RU2834996C1 - Anti-cd19 antibodies and methods for use and production thereof - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: invention relates to biotechnology, specifically to anti-CD19 antibodies, and can be used in medicine for treating a malignant tumour expressing CD19. Disclosed is a scFv peptide having specificity of binding to human CD19, containing the amino acid sequence of the variable region of the heavy chain SEQ ID NO: 7 and the amino acid sequence of the light chain variable region SEQ ID NO: 19. Based on said scFv peptide, multispecific antibody-like proteins having binding specificity with CD19, αEGFR, αPD-L1, α4-1BB, αHER3 and αCD3a of a human, as well as multispecific monoclonal antibodies having binding specificity to human CD19, and antibody-drug conjugates.

EFFECT: invention enables to obtain humanized antibodies specific for human CD19, having high stability and a lower risk of immunogenicity compared to the mouse antibody BU12.

30 cl, 11 dwg, 6 tbl, 9 ex

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to the filing date of U.S. Provisional Application Serial No. 62/984,731, filed March 3, 2020, under 35 U.S.C. 119(e), the entire contents of which are incorporated herein by reference.

AREA OF TECHNOLOGY

The present invention generally relates to the field of biological therapeutic agents and, more particularly, relates to the production and use of multispecific antibodies.

LEVEL OF TECHNOLOGY

Lymphoma accounts for 4.3% of all malignancies diagnosed annually in the United States, with B-cell malignancies accounting for approximately 90% of all lymphoma diagnoses. CD19 is a B-cell-specific member of the immunoglobulin superfamily expressed by B cells at various stages of differentiation, from the onset of V(D)J rearrangement to B-cell maturation into plasma cells, at which point CD19 surface expression appears to be lost. While CD19 is widely used as a general B-cell marker, high CD19 expression occurs in many forms of leukemia and lymphoma with features of B-cell origin. CD19 has been the focus of immunotherapy development for more than 30 years. Pharmaceutical companies have shown keen interest in anti-CD19 strategies because they show promise for directly targeting B-cell malignancies that correspond to early stages of B-cell differentiation. Targeting CD19 has been recognized as an excellent immunotherapy strategy, particularly when antibody therapies targeting CD22, another common B-cell marker expressed by B-cell malignancies, have failed.

CD19 is an important cell surface marker on normal B cells and B-cell derived malignancies. As such, an antibody targeting CD19 is highly desirable for use as a therapeutic agent against malignancy. Literature data demonstrate that it is difficult to identify anti-CD19 antibodies that also cross-react with cynomolgus monkey CD19, a property that greatly facilitates therapeutic pharmacological and toxicological testing. The historical antibody BU12 has been shown to have high affinity for human CD19 and cross-reactivity with cynomolgus monkey CD19, however, this antibody was derived from a mouse hybridoma and does not contain a human framework sequence. Thus, a humanized version of BU12 is highly desirable for therapeutic use.

ESSENCE OF THE INVENTION

This application describes peptides, proteins, protein complexes, antibodies against CD19 and methods for their production and use.

In one aspect, the present application relates to peptides having binding specificity for human CD19. In one embodiment, the peptide has an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 91, or 93.

In one embodiment, the peptide is an scFv peptide. In one embodiment, the scFv peptide may have a binding affinity for human CD19 with a KD of no more than 1 nM, 2 nM, 3 nM, 5 nM, 10 nM, 15 nM, 20 nM, 30 nM, 40 nM, or 50 nM.

In one aspect, the present application relates to an antibody or antigen-binding fragment thereof having binding specificity for human CD19. In one embodiment, the isolated antibody or antigen-binding fragment comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 91, or 93. In one embodiment, the antibody comprises an isolated monoclonal antibody (mAb).

In one embodiment, the antibody is a bispecific antibody. In one embodiment, the antibody is a multispecific antibody. In one embodiment, the antibody is a trispecific antibody, a tetraspecific antibody, a pentaspecific antibody, or a hexaspecific antibody.

In one embodiment, the antibody comprises an scFv, wherein the scFv comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 91 or 93.

In one embodiment, the antibody comprises a Fab, wherein the Fab comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 91, or 93.

In one embodiment, the present application relates to a multispecific antibody-like protein. In one embodiment, the protein comprises a peptide having an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 91 or 93. In one embodiment, the multispecific antibody-like protein has an N-terminus and a C-terminus comprising in tandem from N-terminus to C-terminus a first binding domain (D1) at the N-terminus, a second binding domain (D2) comprising a portion of a light chain, an Fc region, a third binding domain (D3) and a fourth binding domain (D4) at the C-terminus. The light chain portion comprises a fifth binding domain (D5) covalently linked to the C-terminus, a sixth binding domain (D6) covalently linked to the N-terminus, or both, and each of D1, D2, D3, D4, D5, and D6 has binding specificity for a tumor antigen, an immune signaling antigen, or a combination thereof.

In one embodiment, the multispecific antibody-like protein is pentaspecific. In one embodiment, the antibody-like protein comprises binding domains comprising D1, D2, D3, D4, and D6.

In one embodiment, the multispecific antibody-like protein is hexaspecific.

In one embodiment, D1 comprises a peptide comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 97%, 98% or 99% sequence identity to SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 91 or 93.

In one embodiment, D1 comprises a peptide having an amino acid sequence that has 95% sequence identity to SEQ ID NO: 7 or 19.

In one embodiment, D2 comprises a peptide comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 91, or 93.

In one embodiment, D2 comprises a peptide comprising an amino acid sequence having 95% sequence identity to SEQ ID NO: 91 or 93.

In one embodiment, D6 comprises a peptide having an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 91, or 93.

In one embodiment, D6 comprises a peptide having an amino acid sequence that has 95% sequence identity to SEQ ID NO: 7 or 19.

In one embodiment, the present application relates to a multispecific monoclonal antibody comprising a multispecific antibody-like protein as claimed herein.

In one embodiment, the multispecific monoclonal antibody may have a binding affinity for human CD19 with a Kd of no more than 1 nM, 5 nM, 10 nM, 20 nM, 30 nM, 40 nM, or 50 nM.

In one embodiment, the antibody is a humanized antibody. In one embodiment, the multispecific monoclonal antibody is IgG.

In one embodiment, the present application relates to an isolated nucleic acid encoding an isolated mAb or antigen-binding fragment, an IgG1 heavy chain, a kappa light chain, a light chain variable region, or a heavy chain variable region, as described.

In one aspect, the present application relates to an isolated nucleic acid sequence encoding an amino acid sequence of a multispecific monoclonal antibody as described herein.

In one embodiment, the present application relates to an expression vector comprising an isolated nucleic acid as described.

In one embodiment, the present application relates to host cells comprising a nucleic acid as described. In one embodiment, the host cell is a prokaryotic cell or a eukaryotic cell.

In one aspect, the present application relates to methods for producing an antibody comprising culturing a host cell such that the antibody is produced.

In one aspect, the present application relates to immunoconjugates. In one embodiment, an immunoconjugate comprises an isolated mAb or antigen-binding fragment thereof and a drug unit, wherein the drug unit is linked to the isolated mAb or antigen-binding fragment via a linker and wherein the linker comprises a covalent bond selected from an ester bond, an ether bond, an amino bond, an amide bond, a disulfide bond, an imide bond, a sulfone bond, a phosphate bond, a phosphorus ester bond, a peptide bond, a hydrazone bond, or a combination thereof.

In one embodiment, the dosage unit comprises a cytotoxic agent, an immunoregulatory agent, an imaging agent, or a combination thereof. In one embodiment, the cytotoxic agent is selected from a growth inhibitory agent or a chemotherapeutic agent from the class of tubulin binders, DNA intercalators, DNA alkylators, enzyme inhibitors, immunomodulators, antimetabolites, radioactive isotopes, or a combination thereof. In one embodiment, the cytotoxic agent is selected from calicheamicin, camptothecin, ozagomicin, monomethyl auristatin E, emtansine, a derivative thereof, or a combination thereof.

In one embodiment, the immunoregulatory reagents activate or suppress immune cells, T cells, NK cells, B cells, macrophages, or dendritic cells. In one embodiment, the imaging agent may be a radionuclide, a fluorescent agent, quantum dots, or a combination thereof.

In one aspect, the present application relates to a pharmaceutical composition. In one embodiment, the pharmaceutical composition comprises an isolated mAb or antigen-binding fragment thereof and a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition may further comprise a chemotherapeutic agent, a growth inhibitory agent, a calicheamicin cytotoxic agent, an antimitotic agent, a toxin, a radioactive isotope, a therapeutic agent, or a combination thereof.

In one aspect, the present application relates to a pharmaceutical composition comprising an immune conjugate as described herein and a pharmaceutically acceptable carrier.

In one aspect, the present application relates to methods of treating an individual with a cancer. In one embodiment, the method comprises administering to the individual an effective amount of an isolated mAb or antigen-binding fragment thereof as described. In one embodiment, the method may further comprise concomitantly administering an effective amount of a therapeutic agent, wherein the therapeutic agent comprises an antibody, a chemotherapeutic agent, an enzyme, or a combination thereof. In one embodiment, the individual is a human.

In a further aspect, the present application relates to a solution comprising an effective concentration of a multispecific monoclonal antibody as described herein. In one embodiment, the solution is blood plasma of an individual.

BRIEF DESCRIPTION OF DRAWINGS

The above and other features of the present invention will become more apparent from the following description and the appended claims, taken together with the accompanying drawings. Understanding that these drawings reflect only a few embodiments of the description and, therefore, should not be considered limiting its scope, the invention will be described more specifically and in detail using the accompanying drawings, in which:

Figure 1 shows the increase in similarity scores to human sequences (Z-score) from the mouse sequence (gray line) to the humanized framework region (dark line) in the variable regions of humanized BU12: H4 (Vk for the kappa light chain in 1A , and VH for the heavy chain in 1B ) and H5 (Vk for the kappa light chain in 1C and VH for the heavy chain in 1D );

Figure 2 shows the sequence alignment of the variable regions (VL for the light chain at 2A and VH for the heavy chain at 2B ) of humanized mouse BU12 (H1-H6 and H7) and human antibody (21D4);

Figure 3 shows the thermal stability of DLS for SI-63C1 (BU12 chimeric), SI-63C2 (humanized BU12, H1) and SI-34C1 (human antibody, 21D4);

Figure 4 shows histograms depicting the cross-reactivity of the SI-63C2 antibody against CD20+ B cells ( 4A ) and CD20- lymphocytes ( 4B ) from humans, cynomolgus monkeys, and rhesus monkeys;

Figure 5 shows the dose-response curve for binding of SI-63C2 antibody to human ( 5A ) , cynomolgus monkey ( 5B ), and rhesus monkey ( 5C ) CD20+ lymphocytes compared to the parental control (SI-63C1) and mouse anti-human CD19 antibody controls (SJ25C, LT19, HIB19, and 4G7);

Figure 6 shows the analytical SEC profile of SI-63R1(H1), a protein A-purified recombinant anti-CD19-HIS scFv protein ( 6A ), and the DLS thermal stability of SI-63R1(H1) with an unfolding temperature of approximately 58.8°C ( 6B );

Figure 7 shows the analytical SEC profile of protein A purified recombinant anti-CD19 scFv-mono-Fc proteins (H1 to H6) with 90% protein of interest (POI);

Figure 8 shows a schematic diagram of the six binding domains (D1-D6) in hexa-GNC antibodies, which contain the core Fab (D2) and Fc regions and additional D1, D3, and D4 on the heavy chain (HC) and D5 and D6 on the light chain;

Figure 9 shows the expression of ExpiCHO and purification of three hexa-GNC antibodies: SI-77H3, SI-77H6 and SI-55H11 with their humanized domains against CD19, H4 at D1, H7 at D2 (Fab) and H4 at D6, respectively;

Figure 10 shows the dose-response curves for direct cellular cytotoxicity (ADCC) of the antibody (SI-38E17, SI-55H11, SI-77H3, and SI-77H6, respectively) against either human ( 10A ) or cynomolgus monkey ( 10B ) PBMCs; and

Figure 11 shows that the humanized CD19 binding domain of hexa-GNC antibodies such as SI-77H, SI-77H6, and SI-55H11 mediate the cytolysis of Raji lymphoma cells that express only CD19 but not other tumor antigens ( 11A ), with an effective dose-response curve comparable to SI-38E17, a human anti-CD19 antibody (21D4) ( 11B ).

DETAILED DESCRIPTION

In the following detailed description, reference is made to the accompanying drawings, which form a part hereof. In the drawings, like symbols generally designate like components unless the context otherwise indicates. It is intended that the illustrative embodiments described in the detailed description, in the drawings, and in the claims are not limiting. Other embodiments may be utilized and other changes may be made without departing from the spirit or scope of the claimed subject matter described herein. It will be readily understood that aspects of the present invention generally described in the present description and illustrated in the drawings may be arranged, replaced, combined, separated, and organized in a wide variety of different configurations, all of which are expressly contemplated within the scope of the present invention.

The present invention relates, inter alia, to isolated antibodies, methods for producing such antibodies, monoclonal and/or recombinant monospecific antibodies, multispecific antibodies, antibody-drug conjugates and/or immunoconjugates consisting of such antibodies or antigen-binding fragments, pharmaceutical compositions containing antibodies, monoclonal and/or recombinant monospecific antibodies, multispecific, antibody-drug conjugates and/or immunoconjugates, methods for producing antibodies and compositions, and methods for treating a cancerous tumor using the antibodies and compositions described herein. In particular, the present invention relates to isolated monoclonal antibodies (mAbs) or antigen-binding fragments thereof having binding specificity for human CD19 ( Table 1 ), wherein the isolated mAb or antigen-binding fragments comprise an amino acid sequence having identity to a sequence selected from SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 91 or 93.

The singular form "a" or "an" as used herein means "one or more" and includes the plural unless the context otherwise requires.

The terms "polypeptide", "peptide" and "protein" as used herein are interchangeable and mean a biomolecule consisting of amino acids linked by a peptide bond.

The term "antigen" refers to a structure or fragment thereof that can induce an immune response in an organism, particularly an animal, more particularly a mammal, including humans. The term includes immunogens and their regions responsible for antigenicity or antigenic determinants.

The terms "antigen or epitope binding portion or fragment", "variable region", "variable region sequence" or "binding domain" refer to fragments of an antibody that are capable of binding to an antigen (such as CD19 in this application). These fragments may be capable of the antigen binding function and additional functions of the intact antibody. Examples of binding fragments include, but are not limited to, a single-chain Fv fragment (scFv), consisting of the variable domain of the light chain (VL) and the variable domain of the heavy chain (VH) of one arm of an antibody joined into a single polypeptide chain by a synthetic linker, or a Fab fragment, which is a monovalent fragment consisting of the VL, the constant domain of the light chain (CL), VH and the constant domain of the heavy chain 1 (CH1). Fragments may be even smaller subfragments and may consist of domains as small as a single CDR domain, particularly the CDR3 region of the VL and/or VH domains (e.g., see Beiboer et al., J. Mol. Biol. 296:833-49 (2000)). Antibody fragments are prepared using conventional techniques known in the art. Antibody fragments can be screened for utility using the same techniques used for intact antibodies.

An "antigen- or epitope-binding portion or fragment,""variableregion,""variable region sequence," or "binding domain" can be obtained from an antibody of the present invention by a variety of methods known in the art. For example, purified monoclonal antibodies can be digested with an enzyme such as pepsin and subjected to gel filtration by HPLC. Papain digestion of antibodies produces two identical antigen-binding fragments called "Fab" fragments, each with a single antigen-binding site, and a residual "Fc" fragment, the name of which reflects its ability to crystallize readily. Treatment with pepsin produces an F(ab') ₂ fragment, which has two antigen-binding sites and is still capable of binding antigen. The appropriate fraction containing the Fab fragments can then be collected and concentrated by membrane filtration, etc. For further descriptions of the basic methods for isolating active antibody fragments, see, for example, Khaw, BA et al. J. Nucl. Med. 23:1011–1019 (1982); Rousseaux et al. Methods Enzymology, 121:663–69, Academic Press, 1986.

The term "antibody" is used in the broadest sense and in particular covers single monoclonal antibodies and/or recombinant antibodies (including agonist antibodies and antagonist antibodies), compositions of antibodies with polyepitopic specificity, as well as antibody fragments (e.g., Fab, F(ab') ₂ and Fv), so long as they exhibit the desired biological activity. In some embodiments, the antibody can be a monoclonal, polyclonal, chimeric, single-chain, multispecific or multieffective human or humanized antibody, as well as fragments thereof. Examples of active fragments of molecules that bind known antigens include Fab, F(ab') ₂ -, scFv and Fv fragments, including Fab immunoglobulin expression library products and epitope-binding fragments of any of the antibodies and fragments mentioned above.

The term "Fv" refers to the minimum fragment of an antibody that contains a complete antigen recognition region and an antigen binding region. This region consists of a dimer of one heavy-chain variable domain and one light-chain variable domain in tight noncovalent association. It is in this configuration that the three CDRs of each variable domain interact to define the antigen-binding site on the surface of the VH-VL dimer. Collectively, the six CDRs provide the specificity of the antibody for antigen binding. However, even a single variable domain (or half of an Fv, containing only the three antigen-specific CDRs) has the ability to recognize and bind antigen, albeit with lower affinity than the entire binding site.

In some embodiments, an antibody may include immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e., molecules that contain a binding site and that immunospecifically bind an antigen. A typical antibody is a heterotetrameric protein typically consisting of two heavy (H) chains and two light (L) chains. Each heavy chain contains a heavy chain variable domain (abbreviated as VH) and a heavy chain constant domain. Each light chain contains a light chain variable domain (abbreviated as VL) and a light chain constant domain. The light chains of antibodies (immunoglobulins) from any vertebrate species can be classified into one of two distinct types, called kappa and lambda, based on the amino acid sequences of their constant domains. The VH and VL regions can be further subdivided into domains of hypervariable complementarity-determining regions (CDRs) and more conserved regions called framework regions (FRs). Each variable domain (either VH or VL) typically consists of three CDRs and four FRs, arranged in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4, from N-terminus to C-terminus. Within the variable regions of the light and heavy chains are binding sites that interact with antigen.

Depending on the amino acid sequence of the constant domain of their heavy chains, immunoglobulins can be classified into different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and some of these can be further subdivided into subclasses (isotypes), such as IgG-1, IgG-2, IgG-3, and IgG-4; IgA-1 and IgA-2. The heavy chain constant domains that correspond to the different immunoglobulin classes are called alpha, delta, epsilon, gamma, and mu, respectively. The subunit structures and three-dimensional configurations of the different immunoglobulin classes are well known.

The term "monoclonal antibody" as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed to a single antigenic site. Moreover, in contrast to conventional (polyclonal) antibody preparations, which typically include different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. In addition to their specificity, monoclonal antibodies are advantageous in that they are synthesized by a hybridoma culture uncontaminated by other immunoglobulins. The modifier "monoclonal" indicates the characteristic of the antibody that it is obtained from a substantially homogeneous population of antibodies and is not to be construed as requiring the production of the antibody by any particular method. For example, monoclonal antibodies for use in accordance with the present invention can be produced by the hybridoma method first described by Kohler and Milstein, Nature, 256:495 (1975), or they can be produced by recombinant DNA techniques (see, e.g., U.S. Patent No. 4,816,567). "Recombinant" means that the antibodies are produced using recombinant nucleic acid techniques in exogenous host cells.

