu

165

Gln

Asp

Ser

Lys

Asp

170

Ser

Thr

Tyr

Ser

Leu

175

Ser

Ser

Thr

Leu

Thr

180

Leu

Ser

Lys

Ala

Asp

185

Tyr

Glu

Lys

His

Lys 190

Val

Tyr

Ala

Cys

Glu

195

Val

Thr

His

Gln

Gly 200

Leu

Ser

Ser

Pro

Val

205

Thr

Lys

Ser

Phe Asn Arg Gly Glu Cys

210

<210> 807 <211> 1332 <212>DNA < 213> Artificial sequence <220> < 223> Synthetic <400> 807 gaggtgcagc tggtggagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60 tcctgtgcag cctctggggtt caccgtcagt agtaactaca tgacctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac attctacgca 180 gactccgtga aggggccgatt caccattctcc agacacaatt ccgagaacac gctgtatctt 240 caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctagca 300 gcagctggta cagactactg gggccaggga gccctggtca ccgtctcctc agcctccacc 360 aagggcccat cggtcttccc cctggcgccc tgctccagga gcacctccga gagcacagcc 420 gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 480 ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 540 tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacgaagac ctacacctgc 600 aacgtagatc acaagcccag caacaccaag gtggacaaga gagttgagtc caaatatggt 660 ccccatgcc caccgtgccc agcaccaggc ggtggcggac catcagtctt cctgttcccc 720 ccaaaaccca aggacactct catgatctcc cggacccctg aggtcacgtg cgtggtggtg 780 gacgtgagcc aggaagacc cgaggtccag ttcaactggt acgtggatgg cgtggaggtg 840 cataatgcca agacaaagcc gcgggaggag cagttcaaca gcacgtaccg tgtggtcagc 900 gtcctcaccg tcctgcacca ggactggctg aacggcaagg agtacaagtg caaggtctcc 960 aacaaaggcc tcccgtcctc catcgagaaa accatctcca aagccaaagg gcagccccga 1020 gagccacagg tgtacaccct gcccccatcc caggagaga tgaccaagaa ccaggtcagc 1080 ctgacctgcc tggtcaaagg cttctacccc agcgacatcg ccgtggagtg ggagagcaat 1140

- 636 044746 gggcagccgg ttcctctaca tgctccgtga ctgggtaaat agaacaacta gcaggctcac tgcatgaggc ga caagaccacg cgtggacaag tctgcacaac cctcccgtgc agcaggtggc cactacacac tggactccga aggaggggaa agaagtccct cggctccttc t gtcttctca ctccctgtct

1200

1260

1320

1332 <210> 808 <211> 443 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 808

Glu Val Gln 1

Leu Val Glu Ser Gly Gly 5

Gly Leu Val Gln Pro 10

Ser Leu Arg

Leu Ser Cys Ala Ala Ser

25

Gly Phe Thr Val Ser 30

Gly Gly 15

Ser Asn

Tyr Met Thr

Trp Val Arg Gln Ala Pro 40

Gly Lys Gly Leu Glu 45

Trp Val

Ser Val Ile Tyr 50

Ser

Gly Gly Ser Thr Phe Tyr Ala Asp Ser Val Lys

60

Gly Arg Phe Thr 65

Ile

Ser Arg His Asn Ser Glu Asn Thr Leu Tyr Leu

75 80

Gln Met

Asn Ser

Arg Asp

Leu Ala

100

Val Thr

Val Ser

115

Ala Pro

130

Cys Ser

Leu Arg 85

Ala Ala

Ser Ala

Arg Ser

Ala Glu

Asp Thr

Ala Val

Tyr Tyr

Gly Thr

Ser Thr

120

Thr Ser 135

Asp Tyr 105

Trp Gly

Gln Gly

110

Lys Gly

Glu Ser

Pro Ser

Thr Ala

140

Val Phe 125

Ala Leu

Cys Ala 95

Ala Leu

ProLeu

Gly Cys

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

145 150 155 160

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

165 170 175

- 637 044746

Ser

Leu

Thr

Pro 225

Pro

Cys

Trp

Glu

Leu 305

Asn

Gly

Glu

Tyr

Asn 385

Phe

Asn

Gly Leu Tyr

180

Gly Thr Lys

195

Lys Val Asp 210

Cys Pro Ala

Lys Pro Lys

Val Val Val

260

Tyr Val Asp

275

Glu Gln Phe 290

His Gln Asp

Lys Gly Leu

Gln Pro Arg

340

Met Thr Lys

355

Pro Ser Asp 370

Asn Tyr Lys

Leu Tyr Ser

Val Phe Ser

420

Ser Leu Ser

Thr Tyr Thr

Lys Arg Val

215

Pro Gly Gly

230

Asp Thr Leu 245

Asp Val Ser

Gly Val Glu

Asn Ser Thr

295

Trp Leu Asn

310

Pro Ser Ser 325

Glu Pro Gln

Asn Gln Val

Ile Ala Val

375

Thr Thr Pro

390

Arg Leu Thr 405

Cys Ser Val

Ser Val Val

185

Cys Asn Val 200

Glu Ser Lys

Gly Gly Pro

Met Ile Ser

250

Gln Glu Asp

265

Val His Asn 280

Tyr Arg Val

Gly Lys Glu

Ile Glu Lys

330

Val Tyr Thr

345

Ser Leu Thr 360

Glu Trp Glu

Pro Val Leu

Val Asp Lys

410

Met His Glu

425

Thr Val Pro

Ser Ser Ser 190

Asp His Lys

205

Pro Ser Asn

Tyr Gly Pro

220

Ser Val Phe 235

Arg Thr Pro

Pro Glu Val

Ala Lys Thr

285

Val Ser Val

300

Tyr Lys Cys 315

Thr Ile Ser

Leu Pro Pro

Cys Leu Val

365

Ser Asn Gly

380

Asp Ser Asp 395

Ser Arg Trp

Ala Leu His

Pro Cys Pro

Leu Phe Pro

240

Glu Val Thr

255

Gln Phe Asn 270

Lys Pro Arg

Leu Thr Val

Lys Val Ser

320

Lys Ala Lys

335

Ser Gln Glu 350

Lys Gly Phe

Gln Pro Glu

Gly Ser Phe

400

Gln Glu Gly 415

Asn His Tyr 430

- 638 044746

Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys

435440 <210>809 <211>360 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>809 caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc60 tcctgtgcag cctctggatt caccttcagt agctatggca tgcactgggt ccgccaggct120 ccaggcaagg ggctggagtg ggtggcagtt at atcatatg atggaagtta taagtactat180 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat240 ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gatagatggg300 gggacagtga ctacgatttt tgactactgg ggccagggaa ccctggtcac cgtctcctca360 <210>810 <211 >120 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 810

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Ser Ser Tyr 25 30

Gly Met His Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ala Val Ile Ser Tyr Asp Gly Ser

55

Tyr Lys Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ser Lys Asn Thr Leu Tyr

80

Leu Gln Met Asn Ser Leu Arg Ala 85

Glu Asp Thr Ala Val Tyr Tyr Cys

95

Ala Ile Asp Gly Gly Thr Val Thr

Thr Ile Phe Asp Tyr Trp Gly Gln

- 639 044746

100

105

110

Gly Thr Leu Val Thr Val Ser Ser

115120 <210>811 <211>24 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>811 ggattcacct tcagtagcta tggc24 <210>812 <211>8 <212> PROTEIN <213>Artificial sequence <220>

< 223> Synthetic < 400>812

Gly Phe Thr Phe Ser Ser Tyr Gly < 210 > 813 < 211 > 24 < 212 > DNA < 213 > Artificial sequence < 220 >

< 223> Synthetic < 400>813 atatcatatg atggaagtta taag24 < 210>814 < 211>8 < 212> PROTEIN < 213> Artificial sequence <220>