Monoclonal antibodies can be produced using a variety of methods, including, but not limited to, mouse hybridoma, phage display, recombinant DNA, molecular cloning of antibodies directly from primary B cells, and antibody detection methods (see Siegel. Transfus. Clin. Biol. 2002; Tiller. New Biotechnol. 2011; Seeber et al. PLOS One. 2014). Monoclonal antibodies may include "chimeric" antibodies (immunoglobulins) in which a portion of the heavy and/or light chain is identical to or homologous with corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical to or homologous with corresponding sequences in antibodies derived from another species or belonging to a different antibody class or subclass, as well as fragments of such antibodies, provided that they exhibit the desired biological activity (U.S. Pat. No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 [1984]).

The term "multispecific" antibody, as used herein, means an antibody that has at least two binding sites, each of which has affinity for an epitope of an antigen. The term "bispecific, trispecific, tetraspecific, pentaspecific or hexaspecific" antibody, as used herein, means an antibody that has two, three, four, five or six antigen-binding sites. For example, the antibodies described herein with five binding sites are pentaspecific, with six binding sites are hexaspecific.

The term "targeting, guidance and control (GNC) protein" refers to a multispecific protein capable of binding to at least one antigen of an effector cell (such as an immune cell) and at least one antigen of a target cell (such as a tumor cell, an immune cell or a microbial cell). The GNC protein may have an antibody core structure comprising a Fab region and an Fc region, with various binding domains linked to the antibody core, in which case the GNC protein is also referred to as a GNC antibody. The GNC protein may have an antibody-like structure in which the Fv fragment may be replaced by a non-antibody binding domain such as NKG2D, 4-1BBL (4-1BB receptor ligand), 4-1BBL trimer of 4-1BB, or a receptor.

The term "GNC antibody" refers to a GNC protein that has an antibody structure that is capable of binding to at least one effector cell (such as an immune cell) and at least one target cell (such as a tumor cell, an immune cell, or a microbial cell) simultaneously. The term "bi-GNC, tri-GNC, tetra-GNC, penta-GNC, or hexa-GNC antibody" as used herein denotes a GNC antibody that has two, three, four, five, or six antigen-binding sites, of which at least one antigen-binding site has binding affinity for an immune cell and at least one antigen-binding site has affinity for a tumor cell. In one embodiment, the GNC antibodies described herein have four to six binding sites (or binding domains) and are tetra-GNC, penta-GNC, and hexa-GNC antibodies, respectively. In some embodiments, the GNC antibodies include antibody binding domains (such as Fab and scFv) without the need for further protein modification in the Fc region. In one embodiment, the GNC antibodies further have the advantage of maintaining bivalence for each target antigen. In addition, in one embodiment, the GNC antibodies have the advantage of avidity effects that result in higher affinity for antigens and lower off-rates. This bivalence for each antigen is in contrast to many multispecific platforms that are monovalent for each target antigen and thus often lack the beneficial avidity effects that make antibody binding so strong.

The term "humanized antibody" refers to a type of modified antibody in which the CDRs are derived from a non-human donor immunoglobulin and the remaining immunoglobulin-derived portions of the molecule are derived from one (or more) human immunoglobulin(s). In addition, ancillary framework residues may be altered to maintain binding affinity. Methods for producing "humanized antibodies" are well known to those skilled in the art. (See, e.g., Queen et al., Proc. Natl Acad Sci USA, 86:10029-10032 (1989), Hodgson et al., Bio/Technology, 9:421 (1991)).

The terms "isolated" or "purified" refer to a biological molecule that is free of at least some of the components with which it is found in nature. Both "isolated" and "purified," when used to describe the various polypeptides described herein, mean a polypeptide that has been identified or separated and/or recovered from the cell or cell culture from which it is expressed. Typically, a purified polypeptide is obtained by at least one purification step. An "isolated" or "purified" antibody refers to an antibody that is substantially free of other antibodies that have different binding specificities.

The term "immunogenic" refers to substances that induce or enhance the production of antibodies, T cells, or other reactive immune cells directed against an immunogenic agent and contribute to an immune response in humans or animals. An immune response occurs when an individual produces sufficient antibodies, T cells, and other reactive immune cells against the administered immunogenic compositions of the present invention to mitigate or alleviate the disorder being treated. While an immunogenic response typically includes both cellular (T cell) and humoral (antibody) arms of the immune response, antibodies directed against therapeutic proteins (anti-drug antibodies, ADAs) can be of the IgM, IgG, IgE, and/or IgA isotypes.

The terms "specific binding", "specifically binds to", or "is specific for a particular antigen or epitope" mean that the binding is detectably distinct from non-specific interaction. Specific binding can be determined, for example, by determining the binding of a molecule in comparison to the binding of a control molecule, which is typically a molecule of similar structure that does not have binding activity. For example, specific binding can be determined by competition with a control molecule that is similar to the target.

Specific binding to a particular antigen or epitope can be demonstrated, for example, by an antibody having a KD for the antigen or epitope of at least about 10 ^-4 M, at least about 10 ^-5 M, at least about 10 ^-6 M, at least about 10 ^-7 M, at least about 10 ^-8 M, at least about 10 ^-9 M, alternatively at least about 10 ^-10 M, at least about 10 ^-11 M, at least about 10 ^-12 M or more, wherein the KD refers to the dissociation rate for a particular antibody-antigen interaction. Typically, an antibody that specifically binds an antigen has a KD that is 20, 50, 100, 500, 1000, 5000, 10000 or more times greater than the KD of a reference molecule for the antigen or epitope.

Also, specific binding to a particular antigen or epitope can be demonstrated, for example, by an antibody having a KA or Ka with respect to the antigen or epitope that is at least 20, 50, 100, 500, 1000, 5000, 10000 or more times greater than the KA or Ka with respect to that epitope relative to a control, where the KA or Ka refers to the rate of association for a particular antibody-antigen interaction.

The present invention may be better understood by reference to the following detailed description of specific embodiments and examples included therein. Although the present invention has been described with respect to specific details of certain embodiments thereof, it is intended that such details should not be construed as limitations on the scope of the invention.

EXAMPLES

Example 1 . Construction of humanized anti-CD19 sequences

All computational steps were performed using the Discovery Studio software package (Dassault Systemes). First, a structural model was generated using the mouse BU12 sequence (McDonagh et al., 2009). The antibody framework regions in the input sequence were identified and aligned to the antibody variable domain database using hidden Markov models (HMMs), and this alignment was used to construct and evaluate models using MODELLER software. CDR loop modeling was performed by structurally mapping the CDRL1, CDRL2, CDRL3, CDRH1, and CDRH2 regions to known canonical classes, and loop models were constructed similarly to the framework region.

Framework regions from the mouse antibody BU12 were aligned and compared to the most similar human germline sequence, and the CDR regions were copied into the human sequence except for important structural residues (Vernier residues [Almagro and Fransson, 2008]). Mutations predicted to stabilize the previously constructed structural model were evaluated computationally by 1000 steps of steepest descent with an RMS gradient tolerance of 3, followed by conjugate gradient minimization, and stabilizing mutations corresponding to common human residues were selected based on individual and combined -ΔΔG against the original model. Energy analysis of stabilizing mutations was performed in Discovery studio using the H1 sequence as a reference. Versions H2, H3 and H4 are mutational variants that had negative mutation energy values (ΔΔG were -0.8, -1.5 and -1.1 kcal, respectively) and were predicted to be more stable than version H1. The resulting humanized sequence (H1, SEQ ID NOs: 1 and 13 ) was tested for similarity to human sequences using the Abysis web server based on the method of Abhinandan and Martin (2007). Using H4 as an example for its light chain (Vk) and heavy chain (VH), as shown in Fig. 1A and 1B, the humanized sequences exhibited a higher similarity score to human sequences than the corresponding mouse (BU12) sequences ( SEQ ID NOs: 25 and 27 ).

In addition, a direct CDR grafting approach was used to generate humanized versions of H5. The reference framework of the antibody was mutated to the same human germline residues and the CDRs were directly grafted into the mutated framework to generate H5. Using the resulting humanized H5 sequence as the base sequence, an additional mutation was introduced into the H5 framework to improve the stability of the framework, resulting in a humanized sequence (H6). The humanized H5 sequence ( SEQ ID NOS: 9 and 21 ) was tested for similarity to human sequences using the Abysis web server based on the method of Abhinandan and Martin (2007). The humanized sequences showed a higher similarity score to human sequences than the mouse (BU12) sequence (SEQ ID NOS: 25 and 27) ( Fig. 1C and 1D ).

H1 is the first humanized version derived directly from the variable domains of the BU12 Fab sequence with the signature amino acid sequence LEIK at the C-terminus. As shown in Fig. 2 , the last three residues (EIK) are predominantly present in naturally occurring kappa variable chains and provide stability when specifically located in the Fab domain. In this context, having H4, which terminates in VTVL, in the Fab position may not be ideal for antibody stability. The H7 version is a modified H4 that is thought to enhance protein stability when located in the Fab domain context (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058631/). H7 was generated by reconstituting EIK and introducing a disulfide bridge between H7VL and H7VH via mutation of Q to C and G to C, respectively.

To compare and prioritize these engineered sequences, all humanized variable regions (H1, H2, H3, H4, H5, H6, and H7) were aligned with sequences from the human anti-CD19 antibody 21D4 (Rao-Naik et al., 2009) as shown in Fig. 2 . The percent identity to H1 is 98.1% VL and 99.1-100% VH for H2, H3, H4, and H7, 85% VL and 86% VH for H5 and H6, and 70% VL and 51% VH for 21D4. These data imply that there is structural universality in the primary sequences of the CD19 binding domain.

To predict the immunogenicity of humanized sequences directed against CD19, the MixMHC2pred algorithm (Gfeller Lab, https://github.com/GfellerLab/MixMHC2pred) was used to predict the degree of major histocompatibility complex-II (MHC-II) binding of peptides in mouse and humanized sequences (VH/VL). The algorithm identifies the number of "core" peptides in a given amino acid sequence that bind to MCHII with sufficient affinity to form a T-cell epitope. The higher the number of MHCII-binding peptides in a sequence, the more potential T-cell epitopes the sequence contains. A higher number of core peptides increases the probability of the presence of some peptides that are pro-immunogenic. Thus, reducing the number of core peptides in antibody variable regions may help to reduce ADA by eliminating potential T-cell epitopes.

The anti-CD19 variable sequences were run through the MixMHC2pred algorithm as scFv (VH-(G4S)4-VL). The algorithm includes a scoring option across multiple alleles. In this case, "each peptide is scored as its best percentile rank across all alleles." The scoring strategy allows exploration of the sequences to find the most potent ligands for any MHCII allele. For the sequence analysis of the antibody variable domains, core peptides were calculated based on the number of peptides in the sequence that could bind to any of the MHCII alleles with a score corresponding to the best 0.2% of interactions. As shown in Table 1 , most of the humanized sequences have lower scores than their murine parental sequences, indicating peptides with weaker MHCII binding and a lower risk of immunogenicity. In this case, the overall score of the central peptides in the variable regions predicted to bind strongly to MHCII decreased from 9 for the mouse sequences to 5 for the humanized sequences (H1 through H4, and H7, no change for H5 and H6). Similarity scores to human sequences for the light and heavy chains were calculated using the human Z-score similarity analysis algorithm (Abhinandan & Andrew, 2007). For the VH sequences, H1-H4 had similar similarity to the human sequence to 21D4, while H5 and H6 had higher similarity to the human sequence and H7 had lower similarity to the human sequence. For the VK sequences, all of H1-H7 had similar similarity to the human sequence, which was slightly lower than that of 21D4. Notably, all humanized sequences (H1-H7, VH, and Vk) had significantly higher similarity scores to human sequences than the parental mouse sequences ( Table 1 ). Considering both the similarity to human sequence and the MHC-II binding scores of the peptide, H1-H4 and H7 were candidates for the generation of humanized anti-CD19 antibodies.

Example 2 . Expression of humanized monoclonal antibodies against CD19

To characterize the humanized light chain CDRs and heavy chain CDRs and framework regions, DNA sequences encoding H1 and other peptides were synthesized as overlapping fragments and cloned into the linearized pTT5 vector (NE Builder) containing the human kappa C-terminal sequence, or CH1, and the human IgG Fc region, respectively, creating a mAb format ( SEQ ID NOS: 37 and 39 ). DNA sequences for the 21D4 and mouse (BU12) variable regions were also synthesized and cloned into the linearized pTT5 vector containing the human kappa C-terminal sequence, or CH1, and the IgG Fc region, respectively, creating a chimeric mAb format ( SEQ ID NOS: 33, 35, 83 , and 85 ). Plasmid DNA containing the antibody sequences was expressed using the ExpiCHO expression system (ThermoFisher). Three recombinant antibodies, SI-63C1 (with the parental anti-CD19 mouse variable region sequence BU12), SI-63C2 (with the humanized anti-CD19 variable region sequence H1, also known as SI-huCD19), and SI-34C1 (with the human anti-CD19 variable region sequence 21D4), were purified from the culture supernatant using a Protein A affinity chromatography column (mabSelect Resin, Ge healthcare) with PBS (5X Cv) for washing and then 20 mM glycine pH 3.5 for elution. The resulting proteins were neutralized with 100X Tris, pH 8.5, and dialyzed overnight into PDB buffer. To test stability and monodispersity, purified antibodies were concentrated to 1 mg/mL and injected onto an analytical HPLC column (Waters, Waters BEH200A 300 mm column). Purified anti-CD19 antibodies showed a sharp, monodisperse peak of the correct size with 1.8-2.5% aggregate ( Table 2 ).

Example 3 . Characteristics of SI-63C2

Purified SI-63C1, SI-63C2, and SI-34C1 antibodies were tested for their binding affinity using biolayer interferometry (ForteBio OctetRED 384). The antibodies were coupled to anti-human Fc biosensors and human CD19 protein (R&D Biosystems, Cat# 9269-CD-050) was used as the analyte in a 4-point 2-fold dilution series with an initial peak concentration of 200 nM. The results of Octet analysis showed that the binding affinity of SI-63C3 (also known as SI-huCD19) to human and cynomolgus monkey CD19 was 3.8 nM and 3.6 nM, which were comparable to the affinity of anti-human CD19 antibody (21D4) at 2.1 nM and 3.8 nM, respectively. Moreover, the variable region sequences of the humanized anti-CD19 antibody SI-63C2 not only retained the binding specificity to human and cynomolgus monkey CD19, but also demonstrated comparable binding affinity (KD) to SI-63C1 (with BU12 variable region sequences) and SI-34C1 (with 21D4 variable region sequences) ( Table 2 ).

To test the thermal stability of SI-63C2, dynamic light scattering was used by gradually increasing the temperature from 25°C to 75°C at 0.5°C/min, and the protein radius (1 mg/mL) was monitored using a Wyatt DynaPro Plate Reader III. As shown in Fig. 3 and Table 2 , the results showed that SI-63C2 and SI-63C1 exhibited similar unfolding temperature as determined by Tm DLS, which was higher than that of SI-34C1.

Example 4 . Binding specificity of SI-63C2

Non-human primates (NHPs) such as cynomolgus and rhesus macaques are currently needed to provide risk assessment data for antibody drug development due to their similarity to humans, predicted metabolic stability, and historically known toxicity profiles. To minimize the use of NHPs and to improve efficacy, a candidate antibody drug should have high target specificity and cross-reactivity. In this context, CD19 is a common B-cell marker and is expressed by most malignant B cells. CD19 has a broader coverage of B-cell development and differentiation than CD20, which is another common B-cell marker for human lymphocytes and NHPs such as cynomolgus and rhesus macaques. Among many mouse anti-human CD19 antibodies, BU12 can cross-react with cynomolgus macaque-derived B lymphocytes with lower binding affinity (Liu et al., 2016).

Flow cytometry was performed to determine whether humanization alters cross-reactivity. The SI-63C2 antibody was used to bind human, cynomolgus, and rhesus monkey-derived peripheral blood mononuclear cells, respectively. Lymphocytes were gated based on forward and side scatter and then on single cells based on the height-to-area ratio of the forward scatter signal. Viable CD20+ B cells and CD20- lymphocytes were gated based on membrane-permeant amine-reactive dye exclusion and the level of anti-CD20 antibody (clone 2H7, Biolegend) binding. Labeled antibody binding was defined as the geometric mean fluorescence intensity (gMFI) of the cell population for the fluorescence coupled emission channel. As shown in the histogram analysis in Fig. 4 , the SI-63C2 antibody binds to human, cynomolgus, and rhesus macaque CD20+ B cells ( 4A ), but not to their CD20− lymphocytes ( 4B ). When a panel of anti-CD19 antibodies (namely, SJ25C, LT19, HIB19, and 4G7) were used for comparison, only SI-63C2 and its parent antibody SI-63C1 showed significant binding affinity to human, cynomolgus, and rhesus macaque CD20+ B cells ( Fig. 5 ). These data confirmed that the binding specificity of SI-63C2 to human, cynomolgus, and rhesus macaque B cells was maintained, but its cross-reactivity to the cynomolgus protein, as determined by EC50, remained lower than its response to human CD19 ( Table 3 ).

Example 5 . His-tagged humanized anti-CD19 scFv proteins

To characterize the humanized anti-CD19 binding domain as an element of scFv, DNA sequences encoding humanized anti-CD19 variable regions (H1) were cloned into a His-tagged scFv expression vector containing GSHHHHHH residues at the C-terminus of the scFv (SEQ ID NO: 41). Using the ExpiCHO expression system, the humanized His-tagged anti-CD19 scFv protein was expressed, purified by protein L affinity chromatography, and named SI-63R1. Analytical SEC data showed that SI-63R1 comprised 70% of the protein of interest, and the unfolding temperature of 58.8°C was determined for SI-63R1 in the DLS thermal stability assay ( Fig. 6 ).

To evaluate the binding affinity of SI-63R1, Octet binding assay was used. SI-63R1 protein was covalently loaded onto AR2G sensors at a concentration of 10 μg/mL and subjected to binding with serial dilutions of His-tagged human CD19 (1:2.5 dilutions from the highest concentration of 200 nM). The result shows that SI-63R1 has binding affinity for human CD19 in the low nanomolar range ( Table 2 ).

Example 6 . Humanized anti-CD19 scFv mono-Fc fusion proteins

For further screening and comparison of all humanized peptides, DNA sequences encoding humanized CD19-binding variants (H1, H2, H3, H4, H5, and H6) were converted to scFv-mono-Fc format and cloned (Dimitrov et al. 2012) ( SEQ ID NOs: 55,57,59,61,63,65 ). Using the ExpiCHO expression system, each of the 6 humanized anti-CD19-mono-Fc scFv fusion proteins was expressed and purified by Protein A affinity chromatography and named SI-63SF1(H1), SI-63SF2(H2), SI-63SF4(H3), SI-63SF5(H4), SI-63SF6(H5), and SI-63SF7(H6). Following the expression and purification processes, all six proteins were characterized for their physical properties including yield (titer), purity (% HMW and aSEC), binding affinity (KD, Kon, and Kdis) to human CD19, and thermal stability. For the Octet assay, scFv-mono-Fc fusion proteins were loaded onto the AHC sensors at 10 μg/mL and subjected to binding to serial dilutions of His-tagged human CD19 (1:2.5 dilutions starting from the highest concentration of 200 nM) and final global fitting to a 1:1 binding model. For the DLS assay, the temperature was gradually increased from 25°C to 75°C at a rate of 0.5°C/min while the radius of the scFv-mono-Fc fusion proteins (at a dose of 1 mg/mL) was monitored using a Wyatt DynaPro Plate Reader III. The analytical profiles of SEC are shown in Fig. 7 and all measurement results are given in Table 4 .

The data showed that SI-63SF5 (H4) had the highest melting temperature (Tm) at DLS of 51.8°C ( Table 4 ). Due to its higher thermal stability, the humanized variable region against CD19 with H4 peptide was selected for further study on the GNC antibody platform.

Example 7 . Humanized scFv or Fab domain against CD19 in GNC antibodies

Targeting, guidance and control (GNC) antibodies refer to multispecific antibodies capable of binding to an antigen(s) expressed by at least one target cell (including, but not limited to, a tumor cell, an immune cell or a microbial cell) and an antigen expressed by at least one effector cell (such as an immune cell) (see Applicant's application WO/2019/005642, incorporated herein by reference in its entirety). A GNC antibody comprises an antibody structure of Fab and Fc regions with various additional binding domains linked to the core portion of the antibody, such as one or more single-chain fragment variable domains, also known as scFv. GNC antibodies are capable of targeting tumor antigens, binding to immune-activating receptors, and at least directing immune effector cell-mediated tumor killing. For example, tetraspecific GNC antibodies (tetra-GNC) have been shown to exhibit desirable complex effects with structural and functional diversity but relatively independent binding domains (see Applicant's application WO/2019/191120, incorporated herein by reference in its entirety). In this context, a humanized anti-CD19 variable domain can be added to any GNC antibody as either a Fab domain or an scFv domain.

To characterize the humanized CD19 binding domain in GNC antibodies, DNA sequences encoding H4 and H7 were prepared and cloned into the GNC antibody format at one of five scFv positions and a Fab position, respectively ( Figure 8 shows a schematic of the configuration). The FR1 region of the humanized VH domain (H4) in VH3-containing scFvs on the GNC light chain, such as SI-55H11, was optionally mutated with R19S (Kabat numbering). When VH3-containing scFvs are coupled to the GNC light chain, the V _H domain can bind to the protein A resin during purification, causing the formation of light chain monomers and dimers that contaminate the desired heavy chain-light chain heterotetramer. To rationally disrupt protein A binding to VH3 family members, a structure-based approach was used to interrupt surface binding. The crystal structure of 1DEE (Graille M. et al. Proc. Nat. Acad. Sci. 2000) demonstrated that residue R19 in VH3 (Kabat numbering) is in direct contact with two side chains of the D domain of protein A. In particular, the contact of Q32 and D36 could be eliminated to significantly weaken the interaction. Therefore, R19 was mutated to serine, which does not mediate these interactions due to its shorter side chain. Furthermore, S19 exists naturally in other members of the VH family, indicating that it may be less immunogenic than other substitutions. For hexa-GNC antibodies, which may contain up to two VH3 scFvs per chain, this mutation is particularly important to ensure efficient purification of the desired product.

Table 5 shows hexa-GNC antibodies having a humanized CD19-binding domain H4 in D1 SI-77H3 (SEQ ID NOs: 67 and 69), in D2 (Fab) SI-77H6 (SEQ ID NOs: 71, 73), and in D6 SI-55H11 (SEQ ID NOs: 75 and 77); and penta-GNC antibody having a humanized CD19-binding domain H4 in D6 SI-38P12 (SEQ ID NOs: 87 and 89). Expression vectors encoding these GNC antibodies were transfected and expressed in the ExpiCHO system and all GNC antibodies were purified by protein A affinity chromatography. The yield and purity results by titer and aSEC demonstrated that GNC antibodies with a humanized CD19 binding domain as either scFv or Fab could be expressed and purified ( Fig. 9 and Table 6 ).

The Octet binding assay was used to determine the binding affinity of hexa- and penta-GNC antibodies to human CD19. GNC antibodies were loaded onto the AHC sensors at 10 μg/mL and subjected to binding to serial dilutions of His-tagged human CD19 (1:2.5 dilutions starting with a highest concentration of 200 nM) or a single concentration of 100 nM His-tagged human CD19. The resulting global fit to the 1:1 binding model demonstrated that these GNC antibodies bind to CD19 with affinity in the low nanomolar range ( Table 6 ).

Example 8 Positional effect of humanized CD19-binding domain in GNC antibodies

Human and cynomolgus monkey peripheral blood mononuclear cells (PBMCs) were used to assess humanized CD19 binding domain–mediated antibody-dependent cellular cytotoxicity. T cell recruiters were added to human or cynomolgus monkey PBMCs and cultured for 5 days. After 5 days, the cultures were harvested and both viable and nonviable CD20+ B cells were counted by FACS. Both viable single B cells and total viable B cells (singlets, doublets, or other cells in a gate) were analyzed independently. Relative total cell numbers were quantified using additional control bead counts. In this trial, the hexa-GNC antibodies tested included SI-77H3 (H4 at D1), SI-77H6 (H7 at D2, i.e. Fab), SI-55H11 (H4 at D6), and the control was a tetra-GNC antibody, SI-38E17 (SEQ ID NOs: 79 and 81), which had the human CD19 binding domain (21D4) in the Fab region (D2) ( Table 5 ).

Single-cell analysis by FACS tends to overlook the effect of T cell recruiters on the formation of non-cytolytic complexes, most of which appear to fall outside the single-cell gate. In contrast, analysis that includes doublet cells captures more events, thereby providing a more comprehensive understanding of cell-cell interactions. Figure 10 shows the results of the gated ADCC assay on all viable B cells. The control antibody, SI-38E17, exhibited binding specificity for human CD19 but not cynomolgus CD19. In comparison, all three hexa-GNC antibodies exhibited a similar response to both human and cynomolgus PBMC. Surprisingly, SI-77H6 did not appear to mediate ADCC on either human or cynomolgus PBMC despite having binding affinity for humanized CD19 ( Table 6 ). As shown in Table 5 , in SI-77H6, the humanized CD19 binding domain is the Fab region of the core structure of the antibody, while in both SI-77H3 and SI-55H11, the humanized CD19 binding domain of the scFv is added to the core structure of the antibody. The hexa-GNC antibody has at least 6 binding specificities, thus it is able to bind at least two different cell types in vivo simultaneously, which is a situation different from the affinity assessment of individual binding domains. This observed position-effect correlation indicates that there are biologically evident results mediated by the position effect of the humanized CD19 Fab domain in the GNC antibody and that SI-77H6 may be unable to support proper formation of cytolytic immune synapses between activated T cells and target B cells. Since CD19 is expressed by both normal and neoplastic B cells, the positional effect may be useful in targeting each binding domain to benefit the treatment of different types of malignancy, i.e., solid tumors versus liquid tumors. For example, an SI-77H6-linked GNC antibody may still be useful for the treatment of solid tumors with higher efficacy but lower cytotoxicity against normal B cells. In another example, an SI-77H6-linked GNC antibody may be useful for engaging B cell helpers in cytolytic interactions with T cells directed at other tumor-associated antigens.

Example 9 . RTCC via hexa-GNC antibodies with a humanized CD19-binding domain

To demonstrate the cytotoxic effect of hexa-GNC antibodies having a humanized CD19-binding domain, a retargeting T-cell cytotoxicity (RTCC) assay was performed using Raji cells. Raji lymphoblast-like cell line was derived from Burkitt lymphoma. Since each of the three hexa-GNC antibodies can bind to multiple tumor antigens other than CD19, such as EGFR, HER3, and PD-L1 ( Table 5 ), Raji cells expressing mKate2 fluorescent protein were stained with labeled monoclonal antibodies against individual tumor antigens and analyzed by FACS. The histogram results confirmed that Raji cells expressed CD19 and that no expression of EGFR, HER3, or PD-L1 could be detected ( Fig. 11A ).

Raji cells expressing the fluorescent protein mKate2 were cocultured with human CD8 T cells at a ratio of 5 T cells per Raji cell for 81 h in the presence of T cell recruiter proteins at concentrations ranging from 10 nM to 1 fM in triplicate. The fluorescent signal of target cells was assessed as an indicator of specific cytolysis by quantitative microscopy, and the dose-response curves were modeled using 5-parameter asymmetric sigmoid nonlinear regression and least squares fitting method using Graphpad Prism 8. As shown in Fig. 11B , the humanized CD19-binding domain in each of SI-55H11 (EC50, 2 pM), SI-77H3 (EC50, 8 pM), and SI-77H6 (EC50, 30 pM) mediated potent tumor cell cytolysis, and the potency of SI-55H11 was similar to that of SI-38E17 (EC50, 2 pM), an anti-human CD19 antibody (21D4) ( Table 6 ). SI-77H6 demonstrated suboptimal cytolysis with reduced efficiency parallel to its effect of CD19 binding to normal B cells without inducing cytolysis. SI-77H3 was able to achieve complete tumor cell killing but with reduced EC50. Thus, using optimized configuration and processing conditions (such as ratio of activated T cells to target cells), the described humanized CD19 binding domain can demonstrate the same potency as the human CD19 binding domain in multispecific GNC antibodies with the additional feature of cross-reactivity to cynomolgus monkey CD19.

While the present invention has been described with respect to specific embodiments or examples, it may be understood that the embodiments are illustrative and that the scope of the invention is not limited. Alternative embodiments of the present invention may become apparent to those skilled in the art to which the present invention pertains. It is intended that such alternative embodiments be encompassed within the scope of the present invention. Accordingly, the scope of the present invention is defined by the appended claims and based on the above description. All references cited or referred to in this specification are incorporated herein by reference in their entirety.

Links:

1. Watkins MP, Bartlett NL. CD19-targeted immunotherapies for treatment of patients with non-Hodgkin B-cell lymphomas. Expert Opin Investig Drugs. 2018;27(7):601-611. doi:10.1080/13543784.2018.1492549.

2. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5058631/.)

3. McDonagh, Charlotte et. Al. CD19 Binding agents and Uses Thereof. US 20090136526 A1.

4. Rao-Naik et. al. CD19 Antibodies and their uses. US 20090142349 A1.

5. Dimitrov et al. 2012: https://www.frontiersin.org/articles/10.3389/fimmu.2017.01545/full.

6. (Graille M. et al. Proc. Nat. Acad. Sci. 2000.)

TABLES:

Table 1. Computational calculation of humanized variable domains for overall MHCII binding scores and human sequence similarity scores using MixMHC2pred and the Z-score analysis algorithm, respectively. Peptide name (VH/VL) Sequence type Central peptides (MHCII binding) Similarity score to human sequences (Vk)
(Z-score) Similarity to human sequences (VH) (Z-score) BU12 (VH/VL) Mice 9 -1.40 -1.94 H1VH-H1VL Humanized 5 -0.77 -0.03 H2VH-H2VL Humanized 5 -0.75 -0.03 H3VH-H3VL Humanized 5 -0.77 -0.03 H4VH-H4VL Humanized 5 -0.75 -0.03 H5VH-H5VL Humanized 9 -0.70 0.58 H6VH-H6VL Humanized 9 -0.70 0.57 H7VH-H7VL Humanized 6 -0.56 -0.55 21D4 Human 12 0.86 -0.06

Table 2. Purity, binding affinity and thermal stability of SI-63C1 (with murine BU12 parental sequences), SI-63C2 (with humanized anti-CD19 H1 variable sequences), SI-34C1 (with anti-human CD19 21D4 variable sequences) and SI-63R1 (humanized His-tagged anti-CD19 scFv protein). Sample ID Format αCD19 domain (VH/VL) Titer (mcg/ml) %
aSEC KD
(nM) Kon
(1/ms) Kdis
(1/s) DLS Tm
(°C) SI-63C1 mAb BU12 250 98% 3.06 6.81E+04 2.09E-04 75.09 SI-63C2 mAb H1 235 99% 3.77 6.08E+04 2,29E-04 75.02 SI-34C1 mAb 21D4 60 96.45% 1.56 6.44E+04 1.01E-04 69.07 SI-63R1 ScFv H1 120 70% 1.33 4.99E+04 9,15E-05 58.8

Table 3. Cross-reactivity of recombinant antibodies (SI-63C1 and SI-63C2) and mouse anti-human CD19 antibodies (SJ25C, LT19, HIB19 and 4G7) against human, cynomolgus and rhesus macaque CD20+ lymphocytes as determined by EC50. mAb against CD19
EC50 µg/ml) Human CD20+ CD20+ cynomolgus macaque CD20+ rhesus macaque SI-63C2-AF647 Humanized 0.03974 2,901 0.6665 SI-63C1-AF647 Mice 0.2314 0.9093 0.9907 SJ25C-BV421 Mice 0.2088 N/A N/A LT19-FITC Mice 0,008687 N/A N/A HIB19-APC Mice 0,05441 N/A N/A 4G7-FITC Mice 0.5492 N/A N/A

Table 4. Purity, binding affinity and thermal stability of the humanized scFv fusion proteins against CD19 mono-Fc, SI-63SF1 (H1), SI-63SF2 (H2), SI-63SF4(H3), SI-63SF5 (H4), SI-63SF6 (H5) and SI-63SF7 (H6). scFv-Fc
ID αCD19 domain
(VH/VL) Titer (mcg/ml) %
HMW %
aSEC KD (nM) Kon
(1/ms) Kdis
(1/s) DLS Tm
(°C) SI-63SF1 H1 130 20% 80% 6.89 4.41E+04 1,84E-03 46.9 SI-63SF2 H2 121 15% 85% 4.22 4.28E+04 1,81E-03 45.1 SI-63SF4 H3 174 12% 89% 4.18 4.56E+04 1,91E-03 51.2 SI-63SF5 H4 110 11% 88% 5.02 3.72E+04 1,87E-03 51.8 SI-63SF6 H5 101 8% 92% 5.68 5.97E+04 3.39E-04 49.8 SI-63SF7 H6 97 7% 91% 5.37 7.02E+04 3.77E-04 50.1

Table 5. Positions of the humanized CD19-binding domain and other antigen-binding domains in GNC antibodies. ID GNC Ab Multispecificity D1 D2
(Fab) D3 D4 D5 D6 SI-77H3 Hexa H4 αEGFR αPD-L1 α4-1BB αHER3 αCD3 SI-77H6 Hexa αHER3 H7 αPD-L1 α4-1BB αHER3 αCD3 SI-55H11 Hexa αEGFR αCD3 αPD-L1 α4-1BB αHER3 H4 SI-38P12 Penta αCD20 αCD3 αPD-L1 α4-1BB - H4 SI-38E17 Tetra αCD3 21D4 αPD-L1 α4-1BB - -

Table 6. Physical and functional characteristics of GNC antibodies containing humanized scFv domain or Fab region against CD19. ID GNC Ab Multi-specificity Position of αCD19 αCD19 domain (VH/VL) Titer (mcg/ml) aSEC %POI αCD19
KD (nM) EC50
(p.m.) SI-77H3 Hexa D1 H4 68.4 86.91 7.53 8.1 SI-77H6 Hexa D2 H4 58.6 78.51 5.25 30.2 SI-55H11 Hexa D6 H4 61.9 76.95 4.54 2.5 SI-38P12 Penta D6 H4 101.2 79.05 1.11 n/a SI-38E17 Tetra D2 21D4 61.1 80.54 1.48 2.1

SEQUENCE LIST:

Sample ID Annotation SEQ ID NO: Protein DNA H1VH Humanized heavy chain variable region 1 1 2 H2VH Humanized heavy chain variable region 2 3 4 H3VH Humanized heavy chain variable region 3 5 6 H4VH Humanized heavy chain variable region 4 7 8 H5VH Humanized heavy chain variable region 5 9 10 H6VH Humanized heavy chain variable region 6 11 12 H7VH Humanized heavy chain variable region 7 91 92 H1VL Humanized light chain variable region 1 13 14 H2VL Humanized light chain variable region 2 15 16 H3VL Humanized light chain variable region 3 17 18 H4VL Humanized light chain variable region 4 19 20 H5VL Humanized light chain variable region 5 21 22 H6VL Humanized light chain variable region 6 23 24 H7VL Humanized light chain variable region 7 93 94 BU12VH Mouse anti-CD19 heavy chain variable sequence 25 26 BU12VL Anti-mouse CD19 light chain variable sequence 27 28 21D4VH Human CD19 heavy chain variable sequence 29 30 21D4VL Anti-human CD19 light chain variable sequence 31 32 SI-63C1HC Heavy chain mAb version BU12 33 34 SI-63C1LC Light chain kappa mAb version BU12 35 36 SI-63C2HC mAb heavy chain humanized version 1 37 38 SI-63C2LC Light chain mAb humanized version 1 39 40 SI-63R1 His-tagged humanized ScFv version 1 41 42 SI-63SV1 ScFv humanized version 1 43 44 SI-63SV2 ScFv humanized version 2 45 46 SI-63SV3 ScFv humanized version 3 47 48 SI-63SV4 ScFv humanized version 4 49 50 SI-63SV5 ScFv humanized version 5 51 52 SI-63SV6 ScFv humanized version 6 53 54 SI-63SV7 ScFv humanized version 7 95 96 SI-63SF1 ScFv-mono-Fc humanized version 1 55 56 SI-63SF2 ScFv-mono-Fc humanized version 2 57 58 SI-63SF4 ScFv-mono-Fc humanized version 3 59 60 SI-63SF5 ScFv-mono-Fc humanized version 4 61 62 SI-63SF6 ScFv-mono-Fc humanized version 5 63 64 SI-63SF7 ScFv-mono-Fc humanized version 6 65 66 SI-77H3HC Hexa-GNC Heavy Chain 67 68 SI-77H3LC Hexa-GNC Light Chain 69 70 SI-77H6HC Hexa-GNC Heavy Chain 71 72 SI-77H6LC Hexa-GNC Light Chain 73 74 SI-55H11HC Hexa-GNC Heavy Chain 75 76 SI-55H11LC Hexa-GNC Light Chain 77 78 SI-38E17HC Tetra-GNC Heavy Chain 79 80 SI-38E17LC Tetra-GNC Light Chain 81 82 SI-34C1 Heavy chain mAb 21D4 83 84 SI-34C1 Light chain mAb 21D4 85 86 SI-38P12LC Penta-GNC Light Chain 87 88 SI-38P12HC Heavy Chain PentaGNC 89 90

>Sequence ID 1: Amino acid sequence of humanized version 1(H1VH)

QVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 2: Nucleotide sequence of humanized version 1(H1VH)

CAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACAAACGG TATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT

>Sequence ID 3: Amino acid sequence of humanized version 2(H2VH)

QVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 4: Nucleotide sequence of humanized version 2 (H2VH)

CAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACAAACGG TATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT

>Sequence ID 5: Amino acid sequence of humanized version 3(H3VH)

QVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 6: Nucleotide sequence of humanized version 3(H3VH)

CAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACAAACGG TATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT

>Sequence ID 7: Amino acid sequence of humanized version 4(H4VH)

QVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 8: Nucleotide sequence of humanized version 4(H4VH)

CAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACAAACGG TATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT

>Sequence ID 9: Amino acid sequence of humanized version 5(H5VH)

EVQLVESGGGLVQPGGSLRLSCVFSGFSLSTSGMGVGWVRQAPGKGLEWVGHIWWDDDKRYNPALKSRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 10: Nucleotide sequence of humanized version 5(H5VH)

GAGGTGCAACTTGTGGAAAGCGGCGGCGGGTTGGTGCAACCTGGCGGTTCACTTCGGCTCTCATGTGTGTTCAGTGGTTTTTCCCTTAGCACAAGCGGGATGGGTGTCGGGTGGGTCCGCCAAGCGCCTGGCAAAGGTCTGGAATGGGTTGGTCACATTTGGTGGGATGATGACAAAAGG TATAATCCCGCGCTGAAATCTAGATTTACTATTAGTCGGGATACGAGTAAGAACACGGTGTATCTGCAAATGAACAGTCTCAGGGCAGAGGATACAGCGGTATATTATTGTGCTCGAATGGAGCTGTGGTCTTACTATTTTGATTACTGGGGCCAGGGCACGTTGGTAACGGTCTCGAGT

>Sequence ID 11: Amino acid sequence of humanized version 6(H6VH)

EVQLVESGGGLVQPGGSLRLSCSFSGFSLSTSGMGVGWVRQAPGKGLEWVGHIWWDDDKRYNPALKSRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 12: Nucleotide sequence of humanized version 6 (H6VH)

GAGGTGCAACTTGTGGAAAGCGGCGGCGGGTTGGTGCAACCTGGCGGTTCACTTCGGCTCTCATGTAGCTTCAGTGGTTTTTCCCTTAGCACAAGCGGGATGGGTGTCGGGTGGGTCCGCCAAGCGCCTGGCAAAGGTCTGGAATGGGTTGGTCACATTTGGTGGGATGATGACAAAAGG TATAATCCCGCGCTGAAATCTAGATTTACTATTAGTCGGGATACGAGTAAGAACACGGTGTATCTGCAAATGAACAGTCTCAGGGCAGAGGATACAGCGGTATATTATTGTGCTCGAATGGAGCTGTGGTCTTACTATTTTGATTACTGGGGCCAGGGCACGTTGGTAACGGTCTCGAGT

>Sequence ID 13: Amino acid sequence of humanized version 1(H1VL)

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLEIK

>Sequence ID 14: Nucleotide sequence of humanized version 1 (H1VL)

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTG GCTTCCGGCGTACCTAGCCGCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAATTGGAGATAAAG

>Sequence ID 15: Amino acid sequence of humanized version 2 (H2VL)

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKITIL

>Sequence ID 16: Nucleotide sequence of humanized version 2 (H2VL)

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTG GCTTCCGGCGTACCTAGCCGCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAAATTACGATACTG

>Sequence ID 17: Amino acid sequence of humanized version 3 (H3VL)

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLTVL

>Sequence ID 18: Nucleotide sequence of humanized version 3 (H3VL)

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTG GCTTCCGGCGTACCTAGCCGCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAACTTACGGTACTG

>Sequence ID 19: Amino acid sequence of humanized version 4 (H4VL)

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVL

>Sequence ID 20: Nucleotide sequence of humanized version 4 (H4VL)

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTG GCTTCCGGCGTACCTAGCCGCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAAGTTACGGTACTG

>Sequence ID 21: Amino acid sequence of humanized version 5 (H5VL)

EIVMTQSPSTLSASVGDRVIITCSASSSVSYMHWYQQKPGKAPKLLIYDTSKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCFQGSVYPFTFGQGTKLTVL

>Sequence ID 22: Nucleotide sequence of humanized version 5 (H5VL)

GAAATAGTGATGACGCAGTCACCTAGCACCCTTAGTGCTTCTGTAGGAGACAGGGTTATAATTACCTGCAGTGCTAGTTCCTCAGTGTCATACATGCACTGGTATCAGCAGAAACCGGGAAAAGCTCCAAAGCTGCTTATATACGACACGTCCAAATTG GCATCAGGTGTCCCCAGTCGATTTAGTGGCTCTGGCTCAGGGGCTGAATTTACGCTCACAATCTCCAGCCTCCAACCAGATGACTTCGCCACATACTACTGTTTTCAGGGCTCAGTGTATCCGTTTACTTTCGGCCAGGGGACAAAGTTGACTGTACTT

>Sequence ID 23: Amino acid sequence of humanized version 6 (H6VL)

EIVMTQSPSTLSASVGDRVIITCSASSSVSYMHWYQQKPGKAPKLLIYDTSKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCFQGSVYPFTFGQGTKLTVL

>Sequence ID 24: Nucleotide sequence of humanized version 6 (H6VL)

GAAATAGTGATGACGCAGTCACCTAGCACCCTTAGTGCTTCTGTAGGAGACAGGGTTATAATTACCTGCAGTGCTAGTTCCTCAGTGTCATACATGCACTGGTATCAGCAGAAACCGGGAAAAGCTCCAAAGCTGCTTATATACGACACGTCCAAATTG GCATCAGGTGTCCCCAGTCGATTTAGTGGCTCTGGCTCAGGGGCTGAATTTACGCTCACAATCTCCAGCCTCCAACCAGATGACTTCGCCACATACTACTGTTTTCAGGGCTCAGTGTATCCGTTTACTTTCGGCCAGGGGACAAAGTTGACTGTACTT

>Sequence ID 25: BU12 VH: Mouse anti-CD19 VH amino acid sequence

QVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGVGWIRQPSGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSSNQVFLKIASVDTADTAAYYCARMELWSYYFDYWGQGTTLTVSS

>Sequence ID 26: BU12 VH: Mouse anti-CD19 VH nucleotide sequence

CAGGTGACCCTGAAAGAAAGCGGCCCGGGCATTCTGCAGCCGAGCCAGACCCTGAGCCTGACCTGCAGCTTTAGCGGCTTTAGCCTGAGCACCAGCGGCATGGGCGTGGGCTGGATTCGCCAGCCGAGCGGCAAAGGCCTGGAATGGCTGGCGCATATTTGGTGGGATGATGATAAACGC TATAACCCGGCGCTGAAAAGCCGCCTGACCATTAGCAAAGATACCAGCAGCAACCAGGTGTTTCTGAAAATTGCGAGCGTGGATACCGCGGATACCGCGGCGTATTATTGCGCGCATGGAACTGTGGAGCTATTATTTTGATTATTGGGGCCAGGGCACCACCCTGACCGTGAGCAGC

>Sequence ID 27: BU12 VL: Mouse anti-CD19 VL amino acid sequence

ENVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSSTSPKLWIYDTSKLASGVPGRFSGSGSGNSHFLTISSMEAEDVATYYCFQGSVYPFTFGSGTKLEIK

>Sequence ID 28: BU12 VL: Mouse VL anti-CD19 nucleotide sequence

GAAAACGTGCTGACCCAGAGCCCGGGCGATTATGAGCGCGAGCCCGGGCGAAAAAGTGACCATGACCTGCAGCGCGAGCAGCAGCGTGAGCTATATGCATTGGTATCAGCAGAAAAGCAGCACCAGCCCGAAACTGTGGATTTATGATACCAGCAAACTG GCGAGCGGCGTGCCGGGCCGCTTTAGCGGCAGCGGCAGCGGCAACAGCCATTTTCTGACCATTAGCAGCATGGAAGCGGAAGATGTGGCGACCTATTATTGCTTTCAGGGCAGCGTGTATCCGTTTACCTTTGGCAGCGGCACCAAACTGGAAATTAAA

>Sequence ID 29: Amino acid sequence of VH of human antibody 21D4

EVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWIGWVRQAPGKGLEWMGIIYPDDSDTRYSPSFQGQVTISADKSIRTAYLQWSSLKASDTAMYYCARHVTMIWGVIIDFWGQGTLVTVSS

>Sequence ID 30: Nucleotide sequence of VH of human antibody 21D4

GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTGAAGAAACCAGGAGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGCTTTAGCAGTTCATGGATCGGCTGGGTGCGCCAGGCACCTGGGAAAGGCCTGGAATGGATGGGGATCATCTATCCTGATGACTCTGATACCAGATACA GTCCATCCTTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGGACTGCCTACCTGCAGTGGAGTAGCCTGAAGGCCTCGGACACCGCTATGTATTACTGTGCGAGACATGTTACTATGATTTGGGGAGTTATTATTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA

>Sequence ID 31: Amino acid sequence of VL human antibody 21D4

AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPFTFGPGTKVDIK

>Sequence ID 32: Nucleotide sequence of VL human antibody 21D4

GCCATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGCAGTGCTTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCTCCTAAGCTCCTGATCTATGATGCCTCCAGTT TGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGTTTAATAGTTACCCATTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAA

>Sequence ID 33: Amino acid sequence of the heavy chain of SI-63C1

QVTLKESGPGILQPSQTLSLTCSFSGFSLSTSGMGVGWIRQPSGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSSNQVFLKIASVDTADTAAYYCARMELWSYYFDYWGQ GTTLTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCD KTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

>Sequence ID 34: Nucleotide sequence of the heavy chain of SI-63C1

CAGGTGACCCTGAAAGAAAGCGGCCCGGGCATTCTGCAGCCGAGCCAGACCCTGAGCCTGACCTGCAGCTTTAGCGGCTTTAGCCTGAGCACCAGCGGCATGGGCGTGGGCTGGATTCGCCAGCCGAGCGGCAAAGGCCTGGAATGGCTGGCGCATATTTGGTGGGAT GATGATAAACGCTATAACCCGGCGCTGAAAAGCCGCCTGACCATTAGCAAAGATACCAGCAGCAACCAGGTGTTTCTGAAAATTGCGAGCGTGGATACCGCGGATACCGCGGCGTATTATTGCGCGCGCATGGAACTGTGGAGCTATTATTTTGATTATTGGGGCCAG GGCACCACCCTGACCGTGAGCAGCGCTAGCACCAAGGGCCCATCTGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCTGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCTGAACCTGTGACAGTGTCCTGGAACTCAGGAGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACA AAACTCACACATGCCCACCGTGCCCAGCACCTCCTGTAGCAGGACCGTCAGTCTTCCTTCTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACG TGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACGCCAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAAC CATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTA CAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCCGGGCAAA

>Sequence ID 35: Amino acid sequence of the light chain of SI-63C1

ENVLTQSPAIMSASPGEKVTMTCSASSSVSYMHWYQQKSSTSPKLWIYDTSKLASGVPGRFSGSGSGNSHFLTISSMEAEDVATYYCFQGSVYPFTFGSGTKLEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>Sequence ID 36: Nucleotide sequence of the light chain of SI-63C1

GAAAACGTGCTGACCCAGAGCCCGGGCGATTATGAGCGCGAGCCCGGGCGAAAAAGTGACCATGACCTGCAGCGCGAGCAGCAGCGTGAGCTATATGCATTGGTATCAGCAGAAAAGCAGCACCAGCCCGAAACTGTGGATTTATGATACCAGCAAACTG GCGAGCGGCGTGCCGGGCCGCTTTAGCGGCAGCGGCAGCGGCAACAGCCATTTTCTGACCATTAGCAGCATGGAAGCGGAAGATGTGGCGACCTATTATTGCTTTCAGGGCAGCGTGTATCCGTTTACCTTTGGCAGCGGCACCAAACTGGAAATTAAAC GTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGA GAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT

>Sequence ID 37: Amino acid sequence of the heavy chain of SI-63C2

QVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQ GTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCD KTHTCPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEK TISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

>Sequence ID 38: Nucleotide sequence of the heavy chain of SI-63C2

CAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGAC GACGACAAACGGTATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAG GGGACTCTCGTCACGGTGTCCTCTGCTAGCACCAAGGGCCCATCTGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCTGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCTGAACCTGTGACAGTGTCCTGGAACTCAGGAGCCCTGACCAGC GGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGACA AAACTCACACATGCCCACCGTGCCCAGCACCTCCTGTAGCAGGACCGTCAGTCTTCCTTCTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACG TGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACGCCAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAAC CATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTA CAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCCGGGCAAA

>Sequence ID 39: Amino acid sequence of the light chain of SI-63C2

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLEIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>Sequence ID 40: Nucleotide sequence of the light chain of SI-63C2

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTG GCTTCCGGCGTACCTAGCCGCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAATTGGAGATAAAGC GTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGGA GAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT

>Sequence ID 41: Amino acid sequence of SI-63R1 (H1 ScFv-His) ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLEIKGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGSHHHHHH

>Sequence ID 42: Nucleotide sequence SI-63R1 (H1 ScFv-His)

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCAGTGGTTC CGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAATTGGAGATAAAGGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCACAGG TCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACAAACGGTATAATCCTGCCTTG AAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGTGGATCCCATCATCACCATCACCATTGA

>Sequence ID 43: Amino acid sequence of SI-63SV1

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLEIKGGGGSGGGGSGGGGSGG GGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 44: Nucleic acid sequence SI-63SV1

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCA GTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAATTGGAGATAAAGGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGT GGAGGATCACAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACA AACGGTATAATCCTGCCTTGAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT

>Sequence ID 45: Amino acid sequence of SI-63SV2

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKITILGGGGSGGGGSGGGGSGG GGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 46: Nucleic acid sequence SI-63SV2

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCA GTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAAATTACGATACTGGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGT GGAGGATCACAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACA AACGGTATAATCCTGCCTTGAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT

>Sequence ID 47: Amino acid sequence of SI-63SV3

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLTVLGGGGSGGGGSGGGGSGG GGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 48: Nucleic acid sequence SI-63SV3

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCA GTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAATTGACGGTACTGGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGT GGAGGATCACAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACA AACGGTATAATCCTGCCTTGAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT

>Sequence ID 49: Amino acid sequence of SI-63SV4

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGG GGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 50: Nucleic acid sequence SI-63SV4

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCA GTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAAGTTACGGTACTGGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGT GGAGGATCACAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACA AACGGTATAATCCTGCCTTGAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT

>Sequence ID 51: Amino acid sequence of SI-63SV5

EIVMTQSPSTLSASVGDRVIITCSASSSVSYMHWYQQKPGKAPKLLIYDTSKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCFQGSVYPFTFGQGTKLTVLGGGGSGGGGSGGGGSGG GGSEVQLVESGGGLVQPGGSLRLSCVFSGFSLSTSGMGVGWVRQAPGKGLEWVGHIWWDDDKRYNPALKSRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 52: Nucleic acid sequence of SI-63SV5

GAAATAGTGATGACGCAGTCACCTAGCACCCTTAGTGCTTCTGTAGGAGACAGGGTTATAATTACCTGCAGTGCTAGTTCCTCAGTGTCATACATGCACTGGTATCAGCAGAAACCGGGAAAAGCTCCAAAGCTGCTTATATACGACACGTCCAAATTGGCATCAGGTGTCCCCAGTCGATTTA GTGGCTCTGGCTCAGGGGCTGAATTTACGCTCACAATCTCCAGCCTCCAACCAGATGACTTCGCCACATACTACTGTTTTCAGGGCTCAGTGTATCCGTTTACTTTCGGCCAGGGGACAAAGTTGACTGTACTTGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGT GGAGGATCAGAGGTGCAACTTGTGGAAAGCGGCGGCGGGTTGGTGCAACCTGGCGGTTCACTTCGGCTCTCATGTGTGTTCAGTGGTTTTTCCCTTAGCACAAGCGGATGGGTGTCGGGTGGGTCCGCCAAGCGCCTGGCAAAGGTCTGGAATGGGTTGGTCACATTTGGTGGGATGATGACA AAAGGTATAATCCCGCGCTGAAATCTAGATTTACTATTAGTCGGGATACGAGTAAGAACACGGTGTATCTGCAAATGAACAGTCTCAGGGCAGAGGATACAGCGGTATATTATTGTGCTCGAATGGAGCTGTGGTCTTACTATTTTGATTACTGGGGCCAGGGCACGTTGGTAACGGTCTCGAGT

>Sequence ID 53: Amino acid sequence of SI-63SV6

EIVMTQSPSTLSASVGDRVIITCSASSSVSYMHWYQQKPGKAPKLLIYDTSKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCFQGSVYPFTFGQGTKLTVLGGGGSGGGGSGGGGSGG GGSEVQLVESGGGLVQPGGSLRLSCSFSGFSLSTSGMGVGWVRQAPGKGLEWVGHIWWDDDKRYNPALKSRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 54: Nucleic acid sequence SI-63SV6

GAAATAGTGATGACGCAGTCACCTAGCACCCTTAGTGCTTCTGTAGGAGACAGGGTTATAATTACCTGCAGTGCTAGTTCCTCAGTGTCATACATGCACTGGTATCAGCAGAAACCGGGAAAAGCTCCAAAGCTGCTTATATACGACACGTCCAAATTGGCATCAGGTGTCCCCAGTCGATTTA GTGGCTCTGGCTCAGGGGCTGAATTTACGCTCACAATCTCCAGCCTCCAACCAGATGACTTCGCCACATACTACTGTTTTCAGGGCTCAGTGTATCCGTTTACTTTCGGCCAGGGGACAAAGTTGACTGTACTTGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGT GGAGGATCAGAGGTGCAACTTGGAAAGCGGCGGCGGTTGGTGCAACCTGGCGGTTCACTTCGGCTCTCATGTAGCTTCAGTGGTTTTTCCCTTAGCACAAGCGGATGGGTGTCGGGTGGGTCCGCCAAGCGCCTGGCAAAGGTCTGGAATGGGTTGGTCACATTTGGTGGGATGATGACA AAAGGTATAATCCCGCGCTGAAATCTAGATTTACTATTAGTCGGGATACGAGTAAGAACACGGTGTATCTGCAAATGAACAGTCTCAGGGCAGAGGATACAGCGGTATATTATTGTGCTCGAATGGAGCTGTGGTCTTACTATTTTGATTACTGGGGCCAGGGCACGTTGGTAACGGTCTCGAGT

>Sequence ID 55: Amino acid sequence of SI-63SF1 (H1 ScFv-mono-Fc)

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLEIKGGGGSGGGGSGGGGSGG GGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS GGSSGSGSGSTGLVPRGSTSSSGTGTSAGTPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLRCHVKGFYPSDIAVEWESNGQPENNYKTTKPVLDSDGSFFLYSTLTVDKSRWQQGNVFSCSVLHEALHNHYTQKSLSLSPGKGSGLNDIFEAQKIEWHE