< 223> Synthetic < 400>814

Ile Ser Tyr Asp Gly Ser Tyr Lys <210>815 <211>39 <212> DNA <213> Artificial sequence

- 640 044746 gcgatagatg gggggacagt gactacgatt tttgactac <220>

<223> Synthetic <400>815 <210>816 <211>13 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>816

Ala Ile Asp Gly Gly Thr Val Thr Thr Ile Phe Asp Tyr

510 <210>817 <211>324 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 817 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca gggaaagccc ctaagctcct gatctatact gcatccagtt tgcaaagtgg gg tcccatca aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct gaagattttg caacttacta ctgtcaacag agttacagta cccctccgtg gacgttcggc caagggacca aggtggaaat caaa

120

180

240

300

324 <210> 818 <211> 108 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 818

Asp

Ile

Gln

Met

Thr 5

Gln

Ser

Pro

Ser

Ser 10

Leu

Ser

Ala

Ser

Val 15

Gly

Asp

Arg

Val

Thr 20

Ile

Thr

Cys

Arg

Ala 25

Ser

Gln

Ser

Ile

Ser 30

Ser

Tyr

Leu

Asn

Trp

Tyr

Gln

Gln

Lys

Pro

Gly

Lys

Ala

Pro

Lys

Leu

Leu

Ile

- 641 044746

Tyr Thr Ala 50 Ser Ser Leu Gln 55 Ser Gly Val Pro Ser 60 Arg Phe Ser Gly Ser Gly Ser 65 Gly Thr Asp 70 Phe Thr Leu Thr Ile 75 Ser Ser Leu Gln Pro 80 Glu Asp Phe Ala Thr 85 Tyr Tyr Cys Gln Gln 90 Ser Tyr Ser Thr Pro 95 Pro Trp Thr Phe Gly 100 Gln Gly Thr Lys Val 105 Glu Ile Lys <210> 819 <211> 9 <212> DNA <213> Artificial subsequence <220> <223> Synthetic <400> 819 actngcatcc

<210> 820 <211> 3 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>820

Thr Ala Ser <210>821 <211>30 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>821 caacagagtt acagtacccc tccgtggacg <210>822 <211>10 <212> PROTEIN <213> Artificial sequence <220>

- 642 044746 <223> Synthetic <400>822

Gln Gln Ser Tyr Ser Thr Pro Pro Trp Thr <210>823 <211>1353 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400>823 caggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc60 tcctgtgcag cctctggatt caccttcagt agctatggca tgcactgggt ccgccaggct120 ccaggcaagg ggctggagtg ggtggcagt t atatcatatg atggaagtta taagtactat180 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat240 ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gatagatggg300 gggacagtga ctacgatttt tgactactgg ggccagg gaa ccctggtcac cgtctcctca360 gcctccacca agggcccatc ggtcttcccc ctggcaccct cctccaagag cacctctggg420 ggcacagcgg ccctgggctg cctggtcaag gactacttcc ccgaaccggt gacggtgtcg480 tggaactcag gcgccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca540 ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600 tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc660 aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctgaact cctgggggga720 ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccc t780 gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg840 tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacaac900 agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag960 gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc1020 aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag1080 ctgaccaaga accaggtcag cctgacctgc ctggtcaaag gcttctatcc cagcgacatc1140 gccgtggagt gggagagcaa tgggcagccg gagaacaact acaagaccac gcctcccgtg1200 ctggactccg acggctcctt cttcctctac agcaagctca ccgtggacaa gagcaggtgg1260 cagcagggga acg tcttctc atgctccgtg atgcatgagg ctctgcacaa ccactacacg1320 cagaagtccc tctccctgtc tccgggtaaa tga1353

- 643 044746 <210> 824 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 824

Gln Val Gln Leu Val

5

Glu Ser Gly Gly Gly

Val Val Gln Pro Gly

Ser Leu Arg Leu Ser 20

Cys Ala Ala Ser Gly

Phe Thr Phe Ser Ser

Gly Met His Trp Val 35

Arg Gln Ala Pro Gly 40

Lys Gly Leu Glu Trp 45

Ala Val Ile Ser Tyr 50

Asp Gly Ser Tyr Lys 55

Tyr Tyr Ala Asp Ser 60

Lys Gly Arg Phe Thr 65

Ile Ser Arg Asp Asn 70

Ser Lys Asn Thr Leu 75

Leu Gln Met Asn Ser

Leu Arg Ala Glu Asp 90

Thr Ala Val Tyr Tyr 95

Ala Ile Asp Gly Gly

100

Thr Val Thr Thr Ile

105

Phe Asp Tyr Trp Gly

110

Gly Thr Leu Val Thr 115

Val Ser Ser Ala Ser

120

Thr Lys Gly Pro Ser

125

Phe Pro Leu Ala Pro

130

Ser Ser Lys Ser Thr 135

Ser Gly Gly Thr Ala 140

Leu Gly Cys Leu Val 145

Lys Asp Tyr Phe Pro 150

Glu Pro Val Thr Val 155

Trp Asn Ser Gly Ala

165

Leu Thr Ser Gly Val

170

His Thr Phe Pro Ala

175

Leu Gln Ser Ser Gly

180

Leu Tyr Ser Leu Ser

185

Ser Val Val Thr Val

190

Ser Ser Ser Leu Gly 195

Thr Gln Thr Tyr Ile 200

Cys Asn Val Asn His

205

Arg

Tyr

Val

Val

Tyr 80

Cys

Gln

Val

Ala

Ser 160

Val

Pro

Lys

- 644 044746

Pro

Lys 225

Pro

Ser

Asp

Asn

Val 305

Glu

Lys

Thr

Thr

Glu 385

Leu

Lys

Glu

Gly

Ser Asn Thr 210

Thr His Thr

Ser Val Phe

Arg Thr Pro

260

Pro Glu Val

275

Ala Lys Thr 290

Val Ser Val

Tyr Lys Cys

Thr Ile Ser

340

Leu Pro Pro

355

Cys Leu Val 370

Ser Asn Gly

Asp Ser Asp

Ser Arg Trp

420

Ala Leu His

435

Lys 450

Lys Val Asp

215

Cys Pro Pro

230

Leu Phe Pro 245

Glu Val Thr

Lys Phe Asn

Lys Pro Arg

295

Leu Thr Val

310

Lys Val Ser 325

Lys Ala Lys

Ser Arg Asp

Lys Gly Phe

375

Gln Pro Glu

390

Gly Ser Phe 405

Gln Gln Gly

Asn His Tyr

Lys Lys Val

Cys Pro Ala

Pro Lys Pro

250

Cys Val Val

265

Trp Tyr Val 280

Glu Glu Gln

Leu His Gln

Asn Lys Ala

330

Gly Gln Pro

345

Glu Leu Thr 360

Tyr Pro Ser

Asn Asn Tyr

Phe Leu Tyr

410

Asn Val Phe

425

Thr Gln Lys 440

Glu Pro Lys

220

Pro Glu Leu 235

Lys Asp Thr

Val Asp Val

Asp Gly Val

285

Tyr Asn Ser

300

Asp Trp Leu 315

Leu Pro Ala

Arg Glu Pro

Lys Asn Gln

365

Asp Ile Ala

380

Lys Thr Thr 395

Ser Lys Leu

Ser Cys Ser

Ser Leu Ser

445

Ser Cys Asp

Leu Gly Gly

240

Leu Met Ile

255

Ser His Glu 270

Glu Val His

Thr Tyr Arg

Asn Gly Lys

320

Pro Ile Glu

335

Gln Val Tyr 350

Val Ser Leu

Val Glu Trp

Pro Pro Val

400

Thr Val Asp

415

Val Met His 430

Leu Ser Pro

- 645 044746 <210> 825 <211> 648 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 825

gacatccaga tgaccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60 atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120 gggaaagccc ctaagctcct gatctatact gcatccagtt tgcaaagtgg ggtcccatca 180 aggttcagtg gcagtggatc tggacagat ttcactctca ccatcagcag tctgcaacct 240 gaagatttg caactacta ctgtcaacag agttacagta cccctccgtg gacgttcggc 300 caagggacca aggtggaaat caaacgaact gtggctgcac catctgtctt catcttcccg 360 ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 420 tatccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 480 caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 540 acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 600 ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgttag 648