>Sequence ID 56: Nucleotide sequence of SI-63SF1 (H1 ScFv-mono-Fc)

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCA GTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAATTGGAGATAAAGGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGT GGAGGATCACAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACA AACGGTATAATCCTGCCTTGAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT

GGGGGATCCTCTGGAAGTGGCTCCGGCAGCACTGGGCTCGTACCAAGGGGGTCCACATCCAGTAGCGGTACTGGCACATCCGCGGGAACCCCCGTCGCTGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCAC GAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACGCTAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGA AAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGAGATGCCACGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGAAGCCCGTGCTGGA CTCCGACGGCTCCTTCTTCCTCTACAGCACCCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTCCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCCGGGCAAAGGTTCAGGCCTGAACGATATTTTTTGAAGCGCAGAAAATTGAATGGCATGAA

>Sequence ID 57: Amino acid sequence of SI-63SF2 (H2 ScFv-mono-Fc)

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKITILGGGGSGGGGSGGGGSGGGGS QVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGSSGSG SGSTGLVPRGSTSSSGTGTSAGTPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSRDELTKNQVSLRCHVKGFYPSDIAVEWESNGQPENNYKTTKPVLDSDGSFFLYSTLTVDKSRWQQGNVFSCSVLHEALHNHYTQKSLSLSPGKGSGLNDIFEAQKIEWHE

>Sequence ID 58: Nucleotide sequence of SI-63SF2 (H2 ScFv-mono-Fc)

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCA GTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAAATTACGATACTGGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGT GGAGGATCACAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACA AACGGTATAATCCTGCCTTGAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT GGGGGATCCTCTGGAAGTGGCTCCGGCAGCACTGGGCTCGTACCAAGGGGGTCCACATCCAGTAGCGGTACTGGCACATCCGCGGGAACCCCCGTCGCTGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCAC GAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACGCTAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGA AAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGAGATGCCACGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGAAGCCCGTGCTGGA CTCCGACGGCTCCTTCTTCCTCTACAGCACCCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTCCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCCGGGCAAAGGTTCAGGCCTGAACGATATTTTTTGAAGCGCAGAAAATTGAATGGCATGAA

>Sequence ID 59: Amino acid sequence of SI-63SF4 (H3 ScFv-mono-Fc)

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKLTVLGGGGSGGGGSGGGGSGGGGS QVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGSSGSG SGSTGLVPRGSTSSSGTGTSAGTPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSRDELTKNQVSLRCHVKGFYPSDIAVEWESNGQPENNYKTTKPVLDSDGSFFLYSTLTVDKSRWQQGNVFSCSVLHEALHNHYTQKSLSLSPGKGSGLNDIFEAQKIEWHE

>Sequence ID 60: Nucleotide sequence SI-63SF4 (H3 ScFv-mono-Fc)

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCA GTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAACTTACGGTACTGGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGT GGAGGATCACAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACA AACGGTATAATCCTGCCTTGAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT

GGGGGATCCTCTGGAAGTGGCTCCGGCAGCACTGGGCTCGTACCAAGGGGGTCCACATCCAGTAGCGGTACTGGCACATCCGCGGGAACCCCCGTCGCTGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCAC GAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACGCTAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGA AAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGAGATGCCACGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGAAGCCCGTGCTGGA CTCCGACGGCTCCTTCTTCCTCTACAGCACCCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTCCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCCGGGCAAAGGTTCAGGCCTGAACGATATTTTTTGAAGCGCAGAAAATTGAATGGCATGAA

>Sequence ID 61: Amino acid sequence of SI-63SF5 (H4 ScFv-mono-Fc)

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGS QVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGSSGSG SGSTGLVPRGSTSSSGTGTSAGTPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSRDELTKNQVSLRCHVKGFYPSDIAVEWESNGQPENNYKTTKPVLDSDGSFFLYSTLTVDKSRWQQGNVFSCSVLHEALHNHYTQKSLSLSPGKGSGLNDIFEAQKIEWHE

>Sequence ID 62: Nucleotide sequence of SI-63SF5 (H4 ScFv-mono-Fc)

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCA GTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAAGTTACGGTACTGGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGT GGAGGATCACAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACA AACGGTATAATCCTGCCTTGAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGT

GGGGGATCCTCTGGAAGTGGCTCCGGCAGCACTGGGCTCGTACCAAGGGGGTCCACATCCAGTAGCGGTACTGGCACATCCGCGGGAACCCCCGTCGCTGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCAC GAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACGCTAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGA AAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGAGATGCCACGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGAAGCCCGTGCTGGA CTCCGACGGCTCCTTCTTCCTCTACAGCACCCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTCCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCCGGGCAAAGGTTCAGGCCTGAACGATATTTTTTGAAGCGCAGAAAATTGAATGGCATGAA

>Sequence ID 63: Amino acid sequence of SI-63SF6 (H5 ScFv-mono-Fc)

EIVMTQSPSTLSASVGDRVIITCSASSSVSYMHWYQQKPGKAPKLLIYDTSKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCFQGSVYPFTFGQGTKLTVLGGGGSGGGGSGGGGSGGGGS EVQLVESGGGLVQPGGSLRLSCVFSGFSLSTSGMGVGWVRQAPGKGLEWVGHIWWDDDKRYNPALKSRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGSSGSGS GSTGLVPRGSTSSSGTGTSAGTPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSRDELTKNQVSLRCHVKGFYPSDIAVEWESNGQPENNYKTTKPVLDSDGSFFLYSTLTVDKSRWQQGNVFSCSVLHEALHNHYTQKSLSLSPGKGSGLNDIFEAQKIEWHE

>Sequence ID 64: Nucleotide sequence of SI-63SF6 (H5 ScFv-mono-Fc)

GAAATAGTGATGACGCAGTCACCTAGCACCCTTAGTGCTTCTGTAGGAGACAGGGTTATAATTACCTGCAGTGCTAGTTCCTCAGTGTCATACATGCACTGGTATCAGCAGAAACCGGGAAAAGCTCCAAAGCTGCTTATATACGACACGTCCAAATTGGCATCAGGTGTCCCCAGTCGATTTAGTGGC TCTGGCTCAGGGGCTGAATTTACGCTCACAATCTCCAGCCTCCAACCAGATGACTTCGCCACATACTACTGTTTTCAGGGCTCAGTGTATCCGTTTACTTTCGGCCAGGGGACAAAGTTGACTGTACTTGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCAG AGGTGCAACTTGTGGAAAGCGGCGGCGGGTTGGTGCAACCTGGCGGTTCACTTCGGCTCTCATGTGTGTTCAGTGGTTTTTCCCTTAGCACAAGCGGGATGGGTGTCGGGTGGGTCCGCCAAGCGCCTGGCAAAGGTCTGGAATGGGTTGGTCACATTTGGTGGGATGATGACAAAAGGTATAATCCGGC GCTGAAATCTAGATTTACTATTAGTCGGGATACGAGTAAGAACACGGTGTATCTGCAAATGAACAGTCTCAGGGCAGAGGATACAGCGGTATATTATTGTGCTCGAATGGAGCTGTGGTCTTACTATTTTGATTACTGGGGCCAGGGCACGTTGGTAACGGTCTCGAGTGGATCCTCTGGAAGTGGCTCC GGCAGCACTGGGCTCGTACCAAGGGGGTCCACATCCAGTAGCGGTACTGGCACATCCGCGGGAACCCCCGTCGCTGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAG TTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACGCTAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCA AAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGAGATGCCACGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGAAGCCCGTGCTGGACTCCGA CGGCTCCTTCTTCCTCTACAGCACCCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTCCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCCGGGCAAAGGTTCAGGCCTGAACGATATTTTTTGAAGCGCAGAAAATTGAATGGCATGAA

>Sequence ID 65: Amino acid sequence of SI-63SF7 (H6 ScFv-mono-Fc)

EIVMTQSPSTLSASVGDRVIITCSASSSVSYMHWYQQKPGKAPKLLIYDTSKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCFQGSVYPFTFGQGTKLTVLGGGGSGGGGSGGGGSGGGGS EVQLVESGGGLVQPGGSLRLSCSFSGFSLSTSGMGVGWVRQAPGKGLEWVGHIWWDDDKRYNPALKSRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGSSGSGS GSTGLVPRGSTSSSGTGTSAGTPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTIS KAKGQPREPQVYTLPPSRDELTKNQVSLRCHVKGFYPSDIAVEWESNGQPENNYKTTKPVLDSDGSFFLYSTLTVDKSRWQQGNVFSCSVLHEALHNHYTQKSLSLSPGKGSGLNDIFEAQKIEWHE

>Sequence ID 66: Nucleotide sequence of SI-63SF7 (H6 ScFv-mono-Fc)

GAAATAGTGATGACGCAGTCACCTAGCACCCTTAGTGCTTCTGTAGGAGACAGGGTTATAATTACCTGCAGTGCTAGTTCCTCAGTGTCATACATGCACTGGTATCAGCAGAAACCGGGAAAAGCTCCAAAGCTGCTTATATACGACACGTCCAAATTGGCATCAGGTGTCCCCAGTCGATTTAGTGGC TCTGGCTCAGGGGCTGAATTTACGCTCACAATCTCCAGCCTCCAACCAGATGACTTCGCCACATACTACTGTTTTCAGGGCTCAGTGTATCCGTTTACTTTCGGCCAGGGGACAAAGTTGACTGTACTTGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCAG AGGTGCAACTTGTGGAAAGCGGCGGCGGGTTGGTGCAACCTGGCGGTTCACTTCGGCTCTCATGTAGCTTCAGTGGTTTTTCCCTTAGCACAAGCGGGATGGGTGTCGGGTGGGTCCGCCAAGCGCCTGGCAAAGGTCTGGAATGGGTTGGTCACATTTGGTGGGATGATGACAAAAGGTATAATCCG GCTGAAATCTAGATTTACTATTAGTCGGGATACGAGTAAGAACACGGTGTATCTGCAAATGAACAGTCTCAGGGCAGAGGATACAGCGGTATATTATTGTGCTCGAATGGAGCTGTGGTCTTACTATTTTGATTACTGGGGCCAGGGCACGTTGGTAACGGTCTCGAGTGGATCCTCTGGAAGTGGCTCC GGCAGCACTGGGCTCGTACCAAGGGGGTCCACATCCAGTAGCGGTACTGGCACATCCGCGGGAACCCCCGTCGCTGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAG TTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACGCTAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCA AAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGAGATGCCACGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGAAGCCCGTGCTGGACTCCGA CGGCTCCTTCTTCCTCTACAGCACCCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGCTCCATGAGGCTCTGCACAACCACTACACACAGAAGAGCCTCTCCCTGTCTCCGGGCAAAGGTTCAGGCCTGAACGATATTTTTTGAAGCGCAGAAAATTGAATGGCATGAA

>Sequence ID 67: Amino acid sequence of the heavy chain of SI-77H3

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSG FSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGFSLTNYGVHWIRQAPGKCLEWLG VIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKGLEWIA CIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSR FSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYY CARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKVEIK

>Sequence ID 68: Nucleic acid sequence of the heavy chain of SI-77H3

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTA TGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAAGTGACCGTCCTAGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCACAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGCCTCACCTGTGCCTTCAGTGGTTTT TCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACAAACGGTATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCTCGGATGGAACTCTGGT CTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCACAAGTACAGTTGCAGCAATCCGGTCCCGGTCTCGTCAAACCGAGTGAGACGCTTAGTATAACGTGTACTGTTTCAGGCTTTAGCCTTACGAACTATGGAGTTCACTGGATTCGGCAGGCACCCGGCAAATGTTTGGAATGGCTGGGTGTT ATTTGGTCAGGTGGAAATACAGACTATAACACCCCCTTTACAAGTCGGTTCACAATTACGAAAGATAATTCCAAAAATCAAGTTTATTTCAAGTTGAGATCCGTCCGCGCGGACGACACTGCGATCTACTATTGTGCGAGGGCACTGACCTACTACGATTACGAATTTGCGTATTGGGGGCAAGGGACTCTTGTAACAGTCTCCAGTGCTAGCACCAAGGGCCCATCGG TCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAAC GTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGT ACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCC CGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGG CTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCGAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGTACA GCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCTTCAGTAGCGGGTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCATGC ATTGCTGCTGGTAGTGCTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGATCGGCGTTTTCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTGTCGAGCGGTGGAGGCGGATCTG GCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGTTC AGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGTT TTCGGCGGAGGGACCAAGGTGGAGATCAAAGGCGGTGGAGGGTCCGGCGGTGGTGGCTCCGGACGGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGA GACTCTCCTGTACTGCCTCTGGATTCACCATCAGTAGCTACCACATGCAGTGGGTCCGCCAGGCTCCAGGAAGGGGCTGGAGTACATCGGAACCATTAGTAGTGGTGGTAATGTATACTACGCAAGCTCCGCTAGAGGCAGATTCACCATCTCCAGACCCTCGTCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGT GCGAGAGACTCTGGTTATAGTGATCCTATGTGGGGCCAGGGAACCCTGGTCACCGTCTCTTCAGGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCAGACGTTGTGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACCTGTCAGGCCAGTCAGAACATTAGGACTTACTTATCCTGGT ATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAGCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGCCTGGCGATGCTGCAACTTACTATTGTCAGTCTACCTATCTTGGTACTGATTATGTTGGCGGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAATGA

>Sequence ID 69: Amino acid sequence of the light chain of SI-77H3

EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGQGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLSLSCAASGFTISTNAMSWVRQAPGKGLEWVGVITG RDITYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSGGGGSGGGGSEIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGCGTKLTVLR TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRF SGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS

>Sequence ID 70: Nucleotide sequence of the light chain of SI-77H3

GAAATCGTTATGACGCAGAGTCCCTCCACGCTCTCCGCTAGTGTCGGGGATCGCGTCATTATCACATGCCAGGCCTCCGAGTCAATCAGCAGCTGGCTTGCATGGTATCAACAGAAGCCGGGAAAAGCTCCTAAATTG CTGATCTATGAAGCGTCAAAATTGGCGTCTGGTGTCCCATCTAGGTTCTCCGGCTCTGGGTCTGGTGCGGAATTTACTTTGACAATCTCCAGTCTTCAACCAGACGATTTCGCTACCTACTACTGCCAAGGGTATTTCT ATTTTATAAGCCGGACATATGTAAACTCCTTCGGCCAAGGAACAAAGTTGACTGTTCTTGGTGGCGGAGGCAGTGGTGGCGGGGGCAGCGGAGGTGGTGGTTCAGGGGTGGTGGGAGCGAAGTCCAATTGGTAGAAAG TGGCGGTGGTCTGGTGCAACCTGGTGGATCTCTTAGCCTCTCATGCGCCGCTAGTGGCTTTACTATTTCAACTAATGCGATGAGCTGGGTTCGCCAGGCCCCCGGCAAAGGACTTGAGTGGGTCGGCGTCATCACCGGC AGGGACATTACATACTATGCGAGTTGGGCAAAGGGCAGGTTCACGATTAGCCGCGATACTTCAAAGAATACCGTTTACCTTCAAATGAATAGCTTGAGGGCGGAAGACACAGCTGTGTATTACTGCGCGAGGGATGGA GGTAGTTCCGCCATAACTTCCAACAACATATGGGGACAAGGCACGCTGGTTACTGTCTCGAGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCAGAAATCGTCCTTACACAATCTCCTAGCACACTGAGTGTGAGCCCCG GCGAACGCGCGACTTTCTCTTGCAGGGCAAGTCAATCCATAGGGACTAATATACATTGGTATCAACAAAAGCCAGGTAAACCACCCAGGCTTTTGATTAAGTATGCAAGTGAGTCTATTTCCGGTATCCCTGACCGCTT CTCTGGATCAGGCAGTGGCACAGAGTTCACACTCACCATATCTAGTGTGCAATCAGAGGACTTCGCCGTGTATTACTGCCAACAGAATAATAACTGGCCGACTACCTTCGGATGCGGTACAAAGCTGACCGTTTTACGT ACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTC CAATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCC TGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTGGCGGTGGCGGTAGCGGTGGCGGCGGAAGTGGTGGCGGAGGATCCCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGAT CACCATCTCCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTTTGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATCTATGATGTCAGTGATCGGCCCTCAGGGGTGTCTGATCGCTTC TCCGGCTCCAAGTCTGGCAACACGGCCTCCCTGATCATCTCTGGCCTCCAGGCTGACGACGAGGCTGATTATTACTGCAGCTCATATGGGAGCAGCAGCACTCATGTGATTTTCGGCGGAGGGACCAAGGTGACCGTC CTAGGTGGAGGCGGTTCAGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTCAGGTGCAATTGCAGGAGTCGGGGGGAGGCCTGGTCAAGCCTGGAGGGTCCCTGAGTCTCTCCTGTGCAGCCTCTG GATTCACCTTTAGTAGTTATTGGATGAGCTGGGTCCGCCAGGCTCCAGGAAGGGGCTGGAGTGGGTGGCCAACATAAACCGCGATGGAAGTGCGAGTTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAG AGACGACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCGTGGGGTGGGCTACTTCGATCTCTGGGGCCGTGGCACCCTGGTCACCGTCTCTAGC

>Sequence ID 71: Amino acid sequence of the heavy chain of SI-77H6

EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSG FSLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKCLEWL AHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLPP SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKGLEWIA CIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPSR FSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVYY CARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKVEIK

>Sequence ID 72: Nucleotide sequence of the heavy chain of SI-77H6

GAAATCGTCCTTACACAATCTCCTAGCACACTGAGTGTGAGCCCCGGCGAACGCGCGACTTTCTCTTGCAGGGCAAGTCAATCCATAGGGACTAATATACATTGGTATCAACAAAAGCCAGGTAAACCACCCAGGCTTTTGATTAAGTATGCAAGTGAGTCTATTTCCGGTATCCCTGACCGCTTCTCTGGATCAGGCAGTGGCACAGAGTTCACACTCACCATATCTA GTGTGCAATCAGAGGACTTCGCCGTGTATTACTGCCAACAGAATAATAACTGGCCGACTACCTTCGGACCCGGTACAAAGCTGACCGTTTTAGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCACAAGTACAGTTGCAGCAATCCGGTCCCGGTCTCGTCAAACCGAGTGAGACGCTTAGTATAACGTGTACTGTTTCAGGC TTTAGCCTTACGAACTATGGAGTTCACTGGATTCGGCAGGCACCCGGCAAAGGTTTGGAATGGCTGGGTGTTATTTGGTCAGGTGGAAATACAGACTATAACACCCCCTTTACAAGTCGGTTCACAATTACGAAAGATAATTCCAAAAATCAAGTTTATTTCAAGTTGAGATCCGTCCGCGCGGACGACACTGCGATCTACTATTGTGCGAGGGCACTGACCTACTACG ATTACGAATTTGCGTATTGGGGGCAAGGGACTCTTGTAACAGTCTCGAGCGGCGGTGGAGGGTCCGGCGGTGGTGGATCACAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGT TCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAATGTCTTGAGTGGTTG GCTCACATTTGGTGGGACGACGACAAACGGTATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCTCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTGTCGAGTGCTAGCACCAAGGGCCCAT CGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTG CAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACT GGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCA TCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATG AGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCGAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGT ACAGCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCTTCAGTAGCGGGTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCA TGCATTGCTGCTGGTAGTGCTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGATCGGCGTTTTCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTGTCGAGCGGTGGAGGCGGAT CTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGGCGGCTCTGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGG TTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAAGGCGGTGGAGGGTCCGGCGGTGGTGGCTCCGGACGGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCC TGAGACTCTCCTGTACTGCCTCTGGATTCACCATCAGTAGCTACCACATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGAACCATTAGTAGTGGTGGTAATGTATACTACGCAAGCTCCGCTAGAGGCAGATTCACCATCTCCAGACCCTCGTCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTAC TGTGCGAGAGACTCTGGTTATAGTGATCCTATGTGGGGCCAGGGAACCCTGGTCACCGTCTCTTCAGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCAGACGTTGTGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACCTGTCAGGCCAGTCAGAACATTAGGACTTACTTATCCT GGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAGCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGCCTGGCGATGCTGCAACTTACTATTGTCAGTCTACCTATCTTGGTACTGATTATGTTGGCGGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