<210> 826 <211> 215 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400>826

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

5 1015

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr 20 2530

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile 35 4045

Tyr Thr Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly 50 5560

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro 65 70 7580

- 646 044746

Glu Asp

Phe Ala

Trp Thr

Phe Gly

100

Ala Pro

Ser Val 115

Gly Thr

130

Ala Ser

Thr Tyr 85

Gln Gly

Phe Ile

Val Val

Tyr Cys

Thr Lys

Phe Pro

120

Cys Leu 135

Gln Gln

Val Glu 105

Pro Ser

Leu Asn

Ser Tyr

Ile Lys

Asp Glu

Asn Phe

140

Ser Thr

Arg Thr

110

Gln Leu 125

Tyr Pro

Ala Lys 145

Val Gln

Trp Lys

150

Val Asp

Asn Ala

Leu Gln 155

Ser Gly

Gln Glu

Ser Val

Thr Glu 165

Gln Asp

Ser Lys

170

Asp Ser

Thr Tyr

Ser Ser

Thr Leu

180

Thr Leu

Ser Lys

Ala Asp 185

Tyr Glu

Lys His

190

Tyr Ala

Cys Glu 195

Val Thr

His Gln

200

Gly Leu

Ser Ser

Pro Val 205

Pro Pro 95

Val Ala

Lys Ser

Arg Glu

Asn Ser 160

Ser Leu 175

Lys Val

Thr Lys

Ser Phe Asn Arg Gly Glu

210

Cys 215 <210> 827 <211> 1341 <212> DNA <213> Artificial sequence <220>

<223> Synthetic <400> 827 caggtgcagc tcctgtgcag ccaggcaagg gcagactccg ctgcaaatga gggacagtga gcctccacca agcacagccg tggaactcag tggtggagtc cctctggatt ggctggagtg tgaagggccg acagcctgag ctacgatttt agggcccatc ccct gggctg gcgccctgac tgggggaggc caccttcagt ggtggcagtt attcaccatc agctgaggac tgactactgg ggtcttcccc cctggtcaag cagcggcgtg gtggtccagc agctatggca atatcatatg tccagagaca acggctgtgt ggccagggaa ctggcgccct gactacttcc cacacctt cc ctgggaggtc tgcactgggt atggaagtta attccaagaa attactgtgc ccctggtcac gctccaggag ccgaaccggt cggctgtcct cctgagactc ccgccaggct taagtactat cacgctgtat gatagatggg cgtctcctca cacctccgag gacggtgtcg acagtcctca

120

180

240

300

360

420

480

540

- 647 044746

ggactactact ccctcagcag cgtggtgacc gtgccctcca gcagcttgggg cacgaagacc 600 tacacctgca acgtagatca caagcccagc aacaccaagg tggacaagag agttgagtcc 660 aaatatggtc ccccatgccc accgtgccca gcaccaggcg gtggcggacc atcagtcttc 720 ctgttccccc caaaacccaa ggacactctc atgatctccc ggacccctga ggtcacgtgc 780 gtggtggtgg acgtgagcca ggaagacccc gaggtccagt tcaactggta cgtggatggc 840 gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agttcaacag cagtaccgt 900 gtggtcagcg tcctcaccgt cctgcaccag gactggctga acggcaagga gtacaagtgc 960 aaggtctcca acaaaggcct cccgtcctcc atcgagaaaa ccatctccaa agccaaaggg 1020 cagccccgag agccacaggt gtacaccctg ccccatccc aggaggat gaccaagaac 1080 caggtcagcc tgacctgcct ggtcaaaggc ttctacccca gcgacatcgc cgtggagtgg 1140 gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1200 ggctccttct tcctctacag caggctcacc gtggacaaga gcaggtggca ggaggggaat 1260 gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacaca gaagtccctc 1320 tccctgtctc tgggtaaatg a 1341

<210> 828 <211> 446 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 828

Gln Val Gln Leu Val Glu Ser Gly 1 5

Gly Gly Val Val Gln Pro Gly Arg

15

Ser Leu Arg Leu Ser Cys Ala Ala 20

Ser Gly Phe Thr Phe Ser Ser Tyr 25 30

Gly Met His Trp Val Arg Gln Ala

40

Pro Gly Lys Gly Leu Glu Trp Val 45

Ala Val Ile Ser Tyr Asp Gly Ser

55

Tyr Lys Tyr Tyr Ala Asp Ser Val 60

Lys Gly Arg Phe Thr Ile Ser Arg 65 70

Asp Asn Ser Lys Asn Thr Leu Tyr

80

Leu Gln Met Asn Ser Leu Arg Ala 85

Glu Asp Thr Ala Val Tyr Tyr Cys

95

- 648 044746

Ala

Gly

Phe

Leu 145

Trp

Leu

Ser

Pro

Pro 225

Leu

Glu

Gln

Lys

Leu 305

Lys

Lys

Ile Asp Gly

100

Thr Leu Val

115

Pro Leu Ala 130

Gly Cys Leu

Asn Ser Gly

Gln Ser Ser

180

Ser Ser Leu

195

Ser Asn Thr 210

Cys Pro Pro

Phe Pro Pro

Val Thr Cys

260

Phe Asn Trp

275

Pro Arg Glu 290

Thr Val Leu

Val Ser Asn

Ala Lys Gly

340

Gly Thr Val

Thr Val Ser

Pro Cys Ser

135

Val Lys Asp

150

Ala Leu Thr 165

Gly Leu Tyr

Gly Thr Lys

Lys Val Asp

215

Cys Pro Ala

230

Lys Pro Lys 245

Val Val Val

Tyr Val Asp

Glu Gln Phe

295

His Gln Asp

310

Lys Gly Leu 325

Gln Pro Arg

Thr Thr Ile

105

Ser Ala Ser 120

Arg Ser Thr

Tyr Phe Pro

Ser Gly Val

170

Ser Leu Ser

185

Thr Tyr Thr 200

Lys Arg Val

Pro Gly Gly

Asp Thr Leu

250

Asp Val Ser

265

Gly Val Glu 280

Asn Ser Thr

Trp Leu Asn

Pro Ser Ser

330

Glu Pro Gln

345

Phe Asp Tyr

Thr Lys Gly

125

Ser Glu Ser

140

Glu Pro Val 155

His Thr Phe

Ser Val Val

Cys Asn Val

205

Glu Ser Lys

220

Gly Gly Pro 235

Met Ile Ser

Gln Glu Asp

Val His Asn

285

Tyr Arg Val

300

Gly Lys Glu 315

Ile Glu Lys

Val Tyr Thr

Trp Gly Gln 110

Pro Ser Val

Thr Ala Ala

Thr Val Ser

160

Pro Ala Val

175

Thr Val Pro 190

Asp His Lys

Tyr Gly Pro

Ser Val Phe

240

Arg Thr Pro

255

Pro Glu Val 270

Ala Lys Thr

Val Ser Val

Tyr Lys Cys

320

Thr Ile Ser

335

Leu Pro Pro 350

- 649 044746

Ser Gln Glu Glu Met

355

Thr Lys Asn Gln Val

360

Ser Leu Thr Cys Leu

365

Lys Gly Phe Tyr Pro

370

Ser Asp Ile Ala Val

375

Glu Trp Glu Ser Asn

380

Gln Pro Glu Asn Asn 385

Tyr Lys Thr Thr Pro 390

Pro Val Leu Asp Ser 395

Gly Ser Phe Phe Leu

405

Tyr Ser Arg Leu Thr

410

Val Asp Lys Ser Arg

415

Gln Glu Gly Asn Val

420

Phe Ser Cys Ser Val

425

Met His Glu Ala Leu

430

Val

Gly

Asp 400

Trp

His

Asn His Tyr Thr Gln 435

Lys Ser Leu Ser Leu 440

Ser Leu Gly Lys

445 <210> 829 <211> 251 <212> PROTEIN <213> Artificial <220>

<223> Synthetic <400> 829

Arg Val Gln Pro Thr

5 sequence

Glu Ser Ile Val Arg

Phe Pro Asn Ile Thr

Leu Cys Pro Phe Gly

Glu Val Phe Asn Ala

Thr Arg Phe Ala Ser 30

Tyr Ala Trp Asn Arg 35

Lys Arg Ile Ser Asn 40

Cys Val Ala Asp Tyr 45

Val Leu Tyr Asn Ser 50

Ala Ser Phe Ser Thr 55

Phe Lys Cys Tyr Gly 60

Ser Pro Thr Lys Leu 65

Asn Asp Leu Cys Phe 70

Thr Asn Val Tyr Ala 75

Ser Phe Val Ile Arg 85

Gly Asp Glu Val Arg 90

Gln Ile Ala Pro Gly 95

Thr Gly Lys Ile Ala

100

Asp Tyr Asn Tyr Lys

105

Leu Pro Asp Asp Phe

110

Asn

Val

Ser

Val

Asp 80

Gln

Thr

- 650 044746

Gly Cys Val Ile Ala 115

Trp Asn Ser Asn Asn

120

Leu Asp Ser Lys Val 125

Gly Asn Tyr Asn Tyr

130

Leu Tyr Arg Leu Phe

135

Arg Lys Ser Asn Leu

140

Pro Phe Glu Arg Asp 145

Ile Ser Thr Glu Ile 150

Tyr Gln Ala Gly Ser 155

Pro Cys Asn Gly Val

165

Glu Gly Phe Asn Cys

170

Tyr Phe Pro Leu Gln

175

Tyr Gly Phe Gln Pro

180

Thr Asn Gly Val Gly

185

Tyr Gln Pro Tyr Arg

190

Val Val Leu Ser Phe

195

Glu Leu Leu His Ala

200

Pro Ala Thr Val Cys

205

Pro Lys Lys Ser Thr 210

Asn Leu Val Lys Asn

215

Lys Cys Val Asn Phe

220

Gln Lys Leu Ile Ser 225

Glu Glu Asp Leu Gly 230

Gly Glu Gln Lys Leu 235

Gly

Lys

Thr 160

Ser

Val

Gly

Glu

Ile 240

Ser Glu Glu Asp Leu

245

His His His His

250

His <210> 830 <211> 456 <212> PROTEIN <213> Artificial <220>

<223> Synthetic <400> 830

Arg Val Gln Pro Thr

5 sequence

Glu Ser Ile Val Arg

Phe Pro Asn Ile Thr

Leu Cys Pro Phe Gly 20

Glu Val Phe Asn Ala

Thr Arg Phe Ala Ser 30

Tyr Ala Trp Asn Arg 35

Lys Arg Ile Ser Asn 40

Cys Val Ala Asp Tyr 45

Val Leu Tyr Asn Ser 50

Ala Ser Phe Ser Thr 55

Phe Lys Cys Tyr Gly 60

Asn

Val

Ser

Val

Asp

Ser Pro Thr Lys Leu

Asn Asp Leu Cys Phe

Thr Asn Val Tyr Ala

- 651 044746

Ser Phe Val Ile Arg 85

Gly Asp Glu Val Arg 90

Gln Ile Ala Pro Gly 95

Thr Gly Lys Ile Ala

100

Asp Tyr Asn Tyr Lys

105

Leu Pro Asp Asp Phe

110

Gly Cys Val Ile Ala 115

Trp Asn Ser Asn Asn

120

Leu Asp Ser Lys Val 125

Gly Asn Tyr Asn Tyr 130

Leu Tyr Arg Leu Phe

135

Arg Lys Ser Asn Leu 140

Pro Phe Glu Arg Asp 145

Ile Ser Thr Glu Ile 150

Tyr Gln Ala Gly Ser 155

Pro Cys Asn Gly Val

165

Glu Gly Phe Asn Cys

170

Tyr Phe Pro Leu Gln

175

Tyr Gly Phe Gln Pro

180

Thr Asn Gly Val Gly

185

Tyr Gln Pro Tyr Arg

190

Val Val Leu Ser Phe

195

Glu Leu Leu His Ala

200

Pro Ala Thr Val Cys

205

Pro Lys Lys Ser Thr 210

Asn Leu Val Lys Asn 215

Lys Cys Val Asn Phe

220

Pro Arg Gly Pro Thr 225

Ile Lys Pro Cys Pro 230

Pro Cys Lys Cys Pro 235

Pro Asn Leu Leu Gly

245

Gly Pro Ser Val Phe

250

Ile Phe Pro Pro Lys

255

Lys Asp Val Leu Met

260

Ile Ser Leu Ser Pro

265

Ile Val Thr Cys Val

270

Val Asp Val Ser Glu

275

Asp Asp Pro Asp Val 280

Gln Ile Ser Trp Phe

285

Asn Asn Val Glu Val

290

His Thr Ala Gln Thr

295

Gln Thr His Arg Glu 300

Tyr Asn Ser Thr Leu 305

Arg Val Val Ser Ala 310

Leu Pro Ile Gln His 315

Gln

Thr

Gly

Lys

Thr 160

Ser

Val

Gly

Glu

Ala 240

Ile

Val

Val

Asp

Gln 320

- 652 044746

Asp

Trp

Met

Ser

Gly 325

Lys

Glu

Phe

Lys

Cys 330

Lys

Val

Asn

Asn

Lys

335

Leu

Pro

Ala

Pro

340

Ile

Glu

Arg

Thr

Ile

345

Ser

Lys

Pro

Lys

Gly 350

Ser

Arg

Ala

Pro

355

Gln

Val

Tyr

Val

Leu

360

Pro

Pro

Pro

Glu

Glu

365

Glu

Met

Lys

Lys 370

Gln

Val

Thr

Leu

Thr

375

Cys

Met

Val

Thr

Asp 380

Phe

Met

Pro

Asp 385

Ile

Tyr

Val

Glu

Trp 390

Thr

Asn

Asn

Gly

Lys 395

Thr

Glu

Leu

Asn

Lys

Asn

Thr

Glu

Pro

405

Val

Leu

Asp

Ser

Asp 410

Gly

Ser

Tyr

Phe

Met

415

Ser

Lys

Leu

Arg 420

Val

Glu

Lys

Lys

Asn

425

Trp

Val

Glu

Arg

Asn

430

Ser

Ser

Cys

Ser

435

Val

Val

His

Glu

Gly 440

Leu

His

Asn

His

His

445

Thr

Thr

Asp

Val

Thr

Glu

Tyr 400

Tyr

Tyr

Lys

Ser

Phe

450

Ser

Arg

Thr

Pro

Gly 455

Lys <210> 831 <211> 450 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 831