>Sequence ID 73: Amino acid sequence of the light chain of SI-77H6

EIVMTQSPSTLSASVGDRVIITCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGAEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGQGTKLTVLGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLSLSCAASGFTISTNAMSWVRQAPGKGLEWVGVIT GRDITYYASWAKGRFTISRDTSKNTVYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSGGGGSGGGGSENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGCGTKVEIKR TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRF SGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS

>Sequence ID 74: Nucleotide sequence of the light chain of SI-77H6

GAAATCGTTATGACGCAGAGTCCCTCCACGCTCTCCGCTAGTGTCGGGGATCGCGTCATTATCACATGCCAGGCCTCCGAGTCAATCAGCAGCTGGCTTGCATGGTATCAACAGAAGCCGGGAAAAGCTCCTAAATTG CTGATCTATGAAGCGTCAAAATTGGCGTCTGGTGTCCCATCTAGGTTCTCCGGCTCTGGGTCTGGTGCGGAATTTACTTTGACAATCTCCAGTCTTCAACCAGACGATTTCGCTACCTACTACTGCCAAGGGTATTTCT ATTTTATAAGCCGGACATATGTAAACTCCTTCGGCCAAGGAACAAAGTTGACTGTTCTTGGTGGCGGAGGCAGTGGTGGCGGGGGCAGCGGAGGTGGTGGTTCAGGGGTGGTGGGAGCGAAGTCCAATTGGTAGAAA GTGGCGGTGGTCTGGTGCAACCTGGTGGATCTCTTAGCCTCTCATGCGCCGCTAGTGGCTTTACTATTTCAACTAATGCGATGAGCTGGGTTCGCCAGGCCCCCGGCAAAGGACTTGAGTGGGTCGGCGTCATCACCGG CAGGGACATTACATACTATGCGAGTTGGGCAAAGGGCAGGTTCACGATTAGCCGCGATACTTCAAAGAATACCGTTTACCTTCAAATGAATAGCTTGAGGGCGGAAGACACAGCTGTGTATTACTGCGCGAGGATGG AGGTAGTTCCGCCATAACTTCCAACAACATATGGGGACAAGGCACGCTGGTTACTGTCTCGAGCGGCGGTGGAGGGTCCGGCGGTGGTGGATCAGAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCT GGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTC AGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGTGTGGGACAAAAGTGGAGATCAAGCGTA CGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCT GAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTGGCGGTGGCGGTAGCGGTGGCGGCGGAAGTGGTGGCGGAGGATCCCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGAT CACCATCTCCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTTTGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATCTATGATGTCAGTGATCGGCCCTCAGGGGTGTCTGATCGCTTC TCCGGCTCCAAGTCTGGCAACACGGCCTCCCTGATCATCTCTGGCCTCCAGGCTGACGACGAGGCTGATTATTACTGCAGCTCATATGGGAGCAGCAGCACTCATGTGATTTTCGGCGGAGGGACCAAGGTGACCGTC CTAGGTGGAGGCGGTTCAGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTCAGGTGCAATTGCAGGAGTCGGGGGGAGGCCTGGTCAAGCCTGGAGGGTCCCTGAGTCTCTCCTGTGCAGCCTCTG GATTCACCTTTAGTAGTTATTGGATGAGCTGGGTCCGCCAGGCTCCAGGAAGGGGCTGGAGTGGGTGGCCAACATAAACCGCGATGGAAGTGCGAGTTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAG AGACGACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCGTGGGGTGGGCTACTTCGATCTCTGGGGCCGTGGCACCCTGGTCACCGTCTCTAGC

>Sequence ID 75: Amino acid sequence of the heavy chain of SI-55H11

EIVLTQSPSTLSVSPGERATFSCRASQSIGTNIHWYQQKPGKPPRLLIKYASESISGIPDRFSGSGSGTEFTLTISSVQSEDFAVYYCQQNNNWPTTFGPGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQSGPGLVKPSETLSITCTVSGF SLTNYGVHWIRQAPGKGLEWLGVIWSGGNTDYNTPFTSRFTITKDNSKNQVYFKLRSVRADDTAIYYCARALTYYDYEFAYWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPG KCLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSL GTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQV YTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKGL EWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGV PSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAV YYCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKVEIK

>Sequence ID 76: Nucleotide sequence of the heavy chain of SI-55H11

GAAATCGTCCTTACACAATCTCCTAGCACACTGAGTGTGAGCCCCGGCGAACGCGACTTTCTCTTGCAGGGCAAGTCAATCCATAGGGACTAATATACATTGGTATCAACAAAAGCCAGGTAAACCACCCAGGCTTTTGATTAAGTATGCAAGTGAGTCTATTTCCGGTATCCCTGACCGCTTCTCTGGATCAGGCAGTGGCACAGAGTTCACACTCACCATATCTAGT GTGCAATCAGAGGACTTCGCCGTGTATTACTGCCAACAGAATAATAACTGGCCGACTACCTTCGGACCCGGTACAAAGCTGACCGTTTTAGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCACAAGTACAGTTGCAGCAATCCGGTCCCGGTCTCGTCAAACCGAGTGAGACGCTTAGTATAACGTGTACTGTTTCAGGCTTT AGCCTTACGAACTATGGAGTTCACTGGATTCGGCAGGCACCCGGCAAAGGTTTGGAATGGCTGGGTGTTATTTGGTCAGGTGGAAATACAGACTATAACACCCCCTTTACAAGTCGGTTCACAATTACGAAAGATAATTCCAAAAATCAAGTTTATTTCAAGTTGAGATCCGTCCGCGCGGACGACACTGCGATCTACTATTGTGCGAGGGCACTGACCTACTACGATTAC GAATTTGCGTATTGGGGCAAGGGACTCTTGTAACAGTCTCGAGCGGTGGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGAGGTGCAGCT GGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCATCAGTACCAATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGA AGTGTCTGGAGTGGATCGGAGTCATTACTGGTCGTGATATCACATACTACGCGAGCTGGGCGAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACGGTGGTTCTTCTGCTATTACTAGTAACAACATTTGGGGCCAGGGAACCCTGGTCACCGTGTCCT CAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGG CACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCC TGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTG TACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGC TCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCGAGGTGCAGCTGTTGGAGTCTG GGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCTTCAGTAGCGGGTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTG GAGTGGATCGCATGCATTGCTGCTGGTAGTGCTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGATCGGCGTTTTCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTGTCGAGCGGT GGAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCC CATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGT TGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAAGGCGGTGGAGGGTCCGGCGGTGGTGGCTCCGGACGGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGG GGTCCCTGAGACTCTCCTGTACTGCCTCTGGATTCACCATCAGTAGCTACCACATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGAACCATTAGTAGTGGT GGTAATGTATACTACGCAAGCTCCGCTAGAGGCAGATTCACCATCTCCAGACCCTCGTCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTA TTACTGTGCGAGAGACTCTGGTTATAGTGATCCTATGTGGGGCCAGGGAACCCTGGTCACCGTCTCTTCAGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCAGACGTTGTGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACCTGTCAGGCCAGTCAGAACATTAGGACTTACTTATC CTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAGCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGCCTGGCGATGCTGCAACTTACTATTGTCAGTCTACCTATCTTGGTACTGATTATGTTGGCGGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

>Sequence ID 77: Amino acid sequence of the light chain of SI-55H11

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGGGGSGGGGSQVTLKESGPGLVQPGQTLSLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDD KRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVT INCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGCGTKVEIKR TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECGGGGSGGGGSGGGGSQSALTQPASVSGSPGQSITISCTGTSSDVGGYNFVSWYQQHPGKAPKLMIYDVSDRPSGVSDRF SGSKSGNTASLIISGLQADDEADYYCSSYGSSSTHVIFGGGTKVTVLGGGGSGGGGSGGGGSGGGGSQVQLQESGGGLVKPGGSLSLSCAASGFFSSYWMSWVRQAPGKGLEWVANINRDGSASYYVDSVKGRFTISRDDAKNSLYLQMNSLRAEDTAVYYCARDRGVGYFDLWGRGTLVTVSS

>Sequence ID 78: Nucleotide sequence of the light chain of SI-55H11

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGG ATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGT ACCCATTCACTTTCGGGCAGGGGACAAAAGTGACCGTCCTAGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCACAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCA GCCAGGACAGACCCTTAGCCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACAAA CGGTATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCTCGGATGGAACTCTGGTCTTAC TACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTCTCGAGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCAGACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCA ATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGG GACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCTGTGGGACCAAGGTGGAGATCAAACGTACG GTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAA TCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGA GCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGTGGCGGTGGCGGTAGCGGTGGCGGCGGAAGTGGTGGCGGAGGATCCCAGTCTGCCCTGACTCAGCCTGCCTCCGTGTCTGGGTCTCCTGGACAGTCGATCAC CATCTCCTGCACTGGAACCAGCAGTGACGTTGGTGGTTATAACTTTGTCTCCTGGTACCAACAACACCCAGGCAAAGCCCCCAAACTCATGATCTATGATGTCAGTGATCGGCCCTCAGGGGTGTCTGATCGCTTCTCC GGCTCCAAGTCTGGCAACACGGCCTCCCTGATCATCTCTGGCCTCCAGGCTGACGACGAGGCTGATTATTACTGCAGCTCATATGGGAGCAGCAGCACTCATGTGATTTTCGGCGGAGGGACCAAGGTGACCGTCCTA GGTGGAGGCGGTTCAGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTCAGGTGCAATTGCAGGAGTCGGGGGGAGGCCTGGTCAAGCCTGGAGGGTCCCTGAGTCTCTCCTGTGCAGCCTCTGGAT TCACCTTTAGTAGTTATTGGATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAACCGCGATGGAAGTGCGAGTTACTATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGA CGACGCCAAGAACTCACTGTATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGATCGTGGGGTGGGCTACTTCGATCTCTGGGGCCGTGGCACCCTGGTCACCGTCTCTAGCTGA

>Sequence ID 79: Amino acid sequence of the heavy chain of SI-38E17

DVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYVNSFGGGTKVEIKGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLS CAASGFTISTNAMSWVRQAPGKGLEWIGVITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSGGGGSGGGGSEVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWIGWVRQAPGKGL EWMGIIYPDDSDTRYSPSFQGQVTISADKSIRTAYLQWSSLKASDTAMYYCARHVTMIWGVIIDFWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGT QTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVY TLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKGL EWIACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQMTQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGV PSRFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVEIKGGGGSGGGGSRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVY YCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKVEIK

>Sequence ID 80: Amino acid sequence of the heavy chain of SI-38E17

GACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCAG CCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTAAATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAAGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCAGAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACTCTCCTG TGCAGCCTCTGGATTCACCATCAGTACCAATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAGTCATTACTGGTCGTGATATCACATACTACGCGAGCTGGGCGAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGCGCGACG GTGGATCATCTGCTATTACTAGTAACAACATTTGGGGCCAAGGAACTCTGGTCACCGTTTCTTCAGGCGGTGGAGGGTCCGGCGGTGGTGGATCCGAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTGAAGAAACCAGGAGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGCTTTAGCAGTTCATGGATCGGCTGGGTGCGCCAGGCACCTGGGAAAGGCCTGG AATGGATGGGGATCATCTATCCTGATGACTCTGATACCAGATACAGTCCATCCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGGACTGCCTACCTGCAGTGGAGTAGCCTGAAGGCCTCGGACACCGCTATGTATTACTGTGCGAGACATGTTACTATGATTTGGGGAGTTATTATTGACTTCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCAGCT AGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACC CAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAG GTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTAT ACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTC CGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCGAGGTGCAGCTGTTGGAGTCTGGG GGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCTTCAGTAGCGGGTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGA GTGGATCGCATGCATTGCTGCTGGTAGTGCTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGATCGGCGTTTTCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGTG GAGGCGGATCTGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCC CATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGTTTTCGGCGGAGGGACCAAGGTGGAGATCAAAGGCGGTGGAGGGTCCGGCGGTGGTGGATCCCGGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGG TCCCTGAGACTCTCCTGTACAGCCTCTGGATTCACCATCAGTAGCTACCACATGCAGTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTACATCGGAACCATTAGTAGTGGTG GTAATGTATACTACGCGAGCTCCGCGAGAGGCAGATTCACCATCTCCAGACCCTCGTCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTAT TACTGTGCGAGAGACTCTGGTTATAGTGATCCTATGTGGGGCCAGGGAACCCTGGTCACCGTCTCGAGCGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCAGACGTTGTGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACCTGTCAGGCCAGTCAGAACATTAGGACTTACTTATCC TGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAGCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGCCTGGCGATGCTGCAACTTACTATTGTCAGTCTACCTATCTTGGTACTGATTATGTTGGCGGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAA

>Sequence ID 81: Amino acid sequence of the light chain of SI-38E17

AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPFTFGPGTKVDIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>Sequence ID 82: Nucleotide sequence of the light chain of SI-38E17

GCCATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGCAGTGCTTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCTCCTAAGCTCCTGATCTATGATGCCTCCAGTT TGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGTTTAATAGTTACCCATTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAA CGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGG AGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT

>Sequence ID 83: Amino acid sequence of the heavy chain of SI-34C1

EVQLVQSGAEVKKPGESLKISCKGSGYSFSSSWIGWVRQAPGKGLEWMGIIYPDDSDTRYSPSFQGQVTISADKSIRTAYLQWSSLKASDTAMYYCARHVTMIWGVIIDFWG QGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCD KTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG

>Sequence ID 84: Nucleotide sequence of the heavy chain of SI-34C1

GAGGTGCAGCTGGTGCAGTCTGGAGCAGAGGTGAAGAAACCAGGAGAGTCTCTGAAGATCTCCTGTAAGGGTTCTGGATACAGCTTTAGCAGTTCATGGATCGGCTGGGTGCGCCAGGCACCTGGGAAAGGCCTGGAATGGATGGGGATCATCTATCCTGATGACTCT GATACCAGATACAGTCCATCCTTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGGACTGCCTACCTGCAGTGGAGTAGCCTGAAGGCCTCGGACACCGCTATGTATTACTGTGCGAGACATGTTACTATGATTTGGGGAGTTATTATTGACTTCTGGGGCC AGGGAACCCTGGTCACCGTCTCCTCAGCTAGCACCAAGGGCCCATCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAG CGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGAC AAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACTGG TACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGA AAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAA CTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGT

>Sequence ID 85: Amino acid sequence of the light chain of SI-34C1

AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQFNSYPFTFGPGTKVDIK RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>Sequence ID 86: Nucleotide sequence of the light chain of SI-34C1

GCCATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGCAGTGCTTTAGCCTGGTATCAGCAGAAACCAGGGAAAGCTCCTAAGCTCCTGATCTATGATGCCTCCAGTT TGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGATTTTGCAACTTATTACTGTCAACAGTTTAATAGTTACCCATTCACTTTCGGCCCTGGGACCAAAGTGGATATCAAA CGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAGG AGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT

>Sequence ID 87: Amino acid sequence of the heavy chain of SI-38P12

QIVLSQSPAILSASPGEKVTMTCRASSSVSYIHWFQQKPGSSPKPWIYATSNLASGVPVRFSGSGSGTSYSLTISRVEAEDAATYYCQQWTSNPPTFGGGTKLTVLGGGGSGGGGSGGGGSGGGGSQVQLQQPGAELVKPGASVKMSCKASGY TFTSYNMHWVKQTPGRGLEWIGAIYPGNGDTSYNQKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYYCARSTYYGGDWYFNVWGAGTTVTVSSGGGGSGGGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISTNAMSWVRQAPGKGLEWIG VITGRDITYYASWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGGSSAITSNNIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI CNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCAVSNKALPAPIEKTISKAKGQPREPQVYTLP PSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGGGGGSGGGGSEVQLLESGGGLVQPGGSLRLSCAASGFSFSSGYDMCWVRQAPGKGLEWI ACIAAGSAGITYDANWAKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSAFSFDYAMDLWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDIQSPSTLSASVGDRVTITCQASQSISSHLNWYQQKPGKAPKLLIYKASTLASGVPS RFSGSGSGTEFTLTISSLQPDDFATYYCQQGYSWGNVDNVFGGGTKVEIKGGGGSGGGGSGRSLVESGGGLVQPGGSLRLSCTASGFTISSYHMQWVRQAPGKGLEYIGTISSGGNVYYASSARGRFTISRPSSKNTVDLQMNSLRAEDTAVY YCARDSGYSDPMWGQGTLVTVSSGGGGSGGGGSGGGGSGGGGSDVVMTQSPSSVSASVGDRVTITCQASQNIRTYLSWYQQKPGKAPKLLIYAAANLASGVPSRFSGSGSGTDFTLTISDLEPGDAATYYCQSTYLGTDYVGGAFGGGTKVEIK