Arg Val Gln Pro Thr Glu Ser

5

Ile Val Arg Phe Pro Asn Ile Thr

15

Leu Cys Pro Phe Gly Glu Val 20

Phe Asn Ala Thr Arg Phe Ala Ser

thirty

Tyr Ala Trp Asn Arg Lys Arg 35

Ile Ser Asn Cys Val Ala Asp Tyr 40 45

Val Leu Tyr Asn Ser Ala Ser

55

Phe Ser Thr Phe Lys Cys Tyr Gly 60

Asn

Val

Ser

Val

Asp

Ser Pro Thr Lys Leu Asn Asp

Leu Cys Phe Thr Asn Val Tyr Ala

- 653 044746

Ser

Thr

Gly

Gly

Pro 145

Pro

Tyr

Val

Pro

Lys 225

Pro

Ser

Asp

Asn

Val 305

PheVal

Gly Lys

Cys Val 115

Asn Tyr 130

PheGlu

Cys Asn

Gly Phe

Val Leu

195

Lys Lys 210

Thr His

Ser Val

Arg Thr

Pro Glu

275

Ala Lys 290

Val Ser

Ile Arg 85

Ile Ala 100

Ile Ala

Asn Tyr

Arg Asp

Gly Val

165

Glin Pro 180

Ser Phe

Ser Thr

Thr Cys

Phe Leu

245

Pro Glu 260

Val Lys

Thr Lys

Val Leu

Gly Asp

Glu Val

Asp Tyr

Trp Asn

Leu Tyr

135

Ile Ser

150

Glu Gly

Thr Asn

Glu Leu

Asn Leu

215

Pro Pro 230

Phe Pro

Val Thr

Phe Asn

Pro Arg

295

Thr Val 310

Asn Tyr

105

Ser Asn 120

Arg Leu

Thr Glu

Phe Asn

Gly Val

185

Leu His

200

Val Lys

Cys Pro

Pro Lys

Cys Val

265

Trp Tyr 280

Glu Glu

Leu His

Arg Gln 90

Lys Leu

Asn Leu

Phe Arg

Ile Tyr

155

Cys Tyr 170

Gly Tyr

Ala Pro

Asn Lys

Ala Pro

235

Pro Lys 250

Val Val

Val Asp

Gln Tyr

Gln Asp

315

Ile Ala

Pro Asp

Asp Ser

125

Lys Ser 140

Gln Ala

Phe Pro

Glin Pro

Ala Thr

205

Cys Val 220

Glu Leu

Asp Thr

Asp Val

Gly Val

285

Asn Ser 300

Trp Leu

Pro Gly 95

Asp Phe 110

Lys Val

Asn Leu

Gly Ser

Leu Gln

175

Tyr Arg 190

Val Cys

Asn Phe

Leu Gly

Leu Met

255

Ser His 270

Glu Val

Thr Tyr

Asn Gly

Gln

Thr

Gly

Lys

Thr 160

Ser

Val

Gly

Asp

Gly 240

Ile

Glu

His

Arg

Lys 320

- 654 044746

Glu Tyr Lys Cys Lys

325

Val Ser Asn Lys Ala

330

Leu Pro Ala Pro Ile

335

Lys Thr Ile Ser Lys

340

Ala Lys Gly Gln Pro

345

Arg Glu Pro Gln Val

350

Thr Leu Pro Pro Ser

355

Arg Asp Glu Leu Thr 360

Lys Asn Gln Val Ser

365

Thr Cys Leu Val Lys

370

Gly Phe Tyr Pro Ser

375

Asp Ile Ala Val Glu

380

Glu Ser Asn Gly Gln 385

Pro Glu Asn Asn Tyr 390

Lys Thr Thr Pro Pro 395

Leu Asp Ser Asp Gly

405

Ser Phe Phe Leu Tyr

410

Ser Lys Leu Thr Val

415

Lys Ser Arg Trp Gln

420

Gln Gly Asn Val Phe

425

Ser Cys Ser Val Met

430

Glu Ala Leu His Asn

435

His Tyr Thr Gln Lys 440

Ser Leu Ser Leu Ser

445

Glu

Tyr

Leu

Trp

Val 400

Asp

His

Pro

Gly Lys

450 <210> 832 <211> 1273 <212> PROTEIN <213> Artificial <220>

<223> Synthetic <400> 832

Met Phe Val Phe Leu

5 sequence

Val Leu Leu Pro Leu

Val Ser Ser Gln Cys

Asn Leu Thr Thr Arg 20

Thr Gln Leu Pro Pro

Ala Tyr Thr Asn Ser 30

Thr Arg Gly Val Tyr 35

Tyr Pro Asp Lys Val 40

Phe Arg Ser Ser Val 45

His Ser Thr Gln Asp 50

Leu Phe Leu Pro Phe 55

Phe Ser Asn Val Thr 60

Phe His Ala Ile His

Val Ser Gly Thr Asn

Gly Thr Lys Arg Phe

Val

Phe

Leu

Trp

Asp

- 655 044746

Asn

Lys

Lys

Lys

Tyr 145

Ser

Met

Val

Pro

Pro 225

Leu

Gly

Arg

Val

Ser 305

Pro Val Leu

Ser Asn Ile

100

Thr Gln Ser

115

Val Cys Glu 130

His Lys Asn

Ser Ala Asn

Asp Leu Glu

180

Phe Lys Asn

195

Ile Asn Leu 210

Leu Val Asp

Leu Ala Leu

Trp Thr Ala

260

Thr Phe Leu

275

Asp Cys Ala 290

Phe Thr Val

Pro Phe Asn 85

Ile Arg Gly

Leu Leu Ile

Phe Gln Phe

135

Asn Lys Ser

150

Asn Cys Thr 165

Gly Lys Gln

Ile Asp Gly

Val Arg Asp

215

Leu Pro Ile

230

His Arg Ser 245

Gly Ala Ala

Leu Lys Tyr

Leu Asp Pro

295

Glu Lys Gly 310

Asp Gly Val 90

Trp Ile Phe 105

Val Asn Asn 120

Cys Asn Asp

Trp Met Glu

Phe Glu Tyr

170

Gly Asn Phe

185

Tyr Phe Lys 200

Leu Pro Gln

Gly Ile Asn

Tyr Leu Thr

250

Ala Tyr Tyr

265

Asn Glu Asn 280

Leu Ser Glu

Ile Tyr Gln

Tyr Phe Ala

Gly Thr Thr

Ala Thr Asn 125

Pro Phe Leu 140

Ser Glu Phe 155

Val Ser Gln

Lys Asn Leu

Ile Tyr Ser

205

Gly Phe Ser

220

Ile Thr Arg 235

Pro Gly Asp

Val Gly Tyr

Gly Thr Ile

285

Thr Lys Cys

300

Thr Ser Asn 315

Ser Thr Glu

Leu Asp Ser 110

Val Val Ile

Gly Val Tyr

Arg Val Tyr

160

Pro Phe Leu

175

Arg Glu Phe 190

Lys His Thr

Ala Leu Glu

Phe Gln Thr

240

Ser Ser Ser

255

Leu Gln Pro 270

Thr Asp Ala

Thr Leu Lys

Phe Arg Val

320

- 656 044746

Gln

Pro

Trp

Tyr

Thr 385

Val

Lys

Val

Tyr

Glu 465

Asn

Phe

Leu

Lys

Gly 545

Pro

Pro Thr Glu

Phe Gly Glu

340

Asn Arg Lys

355

Asn Ser Ala 370

Lys Leu Asn

Ile Arg Gly

Ile Ala Asp

420

Ile Ala Trp

435

Asn Tyr Leu 450

Arg Asp Ile

Gly Val Glu

Gln Pro Thr

500

Ser Phe Glu

515

Ser Thr Asn 530

Leu Thr Gly

Phe Gln Gln

Ser Ile Val 325

Val Phe Asn

Arg Ile Ser

Ser Phe Ser

375

Asp Leu Cys

390

Asp Glu Val 405

Tyr Asn Tyr

Asn Ser Asn

Tyr Arg Leu

455

Ser Thr Glu

470

Gly Phe Asn 485

Asn Gly Val

Leu Leu His

Leu Val Lys

535

Thr Gly Val

550

Phe Gly Arg 565

Arg Phe Pro

330

Ala Thr Arg

345

Asn Cys Val 360

Thr Phe Lys

Phe Thr Asn

Arg Gln Ile

410

Lys Leu Pro

425

Asn Leu Asp 440

Phe Arg Lys

Ile Tyr Gln

Cys Tyr Phe

490

Gly Tyr Gln

505

Ala Pro Ala 520

Asn Lys Cys

Leu Thr Glu

Asp Ile Ala

570

Asn Ile Thr

Phe Ala Ser

Ala Asp Tyr

365

Cys Tyr Gly

380

Val Tyr Ala 395

Ala Pro Gly

Asp Asp Phe

Ser Lys Val

445

Ser Asn Leu

460

Ala Gly Ser 475

Pro Leu Gln

Pro Tyr Arg

Thr Val Cys

525

Val Asn Phe

540

Ser Asn Lys 555

Asp Thr Thr

Asn Leu Cys

335

Val Tyr Ala 350

Ser Val Leu

Val Ser Pro

Asp Ser Phe

400

Gln Thr Gly 415

Thr Gly Cys 430

Gly Gly Asn

Lys Pro Phe

Thr Pro Cys

480

Ser Tyr Gly

495

Val Val Val 510

Gly Pro Lys

Asn Phe Asn

Lys Phe Leu

560

Asp Ala Val

575

- 657 044746

Arg

Gly

Ala

His 625

Asn

Asn

Ser

Ser

Val 705

Ser

Asp

Leu

Gly

Val 785

Asn

Phe

Asp Pro

Gly Val

595

Val Leu 610

Ala Asp

Val Phe

Asn Ser

Tyr Gln

675

Gln Ser 690

Ala Tyr

Val Thr

Cys Thr

Leu Gln

755

Ile Ala

770

Lys Gln

Phe Ser

Ile Glu

Gln Thr 580

Ser Val

Tyr Gln

Gln Leu

Gln Thr

645

Tyr Glu 660

Thr Gln

Ile Ile

Ser Asn

Thr Glu

725

Met Tyr 740

Tyr Gly

Val Glu

Ile Tyr

Gln Ile

805

Asp Leu 820

Leu Glu

Ile Thr

Asp Val

615

Thr Pro 630

Arg Ala

Cys Asp

Thr Asn

Ala Tyr

695

Asn Ser 710

Ile Leu

Ile Cys

Ser Phe

Gln Asp

775

Lys Thr 790

Leu Pro

Leu Phe

Ile Leu

585

Pro Gly 600

Asn Cys

Thr Trp

Gly Cys

Ile Pro

65

Ser Pro 680

Thr Met

Ile Ala

Pro Val

Gly Asp

745

Cys Thr 760

Lys Asn

Pro Pro

Asp Pro

Asn Lys

825

Asp Ile

Thr Asn

Thr Glu

Arg Val

635

Leu Ile 650

Ile Gly

Arg Arg

Ser Leu

Ile Pro

715

SerMet

730

Ser Thr

Gln Leu

Thr Gln

Ile Lys

795

Ser Lys 810

Val Thr

Thr Pro

Thr Ser

605

Val Pro 620

Tyr Ser

Gly Ala

Ala Gly

Ala Arg

685

Gly Ala 700

Thr Asn

Thr Lys

Glu Cys

Asn Arg

765

Glu Val 780

Asp Phe

Pro Ser

Leu Ala

Cys Ser 590

Asn Gln

Val Ala

Thr Gly

Glu His

655

Ile Cys 670

Ser Val

Glu Asn

Phe Thr

Thr Ser

735

Ser Asn

750

Ala Leu

Phe Ala

Gly Gly

Lys Arg

815

Asp Ala 830

Phe

Val

Ile

Ser 640

Val

Ala

Ala

Ser

Ile 720

Val

Leu

Thr

Gln

Phe 800

Ser

Gly

- 658 044746

Phe Ile Lys

835

Gln Tyr Gly Asp Cys Leu Gly Asp Ile Ala Ala Arg Asp

840 845

Leu Ile Cys

850

Ala Gln Lys Phe Asn Gly Leu Thr Val Leu Pro Pro Leu

855 860

Leu Thr Asp 865

Glu Met Ile Ala Gln Tyr Thr Ser Ala Leu Leu Ala Gly

870 875 880

Thr Ile Thr

Ser Gly Trp Thr Phe Gly Ala Gly Ala Ala Leu Gln Ile

885 890 895

Pro Phe Ala

Met Gln Met Ala Tyr Arg Phe Asn Gly Ile Gly Val Thr

900 905 910

Gln Asn Val

915

Leu Tyr Glu Asn Gln Lys Leu Ile Ala Asn Gln Phe Asn

920 925

Ser Ala Ile

930

Gly Lys Ile Gln Asp Ser Leu Ser Ser Thr Ala Ser Ala

935 940

Leu Gly Lys 945

Leu Gln Asp Val Val Asn Gln Asn Ala Gln Ala Leu Asn

950 955 960

Thr Leu Val

Lys Gln Leu Ser Ser Asn Phe Gly Ala Ile Ser Ser Val

965 970 975

Leu Asn Asp

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

980 985 990

Ile Asp Arg

995

Leu Ile Thr Gly Arg Leu Gln Ser Leu Gln Thr Tyr Val

1000 1005

Thr Gln Gln

1010

Leu Ile Arg Ala Ala Glu Ile Arg Ala Ser Ala Asn Leu

1015 1020

Ala Ala Thr 1025

Lys Met Ser Glu Cys Val Leu Gly Gln Ser Lys Arg Val

1030 1035 1040

Asp Phe Cys

Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser Ala

1045 1050 1055

Pro His Gly

Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln Glu

1060 1065 1070

Lys Asn Phe

Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala His

- 659 044746

1075 10801085

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

1090 10951100

Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn Thr

1105 1110 11151120

Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn Thr

1125 11301135

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

1140 11451150

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

1155 11601165

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

1170 11751180

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

1185 1190 11951200

Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys Trp Pro Trp Tyr Ile

1205 12101215

Trp Leu Gly Phe Ile Ala Gly Leu Ile Ala Ile Val Met Val Thr Ile

1220 12251230

Met Leu Cys Cys Met Thr Ser Cys Cys Ser Cys Leu Lys Gly Cys Cys

1235 12401245

Ser Cys Gly Ser Cys Cys Lys Phe Asp Glu Asp Asp Ser Glu Pro Val

1250 12551260

Leu Lys Gly Val Lys Leu His Tyr Thr 12651270 <210> 833 <211> 1196 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 833

Val Asn Leu Thr Thr Arg Thr Gln Leu Pro Pro Ala Tyr Thr Asn Ser

5 10 15

- 660 044746

Phe

Leu

Trp

Asp 65

Glu

Ser

Ile

Tyr

Tyr 145

Leu

Phe

Thr

Glu

Thr 225

Ser

Pro

Thr Arg Gly Val Tyr Tyr Pro Asp Lys Val

25

His Ser Thr Gln Asp Leu Phe Leu Pro Phe

40

Phe His Ala Ile His Val Ser Gly Thr Asn 50 55

Asn Pro Val Leu Pro Phe Asn Asp Gly Val 70 75

Lys Ser Asn Ile Ile Arg Gly Trp Ile Phe

90

Phe Arg Ser Ser 30

Phe Ser Asn Val

Gly Thr Lys Arg 60

Tyr Phe Ala Ser

Gly Thr Thr Leu 95

Lys Thr Gln Ser Leu Leu Ile Val Asn Asn Ala Thr Asn Val

100 105 110

Lys Val Cys Glu Phe 115

Tyr His Lys Asn Asn 130

Ser Ser Ala Asn Asn

150

Met Asp Leu Glu Gly

165

Gln Phe Cys Asn Asp Pro Phe Leu Gly

120 125

Lys Ser Trp Met Glu Ser Glu Phe Arg 135 140

Cys Thr Phe Glu Tyr Val Ser Gln Pro

155

Lys Gln Gly Asn Phe Lys Asn Leu Arg

170 175

Val Phe Lys Asn Ile Asp Gly Tyr Phe Lys

180 185

Ile Tyr Ser Lys

190

Pro Ile Asn

195

Leu Val Arg Asp Leu Pro Gln Gly Phe

200 205

Ser Ala

Pro 210 Leu Val Asp Leu Pro 215 Ile Gly Ile Asn Ile 220 Leu Leu Ala Leu His 230 Arg Ser Tyr Leu Thr 235 Pro Gly Trp Thr Ala 245 Gly Ala Ala Ala Tyr 250 Tyr Val