>Sequence ID 88: Nucleotide sequence of the heavy chain of SI-38P12

CAGATCGTGCTGAGCCAGAGCCCCGCCATCCTGAGCGCCAGCCCCGGCGAGAAGGTGACCATGACCTGCCGGGCCAGCAGCAGCGTGAGCTACATCCACTGGTTCCAGCAGAAGCCCGGCAGCAGCCCCAAGCCCTGGATCTACGCCACCAGCAACCTGGCCAGCGGCGTGCCCGTGCGGTTCAGCGGCAGCGGCAGCGGCACCAGCTACAGCCTGACCATCAGCCGGG TGGAGGCCGAGGACGCCGCCACCTACTACTGCCAGCAGTGGACCAGCAACCCCCCCACCTTCGGCGGCGGCACCAAGCTGACCGTGCTGGGTGGTGGTGGCTCTGGAGGAGGCGG GAGCGGGGGTGGTGGCTCAGGTGGTGGAGGTTCCCAGGTGCAGCTGCAGCAGCCCGGCGCCGAGCTGGTGAAGCCCGGCGCCAGCGTGAAGATGAGCTGCAAGGCCAGCGGCTAC ACCTTCACCAGCTACAACATGCACTGGGTGAAGCAGACCCCCGGCCGGGGCCTGGAGTGGATCGGCGCCATCTACCCCCGGCAACGGCGACACCAGCTACAACCAGAAGTTCAAGGGCAAGGCCACCCTGACCGCCGACAAGAGCAGCAGCACCGCCTACATGCAGCTGAGCAGCCTGACCAGCGAGGACAGCGCCGTGTACTACTGCGCCCGGGAGCACCTACTACGGCGG CGACTGGTACTTCAACGTGTGGGGCGCCGGCACCACCGTGACCGTCTCGAGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCAGAGGTGCAGCTGGTGGAGTCTGGGGGAGGCTTG GTCCAGCCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCACCATCAGTACCAATGCAATGAGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGGAG TCATTACTGGTCGTGATTCACATACTACGCGAGCTGGGCGAAAGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACGGTGGTTCTTCTGCTATTACTAGTAACAACATTTGGGGCCAGGGAACCCTGGTCACCGTGTCCTCAGCTAGCACCAAGGGCCCA TCGGTCTTCCCCCTGGCACCCTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGACTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGGCGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGCGTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTG CAACGTGAATCACAAGCCCAGCAACACCAAGGTGGACAAGAGAGTTGAGCCCAAATCTTGTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAAGCCGCGGGGGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGAGGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAACT GGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCGCGGTCTCCAACAAAGCCCTCCCAGCCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCA TCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATG AGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTGGCGGTGGAGGGTCCGGCGGTGGTGGATCCGAGGTGCAGCTGTTGGAGTCTGGGGGAGGCTTGGT ACAGCTGGGGGGTCCCTGAGACTCTCCTGTGCAGCCTCTGGATTCTCCTTCAGTAGCGGGTACGACATGTGCTGGGTCCGCCAGGCTCCAGGGAAGGGGCTGGAGTGGATCGCA TGCATTGCTGCTGGTAGTGCTGGTATCACTTACGACGCGAACTGGGCGAAAGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAGATCGGCGTTTTCGTTCGACTACGCCATGGACCTCTGGGGCCAGGGAACCCTGGTCACCGTGTCGAGCGGTGGAGGCGGATC TGGCGGAGGTGGTTCCGGCGGTGGCGGCTCCGGTGGAGGCGGCTCTGACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCACTTGCCAGGCCAGTCAGAGCATTAGTTCCCACTTAAACTGGTATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATAAGGCATCCACTCTGGCATCTGGGGTCCCATCAAGGT TCAGCGGCAGTGGATCTGGGACAGAATTTACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAACAGGGTTATAGTTGGGGTAATGTTGATAATGT TTTCGGCGGAGGGACCAAGGTGGAGATCAAAGGCGGTGGAGGGTCCGGCGGTGGTGGCTCCGGACGGTCGCTGGTGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTG AGACTCTCCTGTACTGCCTCTGGATTCACCATCAGTAGCTACCACATGCAGTGGGTCCGCCAGGCTCCAGGAAGGGGCTGGAGTACATCGGAACCATTAGTAGTGGTGGTAATGTATACTACGCAAGCTCCGCTAGAGGCAGATTCACCATCTCCAGACCCTCGTCCAAGAACACGGTGGATCTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTG TGCGAGAGACTCTGGTTATAGTGATCCTATGTGGGGCCAGGGAACCCTGGTCACCGTCTCTTCAGGCGGTGGCGGTAGTGGGGGAGGCGGTTCTGGCGGCGGAGGGTCCGGCGGTGGAGGATCAGACGTTGTGATGACCCAGTCTCCATCTTCCGTGTCTGCATCTGTAGGAGACAGAGTCACCATCACCTGTCAGGCCAGTCAGAACATTAGGACTTACTTATCCTGGT ATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGCTGCAGCCAATCTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGACCTGGAGCCTGGCGATGCTGCAACTTACTATTGTCAGTCTACCTATCTTGGTACTGATTATGTTGGCGGTGCTTTCGGCGGAGGGACCAAGGTGGAGATCAAATGA

>Sequence ID 89: Amino acid sequence of the light chain of SI-38P12

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGQGTKVTVLGGGGSGGGGSGG GGSGGGGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKGLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWG QGTLVTVSSGGGGSGGGGSDVVMTQSPSTLSASVGDRVTINCQASESISSWLAWYQQKPGKAPKLLIYEASKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQGYFYFISRTYV NSFGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>Sequence ID 90: Nucleotide sequence of the light chain of SI-38P12

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCC GCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGCAGGGGACAAAAGTGACGGTACTGGGTGGAGGCGGTTCAGGCGGAGGTGGTTCCGGCGGTGG CGGCTCCGGTGGAGGCGGCTCTCAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAAGGTCTTGAGTGGTTGGCTCAC ATTTGGTGGGACGACGACAAACGGTATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCGCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGC AGGGGACTCTCGTCACGGTCTCGAGCGGCGGTGGAGGGTCCGGCGGTGGTGGATCAGACGTCGTGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCATCAATTGCCAAGCCAGTGAGAGCATTAGCAGTTGGTTAGCCTGGTATCAGCAGAAACCAGG GAAAGCCCCTAAGCTCCTGATCTATGAAGCATCCAAACTGGCATCTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGATTTTGCAACTTATTACTGCCAAGGCTATTTTTATTTTATTAGTCGTACTTATGTA AATTCTTTCGGCGGAGGGACCAAGGTGGAGATCAAACGTACGGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCC AATCGGGTAACTCCCAGGAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACGCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT

>Sequence ID 91: Amino acid sequence of humanized version 7(H7VH)

QVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKCLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 92: Nucleotide sequence of humanized version 7(H7VH)

CAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAATGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACAAACGG TATAATCCTGCCTTGAAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCTCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTGTCGAGT

>Sequence ID 93: Amino acid sequence of humanized version 7(H7VL)

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGCGTKVEIK

>Sequence ID 94: Nucleotide sequence of humanized version 7(H7VL)

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTG GCTTCCGGCGTACCTAGCCGCTTCAGTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGTGTGGGACAAAAGTGGAGATCAAG

>Sequence ID 95: Amino acid sequence of SI-63SV7

ENVLTQSPASLSASPGERVTITCSASSSVSYMHWYQQKPGQAPKLWIYDTSKLASGVPSRFSGSGSGNDHTLTISSMEPEDFATYYCFQGSVYPFTFGCGTKVEIKGGGGSGGGGSGGGGSGG GGSQVTLKESGPGLVQPGQTLRLTCAFSGFSLSTSGMGVGWIRQPPGKCLEWLAHIWWDDDKRYNPALKSRLTISKDTSKNQVYLQMNSLDAEDTAVYYCARMELWSYYFDYWGQGTLVTVSS

>Sequence ID 96: Nucleic acid sequence SI-63SV7

GAAAATGTATTGACACAGAGCCCCGCCTCCCTCAGTGCCTCACCTGGGGAAAGGGTAACTATCACTTGCTCTGCATCAAGCAGCGTCTCATACATGCATTGGTATCAACAAAAGCCTGGACAGGCCCCCAAGCTCTGGATATACGATACGAGCAAGCTGGCTTCCGGCGTACCTAGCCGCTTCA GTGGTTCCGGCTCAGGCAACGATCACACCCTTACGATTTCCAGTATGGAACCCGAAGATTTTGCAACTTATTATTGTTTCCAGGGGAGCGTGTACCCATTCACTTTCGGGTGTGGGACAAAAGTGGAGATCAAGGGTGGCGGAGGCAGTGGTGGCGGGGGCAGCGGAGGTGGTGGTTCAGGGGGT GGTGGGAGCCAGGTCACATTGAAGGAATCTGGCCCCGGCCTTGTTCAGCCAGGACAGACCCTTAGGCTCACCTGTGCCTTCAGTGGTTTTTCTCTTAGCACTAGCGGTATGGGGGTCGGCTGGATTCGGCAGCCTCCCGGCAAATGTCTTGAGTGGTTGGCTCACATTTGGTGGGACGACGACA AACGGTATAATCCTGCCTTGAAAGTCGGCTGACCATTAGTAAGGATACCTCAAAAAATCAAGTGTACTTGCAAATGAATAGCCTTGACGCCGAGGATACGGCTGTATATTATTGCGCTCGGATGGAACTCTGGTCTTACTACTTTGATTATTGGGGGCAGGGGACTCTCGTCACGGTGTCGAGT

--->

LIST OF SEQUENCES

<110> SYSTEMUNE, INC.

BAILI-BAYO (CHENGDU) PHARMACEUTICAL CO., LTD.

<120> ANTIBODIES AGAINST CD19 AND METHODS OF THEIR USE AND PRODUCTION

<130>SIBA063PCT

<150> 62/984,731

<151> 2020-03-03

<160> 96

<170> PatentIn version 3.5

<210> 1

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 1

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

1 5 10 15

Thr Leu Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser

20 25 30

Gly Met Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala

50 55 60

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

65 70 75 80

Tyr Leu Gln Met Asn Ser Leu Asp Ala Glu Asp Thr Ala Val Tyr Tyr

85 90 95

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

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 2

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 2

caggtcacat tgaaggaatc tggccccggc cttgttcagc caggacagac ccttaggctc 60

acctgtgcct tcagtggttt ttctcttagc actagcggta tgggggtcgg ctggattcgg 120

cagcctcccg gcaaaggtct tgagtggttg gctcacattt ggtgggacga cgacaaacgg 180

tataatcctg ccttgaaaag tcggctgacc attagtaagg atacctcaaa aaatcaagtg 240

tacttgcaaa tgaatagcct tgacgccgag gatacggctg tatattattg cgcgcggatg 300

gaactctggt cttactactt tgattattgg gggcagggga ctctcgtcac ggtctcgagt 360

<210> 3

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 3

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

1 5 10 15

Thr Leu Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser

20 25 30

Gly Met Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala

50 55 60

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

65 70 75 80

Tyr Leu Gln Met Asn Ser Leu Asp Ala Glu Asp Thr Ala Val Tyr Tyr

85 90 95

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

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 4

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 4

caggtcacat tgaaggaatc tggccccggc cttgttcagc caggacagac ccttaggctc 60

acctgtgcct tcagtggttt ttctcttagc actagcggta tgggggtcgg ctggattcgg 120

cagcctcccg gcaaaggtct tgagtggttg gctcacattt ggtgggacga cgacaaacgg 180

tataatcctg ccttgaaaag tcggctgacc attagtaagg atacctcaaa aaatcaagtg 240

tacttgcaaa tgaatagcct tgacgccgag gatacggctg tatattattg cgcgcggatg 300

gaactctggt cttactactt tgattattgg gggcagggga ctctcgtcac ggtctcgagt 360

<210> 5

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 5

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

1 5 10 15

Thr Leu Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser

20 25 30

Gly Met Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala

50 55 60

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

65 70 75 80

Tyr Leu Gln Met Asn Ser Leu Asp Ala Glu Asp Thr Ala Val Tyr Tyr

85 90 95

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

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 6

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 6

caggtcacat tgaaggaatc tggccccggc cttgttcagc caggacagac ccttaggctc 60

acctgtgcct tcagtggttt ttctcttagc actagcggta tgggggtcgg ctggattcgg 120

cagcctcccg gcaaaggtct tgagtggttg gctcacattt ggtgggacga cgacaaacgg 180

tataatcctg ccttgaaaag tcggctgacc attagtaagg atacctcaaa aaatcaagtg 240

tacttgcaaa tgaatagcct tgacgccgag gatacggctg tatattattg cgcgcggatg 300

gaactctggt cttactactt tgattattgg gggcagggga ctctcgtcac ggtctcgagt 360

<210> 7

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 7

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

1 5 10 15

Thr Leu Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser

20 25 30

Gly Met Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala

50 55 60

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

65 70 75 80

Tyr Leu Gln Met Asn Ser Leu Asp Ala Glu Asp Thr Ala Val Tyr Tyr

85 90 95

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

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 8

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 8

caggtcacat tgaaggaatc tggccccggc cttgttcagc caggacagac ccttaggctc 60

acctgtgcct tcagtggttt ttctcttagc actagcggta tgggggtcgg ctggattcgg 120

cagcctcccg gcaaaggtct tgagtggttg gctcacattt ggtgggacga cgacaaacgg 180

tataatcctg ccttgaaaag tcggctgacc attagtaagg atacctcaaa aaatcaagtg 240

tacttgcaaa tgaatagcct tgacgccgag gatacggctg tatattattg cgcgcggatg 300

gaactctggt cttactactt tgattattgg gggcagggga ctctcgtcac ggtctcgagt 360

<210> 9

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 9

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 Val Phe Ser Gly Phe Ser Leu Ser Thr Ser

20 25 30

Gly Met Gly Val Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Trp Val Gly His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 10

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 10

gaggtgcaac ttgtggaaag cggcggcggg ttggtgcaac ctggcggttc acttcggctc 60

tcatgtgtgt tcagtggttt ttcccttagc acaagcggga tgggtgtcgg gtgggtccgc 120

caagcgcctg gcaaaggtct ggaatgggtt ggtcacattt ggtgggatga tgacaaaagg 180

tataatcccg cgctgaaatc tagatttact attagtcggg atacgagtaa gaacacggtg 240

tatctgcaaa tgaacagtct cagggcagag gatacagcgg tatattattg tgctcgaatg 300

gagctgtggt cttactattt tgattactgg ggccagggca cgttggtaac ggtctcgagt 360

<210> 11

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 11

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 Ser Phe Ser Gly Phe Ser Leu Ser Thr Ser

20 25 30

Gly Met Gly Val Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

35 40 45

Trp Val Gly His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 12

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 12

gaggtgcaac ttgtggaaag cggcggcggg ttggtgcaac ctggcggttc acttcggctc 60

tcatgtagct tcagtggttt ttcccttagc acaagcggga tgggtgtcgg gtgggtccgc 120

caagcgcctg gcaaaggtct ggaatgggtt ggtcacattt ggtgggatga tgacaaaagg 180

tataatcccg cgctgaaatc tagatttact attagtcggg atacgagtaa gaacacggtg 240

tatctgcaaa tgaacagtct cagggcagag gatacagcgg tatattattg tgctcgaatg 300

gagctgtggt cttactattt tgattactgg ggccagggca cgttggtaac ggtctcgagt 360

<210> 13

<211> 106

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 13

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 14

<211> 318

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 14

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaattgg agataaag 318

<210> 15

<211> 106

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 15

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Ile Thr Ile Leu

100 105

<210> 16

<211> 318

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 16

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaaatta cgatactg 318

<210> 17

<211> 106

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 17

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Thr Val Leu

100 105

<210> 18

<211> 318

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 18

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaactta cggtactg 318

<210> 19

<211> 106

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 19

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Val Thr Val Leu

100 105

<210> 20

<211> 318

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 20

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaagtta cggtactg 318

<210> 21

<211> 106

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 21

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

1 5 10 15

Asp Arg Val Ile Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Thr Val Leu

100 105

<210> 22

<211> 318

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 22

gaaatagtga tgacgcagtc acctagcacc cttagtgctt ctgtaggaga cagggttata 60

attacctgca gtgctagttc ctcagtgtca tacatgcact ggtatcagca gaaaccggga 120

aaagctccaa agctgcttat atacgacacg tccaaattgg catcaggtgt ccccagtcga 180

tttagtggct ctggctcagg ggctgaattt acgctcacaa tctccagcct ccaaccagat 240

gacttcgcca catactactg ttttcagggc tcagtgtatc cgtttacttt cggccagggg 300

acaaagttga ctgtactt 318

<210> 23

<211> 106

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 23

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

1 5 10 15

Asp Arg Val Ile Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Thr Val Leu

100 105

<210> 24

<211> 318

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 24

gaaatagtga tgacgcagtc acctagcacc cttagtgctt ctgtaggaga cagggttata 60

attacctgca gtgctagttc ctcagtgtca tacatgcact ggtatcagca gaaaccggga 120

aaagctccaa agctgcttat atacgacacg tccaaattgg catcaggtgt ccccagtcga 180

tttagtggct ctggctcagg ggctgaattt acgctcacaa tctccagcct ccaaccagat 240

gacttcgcca catactactg ttttcagggc tcagtgtatc cgtttacttt cggccagggg 300

acaaagttga ctgtactt 318

<210> 25

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 25

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Ser Thr Ser

20 25 30

Gly Met Gly Val Gly Trp Ile Arg Gln Pro Ser Gly Lys Gly Leu Glu

35 40 45

Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala

50 55 60

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

65 70 75 80

Phe Leu Lys Ile Ala Ser Val Asp Thr Ala Asp Thr Ala Ala Tyr Tyr

85 90 95

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

100 105 110

Gly Thr Thr Leu Thr Val Ser Ser

115 120

<210> 26

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 26

caggtgaccc tgaaagaaag cggcccgggc attctgcagc cgagccagac cctgagcctg 60

acctgcagct ttagcggctt tagcctgagc accagcggca tgggcgtggg ctggattcgc 120

cagccgagcg gcaaaggcct ggaatggctg gcgcatattt ggtgggatga tgataaacgc 180

tataacccgg cgctgaaaag ccgcctgacc attagcaaag ataccagcag caaccaggtg 240

tttctgaaaa ttgcgagcgt ggataccgcg gataccgcgg cgtattattg cgcgcgcatg 300

gaactgtgga gctattattt tgattattgg ggccagggca ccaccctgac cgtgagcagc 360

<210> 27

<211> 106

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 27

Glu Asn Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly

1 5 10 15

Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

His Trp Tyr Gln Gln Lys Ser Ser Thr Ser Pro Lys Leu Trp Ile Tyr

35 40 45

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

50 55 60

Gly Ser Gly Asn Ser His Phe Leu Thr Ile Ser Ser Met Glu Ala Glu

65 70 75 80

Asp Val Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 28

<211> 318

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 28

gaaaacgtgc tgacccagag cccggcgatt atgagcgcga gcccgggcga aaaagtgacc 60

atgacctgca gcgcgagcag cagcgtgagc tatatgcatt ggtatcagca gaaaagcagc 120

accagcccga aactgtggat ttatgatacc agcaaactgg cgagcggcgt gccgggccgc 180

tttagcggca gcggcagcgg caacagccat tttctgacca ttagcagcat ggaagcggaa 240

gatgtggcga cctattattg ctttcagggc agcgtgtatc cgtttacctt tggcagcggc 300

accaaactgg aaattaaa 318

<210> 29

<211> 121

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 29

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

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Ser Ser

20 25 30

Trp Ile Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Asp Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Arg Thr Ala Tyr