Thr Arg Phe

Gly Asp Ser

Gly Tyr Leu

255

Val

Thr

Phe

Thr 80

Asp

Val

Val

Val

Phe 160

Glu

His

Leu

Gln

Ser 240

Gln

Asp

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

- 661 044746

260

265

270

Ala

Lys

Val 305

Cys

Ala

Leu

Pro

Phe 385

Gly

Cys

Asn

Phe

Cys 465

Gly

Val

Val Asp Cys

275

Ala Leu Asp

Pro Leu Ser 280

Glu Thr Lys

285

Cys Thr Leu

Ser Phe Thr 290

Gln Pro Thr

Pro Phe Gly

Trp Asn Arg

340

Tyr Asn Ser

355

Thr Lys Leu 370

Val Ile Arg

Lys Ile Ala

Val Ile Ala

420

Tyr Asn Tyr

435

Glu Arg Asp 450

Asn Gly Val

Phe Gln Pro

Leu Ser Phe

500

Val Glu Lys

295

Glu Ser Ile

310

Glu Val Phe 325

Lys Arg Ile

Ala Ser Phe

Asn Asp Leu

375

Gly Asp Glu

390

Asp Tyr Asn 405

Trp Asn Ser

Leu Tyr Arg

Ile Ser Thr

455

Glu Gly Phe

470

Thr Asn Gly 485

Glu Leu Leu

Gly Ile Tyr

Gln Thr Ser

300

Asn Phe Arg

Val Arg Phe

Asn Ala Thr

330

Ser Asn Cys

345

Ser Thr Phe 360

Cys Phe Thr

Val Arg Gln

Tyr Lys Leu

410

Asn Asn Leu

425

Leu Phe Arg 440

Glu Ile Tyr

Asn Cys Tyr

Val Gly Tyr

490

His Ala Pro

505

Pro Asn Ile 315

Thr Asn Leu

320

Arg Phe Ala

Val Ala Asp

Lys Cys Tyr

365

Asn Val Tyr

380

Ile Ala Pro 395

Pro Asp Asp

Asp Ser Lys

Lys Ser Asn

445

Gln Ala Gly

460

Phe Pro Leu 475

Gln Pro Tyr

Ala Thr Val

Ser Val Tyr

335

Tyr Ser Val 350

Gly Val Ser

Ala Asp Ser

Gly Gln Thr

400

Phe Thr Gly 415

Val Gly Gly 430

Leu Lys Pro

Ser Thr Pro

Gln Ser Tyr

480

Arg Val Val

495

Cys Gly Pro 510

- 662 044746

Lys

Asn

Leu 545

Val

Phe

Val

Ile

Ser 625

Val

Ala

Ala

Ser

Ile 705

Val

Leu

Thr

Lys Ser Thr

515

Gly Leu Thr 530

Pro Phe Gln

Arg Asp Pro

Gly Gly Val

580

Ala Val Leu

595

His Ala Asp 610

Asn Val Phe

Asn Asn Ser

Ser Tyr Gln

660

Ser Gln Ser

675

Val Ala Tyr 690

Ser Val Thr

Asp Cys Thr

Leu Leu Gln

740

Gly Ile Ala

755

Asn Leu Val

Gly Thr Gly

535

Gln Phe Gly

550

Gln Thr Leu 565

Ser Val Ile

Tyr Gln Asp

Gln Leu Thr

615

Gln Thr Arg

630

Tyr Glu Cys 645

Thr Gln Thr

Ile Ile Ala

Ser Asn Asn

695

Thr Glu Ile

710

Met Tyr Ile 725

Tyr Gly Ser

Val Glu Gln

Lys Asn Lys 520

Val Leu Thr

Arg Asp Ile

Glu Ile Leu

570

Thr Pro Gly

585

Val Asn Cys 600

Pro Thr Trp

Ala Gly Cys

Asp Ile Pro

650

Asn Ser Pro 6 65

Tyr Thr Met 680

Ser Ile Ala

Leu Pro Val

Cys Gly Asp

730

Phe Cys Thr 745

Asp Lys Asn 760

Cys Val Asn

525

Glu Ser Asn

540

Ala Asp Thr 555

Asp Ile Thr

Thr Asn Thr

Thr Glu Val

605

Arg Val Tyr

620

Leu Ile Gly 635

Ile Gly Ala

Arg Arg Ala

Ser Leu Gly

685

Ile Pro Thr

700

Ser Met Thr 715

Ser Thr Glu

Gln Leu Asn

Thr Gln Glu

765

Phe Asn Phe

Lys Lys Phe

Thr Asp Ala

560

Pro Cys Ser

575

Ser Asn Gln 590

Pro Val Ala

Ser Thr Gly

Ala Glu His

640

Gly Ile Cys

655

Arg Ser Val 670

Ala Glu Asn

Asn Phe Thr

Lys Thr Ser

720

Cys Ser Asn

735

Arg Ala Leu 750

Val Phe Ala

- 663 044746

Gln

Phe 785

Ser

Gly

Asp

Leu

Gly 865

Ile

Thr

Asn

Ala

Asn 945

Val

Gln

Val

Leu

Val Lys Gln Ile Tyr 770

Asn Phe Ser Gln Ile

790

Phe Ile Glu Asp Leu

805

Phe Ile Lys Gln Tyr 820

Leu Ile Cys Ala Gln

835

Leu Thr Asp Glu Met 850

Thr Ile Thr Ser Gly

870

Pro Phe Ala Met Gln

885

Gln Asn Val Leu Tyr 900

Ser Ala Ile Gly Lys

915

Leu Gly Lys Leu Gln 930

Thr Leu Val Lys Gln

950

Leu Asn Asp Ile Leu

965

Ile Asp Arg Leu Ile

980

Thr Gln Gln Leu Ile

995

Ala Ala Thr Lys Met 1010

Lys Thr Pro Pro Ile 775

Leu Pro Asp Pro Ser

795

Leu Phe Asn Lys Val

810

Gly Asp Cys Leu Gly

825

Lys Phe Asn Gly Leu

840

Ile Ala Gln Tyr Thr 855

Trp Thr Phe Gly Ala

875

Met Ala Tyr Arg Phe

890

Glu Asn Gln Lys Leu 905

Ile Gln Asp Ser Leu 920

Asp Val Val Asn Gln 935

Leu Ser Ser Asn Phe

955

Ser Arg Leu Asp Lys

970

Thr Gly Arg Leu Gln 985

Arg Ala Ala Glu Ile

1000

Ser Glu Cys Val Leu 1015

Lys Asp Phe Gly Gly 780

Lys Pro Ser Lys Arg

800

Thr Leu Ala Asp Ala

815

Asp Ile Ala Ala Arg 830

Thr Val Leu Pro Pro

845

Ser Ala Leu Leu Ala 860

Gly Ala Ala Leu Gln

880

Asn Gly Ile Gly Val

895

Ile Ala Asn Gln Phe

910

Ser Ser Thr Ala Ser

925

Asn Ala Gln Ala Leu 940

Gly Ala Ile Ser Ser

960

Val Glu Ala Glu Val

975

Ser Leu Gln Thr Tyr 990

Arg Ala Ser Ala Asn

1005

Gly Gln Ser Lys Arg 1020

- 664 044746

Val Asp Phe Cys Gly Lys Gly Tyr His Leu Met Ser Phe Pro Gln Ser

1025 1030 10351040

Ala Pro His Gly Val Val Phe Leu His Val Thr Tyr Val Pro Ala Gln

1045 10501055

Glu Lys Asn Phe Thr Thr Ala Pro Ala Ile Cys His Asp Gly Lys Ala

1060 10651070

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

1075 10801085

Val Thr Gln Arg Asn Phe Tyr Glu Pro Gln Ile Ile Thr Thr Asp Asn

1090 10951100

Thr Phe Val Ser Gly Asn Cys Asp Val Val Ile Gly Ile Val Asn Asn

1105 1110 11151120

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

1125 11301135

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

1140 11451150

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

1155 11601165

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

1170 11751180

Leu Gln Glu Leu Gly Lys Tyr Glu Gln Tyr Ile Lys 1185 11901195 <210> 834 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 834

Gly Gly Gly Gly Ser <210> 835 <211> 47 <212> PROTEIN

- 665 044746 <213> Artificial sequence <220>

<223> Synthetic <400> 835

Asp 1 Ile Ser Thr Glu 5 Ile Tyr Gln Ala Gly 10 Ser Thr Pro Cys Asn 15 Gly Val Glu Gly Phe 20 Asn Cys Tyr Phe Pro 25 Leu Gln Ser Tyr Gly 30 Phe Gln Pro Thr Asn 35 Gly Val Gly Tyr Gln 40 Pro Tyr Arg Val Val 45 Val Leu

<210> 836 <211> 21 <212> PROTEIN <213> Artificial sequence <220>

< 223> Synthetic < 400> 836

Cys Val Ile Ala Trp Asn Ser Asn Asn Leu Asp Ser Lys Val Gly Gly

5 10 15

Asn Tyr Asn Tyr Leu < 210> 837 < 211> 8 < 212> PROTEIN < 213> Artificial sequence <220>

< 223> Synthetic < 400> 837

Asp Ile Ser Thr Glu Ile Tyr Gln

5 < 210> 838 < 211> 34 < 212> PROTEIN < 213> Artificial sequence < 220>

< 223> Synthetic < 400> 838

Cys Asn Gly Val Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr

5 10 15

- 666 044746

Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln

Pro Tyr Arg Val Val

25 30

Leu > 839 > 44 > PROTEIN > Artificial sequence >

> Synthetic > 839

Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly 5 1015

Glu Gly Phe Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln 20 2530

Thr Asn Gly Val Gly Tyr Gln Pro Tyr Arg Val

3540 > 840 > 16 > PROTEIN > Artificial sequence >

> Synthetic > 840

Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe 5 10 15 > 841 > 25 > PROTEIN > Artificial sequence >

> Synthetic > 841

Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln 5 10 15

Tyr Arg Val Val Val Leu Ser Phe

25

- 667 044746 <210> 842 <211> 10 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 842

Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn

5 10 <210> 843 <211> 20 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 843

Asp Ile Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly

5 10 15

Val Glu Gly Phe 20 <210> 844 <211> 23 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 844

Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly Tyr Gln

5 10 15

Pro Tyr Arg Val 20

Val Val Leu <210> 845 <211> 23 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 845

Phe Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr

5 10 15

- 668 044746

Gly Lys Ile Ala Asp Tyr Asn <210> 846 <211> 34 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 846

Tyr Arg Leu Phe Arg Lys Ser Asn Leu Lys Pro Phe Glu Arg Asp 1 5 10 15

Ile

Ser Thr Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val

25 30

Glu

Gly Phe <210> 847 <211> 26 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 847

Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr Asn Gly Val Gly 1 5 10 15

Tyr

Gln Pro Tyr Arg Val Val Val Leu Ser Phe

25 <210> 848 <211> 24 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 848

Val Ile Arg Gly Asp Glu Val Arg Gln Ile Ala Pro Gly Gln Thr 1 5 10 15

Gly

Lys Ile Ala Asp Tyr Asn Tyr Lys 20 <210> 849

- 669 044746 <211> 43 <212> PROTEIN <213> Artificial sequence <220>

<223> Synthetic <400> 849

Glu Ile Tyr Gln Ala Gly Ser Thr Pro Cys Asn Gly Val Glu Gly Phe

5 1015

Asn Cys Tyr Phe Pro Leu Gln Ser Tyr Gly Phe Gln Pro Thr AsnGly

2530

Val Gly Tyr Gln Pro Tyr Arg Val Val Val Leu

3540 <210> 850 <211> 14 <212> PROTEIN <213> Artificial sequence <220>

< 223 > Synthetic < 400 > 850

Tyr Ala Trp Asn Arg Lys Arg Ile Ser Asn Cys Val Ala Asp

5 10

Claims (24)

1. An isolated antibody or antigen-binding fragment thereof that binds the SARS-CoV-2 spike protein containing the amino acid sequence set forth in SEQ ID NO: 832, wherein said isolated antibody or antigen-binding fragment comprises a heavy chain variable region (HCVR) containing the amino acid sequence , presented in SEQ ID NO: 202, and a light chain variable region (LCVR) containing the amino acid sequence presented in SEQ ID NO: 210. 2. An isolated antibody or an antigen-binding fragment thereof according to claim 1, which contains: (a) an immunoglobulin constant region; (b) IgG1 constant region; or (c) the human IgG1 constant region. 3. An isolated antibody or antigen-binding fragment thereof according to claim 1 or 2, which contains a heavy chain containing the amino acid sequence presented in SEQ ID NO: 216. 4. An isolated antibody or antigen-binding fragment thereof according to any one of claims 1 to 3, which contains a light chain containing the amino acid sequence presented in SEQ ID NO: 218. 5. An isolated antibody or antigen-binding fragment thereof according to any one of claims 1-4, where said antibody or antigen-binding fragment: (a) is multispecific; and/or (b) is a recombinant antibody or antigen binding fragment. 6. Pharmaceutical composition containing: i) an isolated antibody or an antigen-binding fragment thereof according to any one of claims 1 to 5; and ii) a pharmaceutically acceptable carrier or diluent. 7. A polynucleotide encoding a heavy chain variable region (HCVR) of an antibody or an antigen binding fragment thereof that binds the SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, wherein said HCVR includes the amino acid sequence set forth in SEQ ID NO: 202. 8. Polynucleotide according to claim 7, where said polynucleotide contains a nucleic acid sequence - 670 044746 HCVR acid shown in SEQ ID NO: 201. 9. The polynucleotide according to claim 7, wherein said antibody further comprises an immunoglobulin constant region. 10. The polynucleotide according to claim 9, wherein said immunoglobulin constant region is an IgG1 constant region. 11. The polynucleotide according to claim 7, wherein said antibody comprises the heavy chain amino acid sequence set forth in SEQ ID NO: 216. 12. The polynucleotide of claim 7, wherein said polynucleotide comprises the heavy chain nucleic acid sequence set forth in SEQ ID NO: 215. 13. The polynucleotide according to claim 7, wherein said polynucleotide is an RNA polynucleotide. 14. A vector containing a polynucleotide according to claim 7. 15. The vector of claim 14, wherein said vector is a lentiviral vector or an adeno-associated virus vector. 16. Lipid nanoparticle containing the polynucleotide according to claim 7. 17. A polynucleotide encoding a light chain variable region (LCVR) of an antibody or antigen binding fragment thereof that binds the SARS-CoV-2 spike protein comprising the amino acid sequence set forth in SEQ ID NO: 832, wherein said LCVR includes the amino acid sequence set forth in SEQ ID NO: 210. 18. The polynucleotide of claim 17, wherein said polynucleotide comprises the LCVR nucleic acid sequence set forth in SEQ ID NO: 209. 19. The polynucleotide of claim 17, wherein said antibody comprises the light chain amino acid sequence set forth in SEQ ID NO: 218. 20. The polynucleotide of claim 19, wherein said polynucleotide comprises the light chain nucleic acid sequence set forth in SEQ ID NO: 217. 21. The polynucleotide according to claim 17, wherein said polynucleotide is an RNA polynucleotide. 22. A vector containing a polynucleotide according to claim 17. 23. The vector of claim 22, wherein said vector is a lentiviral vector or an adeno-associated virus vector. 24. Lipid nanoparticle containing the polynucleotide according to claim 17.