65 70 75 80

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

85 90 95

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

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 30

<211> 363

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 30

gaggtgcagc tggtgcagtc tggagcagag gtgaagaaac caggagagtc tctgaagatc 60

tcctgtaagg gttctggata cagctttagc agttcatgga tcggctgggt gcgccaggca 120

cctgggaaag gcctggaatg gatggggatc atctatcctg atgactctga taccagatac 180

agtccatcct tccaaggcca ggtcaccatc tcagccgaca agtccatcag gactgcctac 240

ctgcagtgga gtagcctgaa ggcctcggac accgctatgt attactgtgc gagacatgtt 300

actatgattt ggggagttat tattgacttc tggggccagg gaaccctggt caccgtctcc 360

tca 363

<210> 31

<211> 107

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 31

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Ala

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Phe Asn Ser Tyr Pro Phe

85 90 95

Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 32

<211> 321

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 32

gccatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gggcattagc agtgctttag cctggtatca gcagaaacca 120

gggaaagctc ctaagctcct gatctatgat gcctccagtt tggaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagatttg caacttatta ctgtcaacag tttaatagtt acccattcac tttcggccct 300

gggaccaaag tggatatcaa a 321

<210> 33

<211> 449

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 33

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser Leu Ser Thr Ser

20 25 30

Gly Met Gly Val Gly Trp Ile Arg Gln Pro Ser Gly Lys Gly Leu Glu

35 40 45

Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala

50 55 60

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

65 70 75 80

Phe Leu Lys Ile Ala Ser Val Asp Thr Ala Asp Thr Ala Ala Tyr Tyr

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

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

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp

210 215 220

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

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

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

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

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

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

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

420 425 430

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

435 440 445

Lys

<210> 34

<211> 1347

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 34

caggtgaccc tgaaagaaag cggcccgggc attctgcagc cgagccagac cctgagcctg 60

acctgcagct ttagcggctt tagcctgagc accagcggca tgggcgtggg ctggattcgc 120

cagccgagcg gcaaaggcct ggaatggctg gcgcatattt ggtgggatga tgataaacgc 180

tataacccgg cgctgaaaag ccgcctgacc attagcaaag ataccagcag caaccaggtg 240

tttctgaaaa ttgcgagcgt ggataccgcg gataccgcgg cgtattattg cgcgcgcatg 300

gaactgtgga gctattattt tgattattgg ggccagggca ccaccctgac cgtgagcagc 360

gctagcacca agggcccatc tgtcttcccc ctggcaccct cctccaagag cacctctggg 420

ggcacagctg ccctgggctg cctggtcaag gactacttcc ctgaacctgt gacagtgtcc 480

tggaactcag gagccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctcctgt agcaggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacgccagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 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 cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacacag 1320

aagagcctct ccctgtctcc gggcaaa 1347

<210> 35

<211> 213

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 35

Glu Asn Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly

1 5 10 15

Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

His Trp Tyr Gln Gln Lys Ser Ser Thr Ser Pro Lys Leu Trp Ile Tyr

35 40 45

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

50 55 60

Gly Ser Gly Asn Ser His Phe Leu Thr Ile Ser Ser Met Glu Ala Glu

65 70 75 80

Asp Val Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro

100 105 110

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

115 120 125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135 140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155 160

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

165 170 175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185 190

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

195 200 205

AsnArgGlyGluCys

210

<210> 36

<211> 639

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 36

gaaaacgtgc tgacccagag cccggcgatt atgagcgcga gcccgggcga aaaagtgacc 60

atgacctgca gcgcgagcag cagcgtgagc tatatgcatt ggtatcagca gaaaagcagc 120

accagcccga aactgtggat ttatgatacc agcaaactgg cgagcggcgt gccgggccgc 180

tttagcggca gcggcagcgg caacagccat tttctgacca ttagcagcat ggaagcggaa 240

gatgtggcga cctattattg ctttcagggc agcgtgtatc cgtttacctt tggcagcggc 300

accaaactgg aaattaaacg tacggtggct gcaccatctg tcttcatctt cccgccatct 360

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 600

agctcgcccg tcacaaagag cttcaacagg gggagagtgt 639

<210> 37

<211> 449

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 37

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

1 5 10 15

Thr Leu Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser

20 25 30

Gly Met Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala

50 55 60

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

65 70 75 80

Tyr Leu Gln Met Asn Ser Leu Asp Ala Glu Asp Thr Ala Val Tyr Tyr

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

165 170 175

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

180 185 190

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

195 200 205

Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp

210 215 220

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

225 230 235 240

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

245 250 255

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

260 265 270

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

275 280 285

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

290 295 300

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

305 310 315 320

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

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

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

420 425 430

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

435 440 445

Lys

<210> 38

<211> 1347

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 38

caggtcacat tgaaggaatc tggccccggc cttgttcagc caggacagac ccttaggctc 60

acctgtgcct tcagtggttt ttctcttagc actagcggta tgggggtcgg ctggattcgg 120

cagcctcccg gcaaaggtct tgagtggttg gctcacattt ggtgggacga cgacaaacgg 180

tataatcctg ccttgaaaag tcggctgacc attagtaagg atacctcaaa aaatcaagtg 240

tacttgcaaa tgaatagcct tgacgccgag gatacggctg tatattattg cgcgcggatg 300

gaactctggt cttactactt tgattattgg gggcagggga ctctcgtcac ggtgtcctct 360

gctagcacca agggcccatc tgtcttcccc ctggcaccct cctccaagag cacctctggg 420

ggcacagctg ccctgggctg cctggtcaag gactacttcc ctgaacctgt gacagtgtcc 480

tggaactcag gagccctgac cagcggcgtg cacaccttcc cggctgtcct acagtcctca 540

ggactctact ccctcagcag cgtggtgacc gtgccctcca gcagcttggg cacccagacc 600

tacatctgca acgtgaatca caagcccagc aacaccaagg tggacaagaa agttgagccc 660

aaatcttgtg acaaaactca cacatgccca ccgtgcccag cacctcctgt agcaggaccg 720

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 780

gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 840

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacgccagc 900

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 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 cctctacagc aagctcaccg tggacaagag caggtggcag 1260

caggggaacg tcttctcatg ctccgtgatg catgaggctc tgcacaacca ctacacacag 1320

aagagcctct ccctgtctcc gggcaaa 1347

<210> 39

<211> 213

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 39

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

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

100 105 110

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

115 120 125

Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys

130 135 140

Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu

145 150 155 160

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

165 170 175

Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala

180 185 190

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

195 200 205

AsnArgGlyGluCys

210

<210> 40

<211> 639

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 40

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaattgg agataaagcg tacggtggct gcaccatctg tcttcatctt cccgccatct 360

gatgagcagt tgaaatctgg aactgcctct gttgtgtgcc tgctgaataa cttctatccc 420

agagaggcca aagtacagtg gaaggtggat aacgccctcc aatcgggtaa ctcccaggag 480

agtgtcacag agcaggacag caaggacagc acctacagcc tcagcagcac cctgacgctg 540

agcaaagcag actacgagaa acacaaagtc tacgcctgcg aagtcaccca tcagggcctg 600

agctcgcccg tcacaaagag cttcaacagg gggagagtgt 639

<210> 41

<211> 254

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 41

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

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

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser Gly Ser His His His His His

245 250

<210> 42

<211> 765

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 42

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaattgg agataaaggg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttaggctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg cgcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagtgg atcccatcat caccatcacc attga 765

<210> 43

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 43

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

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

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser

245

<210> 44

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 44

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaattgg agataaaggg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttaggctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg cgcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagt 738

<210> 45

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 45

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Ile Thr Ile Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser

245

<210> 46

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 46

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaaatta cgatactggg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttaggctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg cgcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagt 738

<210> 47

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 47

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser

245

<210> 48

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 48

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaattga cggtactggg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttaggctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg cgcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagt 738

<210> 49

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 49

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser

245

<210> 50

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 50

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaagtta cggtactggg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttaggctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg cgcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagt 738

<210> 51

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 51

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

1 5 10 15

Asp Arg Val Ile Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val

115 120 125

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

130 135 140

Arg Leu Ser Cys Val Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

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

165 170 175

Gly His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser

245

<210> 52

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 52

gaaatagtga tgacgcagtc acctagcacc cttagtgctt ctgtaggaga cagggttata 60

attacctgca gtgctagttc ctcagtgtca tacatgcact ggtatcagca gaaaccggga 120

aaagctccaa agctgcttat atacgacacg tccaaattgg catcaggtgt ccccagtcga 180

tttagtggct ctggctcagg ggctgaattt acgctcacaa tctccagcct ccaaccagat 240

gacttcgcca catactactg ttttcagggc tcagtgtatc cgtttacttt cggccagggg 300

acaaagttga ctgtacttgg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaga ggtgcaactt gtggaaagcg gcggcgggtt ggtgcaacct 420

ggcggttcac ttcggctctc atgtgtgttc agtggttttt cccttagcac aagcgggatg 480

ggtgtcgggt gggtccgcca agcgcctggc aaaggtctgg aatgggttgg tcacatttgg 540

tgggatgatg acaaaaggta taatcccgcg ctgaaatcta gatttactat tagtcgggat 600

acgagtaaga acacggtgta tctgcaaatg aacagtctca gggcagagga tacagcggta 660

tattattgtg ctcgaatgga gctgtggtct tactattttg attactgggg ccagggcacg 720

ttggtaacgg tctcgagt 738

<210> 53

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 53

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

1 5 10 15

Asp Arg Val Ile Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val

115 120 125

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

130 135 140

Arg Leu Ser Cys Ser Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

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

165 170 175

Gly His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser

245

<210> 54

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 54

gaaatagtga tgacgcagtc acctagcacc cttagtgctt ctgtaggaga cagggttata 60

attacctgca gtgctagttc ctcagtgtca tacatgcact ggtatcagca gaaaccggga 120

aaagctccaa agctgcttat atacgacacg tccaaattgg catcaggtgt ccccagtcga 180

tttagtggct ctggctcagg ggctgaattt acgctcacaa tctccagcct ccaaccagat 240

gacttcgcca catactactg ttttcagggc tcagtgtatc cgtttacttt cggccagggg 300

acaaagttga ctgtacttgg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaga ggtgcaactt gtggaaagcg gcggcgggtt ggtgcaacct 420

ggcggttcac ttcggctctc atgtagcttc agtggttttt cccttagcac aagcgggatg 480

ggtgtcgggt gggtccgcca agcgcctggc aaaggtctgg aatgggttgg tcacatttgg 540

tgggatgatg acaaaaggta taatcccgcg ctgaaatcta gatttactat tagtcgggat 600

acgagtaaga acacggtgta tctgcaaatg aacagtctca gggcagagga tacagcggta 660

tattattgtg ctcgaatgga gctgtggtct tactattttg attactgggg ccagggcacg 720

ttggtaacgg tctcgagt 738

<210> 55

<211> 507

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 55

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

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

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser Gly Gly Ser Ser Gly Ser Gly Ser Gly Ser

245 250 255

Thr Gly Leu Val Pro Arg Gly Ser Thr Ser Ser Ser Gly Thr Gly Thr

260 265 270

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

275 280 285

Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys

290 295 300

Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp

305 310 315 320

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu

325 330 335

Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu

340 345 350

His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn

355 360 365

Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly

370 375 380

Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu

385 390 395 400

Leu Thr Lys Asn Gln Val Ser Leu Arg Cys His Val Lys Gly Phe Tyr

405 410 415

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

420 425 430

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

435 440 445

Leu Tyr Ser Thr Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn

450 455 460

Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr

465 470 475 480

Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Ser Gly Leu Asn Asp

485 490 495

Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu

500 505

<210> 56

<211> 1521

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 56

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaattgg agataaaggg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttaggctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg cgcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagtgg gggatcctct ggaagtggct ccggcagcac tgggctcgta 780

ccaagggggt ccacatccag tagcggtact ggcacatccg cgggaacccc cgtcgctgga 840

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 900

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 960

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacgct 1020

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1080

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1140

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 1200

ctgaccaaga accaggtcag cctgagatgc cacgtcaaag gcttctatcc cagcgacatc 1260

gccgtggagt ggggagagcaa tgggcagccg gagaacaact acaagaccac gaagcccgtg 1320

ctggactccg acggctcctt cttcctctac agcaccctca ccgtggacaa gagcaggtgg 1380

cagcagggga acgtcttctc atgctccgtg ctccatgagg ctctgcacaa cactacaca 1440

cagaagagcc tctccctgtc tccgggcaaa ggttcaggcc tgaacgatat ttttgaagcg 1500

cagaaaattg aatggcatga a 1521

<210> 57

<211> 507

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 57

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Ile Thr Ile Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser Gly Gly Ser Ser Gly Ser Gly Ser Gly Ser

245 250 255

Thr Gly Leu Val Pro Arg Gly Ser Thr Ser Ser Ser Gly Thr Gly Thr

260 265 270

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

275 280 285

Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys

290 295 300

Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp

305 310 315 320

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu

325 330 335

Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu

340 345 350

His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn

355 360 365

Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly

370 375 380

Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu

385 390 395 400

Leu Thr Lys Asn Gln Val Ser Leu Arg Cys His Val Lys Gly Phe Tyr

405 410 415

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

420 425 430

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

435 440 445

Leu Tyr Ser Thr Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn

450 455 460

Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr

465 470 475 480

Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Ser Gly Leu Asn Asp

485 490 495

Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu

500 505

<210> 58

<211> 1521

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 58

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaaatta cgatactggg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttaggctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg cgcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagtgg gggatcctct ggaagtggct ccggcagcac tgggctcgta 780

ccaagggggt ccacatccag tagcggtact ggcacatccg cgggaacccc cgtcgctgga 840

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 900

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 960

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacgct 1020

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1080

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1140

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 1200

ctgaccaaga accaggtcag cctgagatgc cacgtcaaag gcttctatcc cagcgacatc 1260

gccgtggagt ggggagagcaa tgggcagccg gagaacaact acaagaccac gaagcccgtg 1320

ctggactccg acggctcctt cttcctctac agcaccctca ccgtggacaa gagcaggtgg 1380

cagcagggga acgtcttctc atgctccgtg ctccatgagg ctctgcacaa cactacaca 1440

cagaagagcc tctccctgtc tccgggcaaa ggttcaggcc tgaacgatat ttttgaagcg 1500

cagaaaattg aatggcatga a 1521

<210> 59

<211> 507

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 59

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser Gly Gly Ser Ser Gly Ser Gly Ser Gly Ser

245 250 255

Thr Gly Leu Val Pro Arg Gly Ser Thr Ser Ser Ser Gly Thr Gly Thr

260 265 270

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

275 280 285

Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys

290 295 300

Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp

305 310 315 320

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu

325 330 335

Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu

340 345 350

His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn

355 360 365

Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly

370 375 380

Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu

385 390 395 400

Leu Thr Lys Asn Gln Val Ser Leu Arg Cys His Val Lys Gly Phe Tyr

405 410 415

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

420 425 430

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

435 440 445

Leu Tyr Ser Thr Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn

450 455 460

Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr

465 470 475 480

Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Ser Gly Leu Asn Asp

485 490 495

Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu

500 505

<210> 60

<211> 1521

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 60

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaactta cggtactggg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttaggctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg cgcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagtgg gggatcctct ggaagtggct ccggcagcac tgggctcgta 780

ccaagggggt ccacatccag tagcggtact ggcacatccg cgggaacccc cgtcgctgga 840

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 900

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 960

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacgct 1020

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1080

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1140

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 1200

ctgaccaaga accaggtcag cctgagatgc cacgtcaaag gcttctatcc cagcgacatc 1260

gccgtggagt ggggagagcaa tgggcagccg gagaacaact acaagaccac gaagcccgtg 1320

ctggactccg acggctcctt cttcctctac agcaccctca ccgtggacaa gagcaggtgg 1380

cagcagggga acgtcttctc atgctccgtg ctccatgagg ctctgcacaa cactacaca 1440

cagaagagcc tctccctgtc tccgggcaaa ggttcaggcc tgaacgatat ttttgaagcg 1500

cagaaaattg aatggcatga a 1521

<210> 61

<211> 507

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 61

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser Gly Gly Ser Ser Gly Ser Gly Ser Gly Ser

245 250 255

Thr Gly Leu Val Pro Arg Gly Ser Thr Ser Ser Ser Gly Thr Gly Thr

260 265 270

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

275 280 285

Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys

290 295 300

Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp

305 310 315 320

Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu

325 330 335

Glu Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu

340 345 350

His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn

355 360 365

Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly

370 375 380

Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu

385 390 395 400

Leu Thr Lys Asn Gln Val Ser Leu Arg Cys His Val Lys Gly Phe Tyr

405 410 415

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

420 425 430

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

435 440 445

Leu Tyr Ser Thr Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn

450 455 460

Val Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr

465 470 475 480

Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Gly Ser Gly Leu Asn Asp

485 490 495

Ile Phe Glu Ala Gln Lys Ile Glu Trp His Glu

500 505

<210> 62

<211> 1521

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 62

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaagtta cggtactggg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttaggctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg cgcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagtgg gggatcctct ggaagtggct ccggcagcac tgggctcgta 780

ccaagggggt ccacatccag tagcggtact ggcacatccg cgggaacccc cgtcgctgga 840

ccgtcagtct tcctcttccc cccaaaaccc aaggacaccc tcatgatctc ccggacccct 900

gaggtcacat gcgtggtggt ggacgtgagc cacgaagacc ctgaggtcaa gttcaactgg 960

tacgtggacg gcgtggaggt gcataatgcc aagacaaagc cgcgggagga gcagtacgct 1020

agcacgtacc gtgtggtcag cgtcctcacc gtcctgcacc aggactggct gaatggcaag 1080

gagtacaagt gcaaggtctc caacaaagcc ctcccagccc ccatcgagaa aaccatctcc 1140

aaagccaaag ggcagccccg agaaccacag gtgtacaccc tgcccccatc ccgggatgag 1200

ctgaccaaga accaggtcag cctgagatgc cacgtcaaag gcttctatcc cagcgacatc 1260

gccgtggagt ggggagagcaa tgggcagccg gagaacaact acaagaccac gaagcccgtg 1320

ctggactccg acggctcctt cttcctctac agcaccctca ccgtggacaa gagcaggtgg 1380

cagcagggga acgtcttctc atgctccgtg ctccatgagg ctctgcacaa cactacaca 1440

cagaagagcc tctccctgtc tccgggcaaa ggttcaggcc tgaacgatat ttttgaagcg 1500

cagaaaattg aatggcatga a 1521

<210> 63

<211> 506

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 63

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

1 5 10 15

Asp Arg Val Ile Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val

115 120 125

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

130 135 140

Arg Leu Ser Cys Val Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

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

165 170 175

Gly His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser Gly Ser Ser Gly Ser Gly Ser Gly Ser Thr

245 250 255

Gly Leu Val Pro Arg Gly Ser Thr Ser Ser Ser Gly Thr Gly Thr Ser

260 265 270

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

275 280 285

Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val

290 295 300

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

305 310 315 320

Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu

325 330 335

Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His

340 345 350

Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys

355 360 365

Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln

370 375 380

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu

385 390 395 400

Thr Lys Asn Gln Val Ser Leu Arg Cys His Val Lys Gly Phe Tyr Pro

405 410 415

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

420 425 430

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

435 440 445

Tyr Ser Thr Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val

450 455 460

Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln

465 470 475 480

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

485 490 495

Phe Glu Ala Gln Lys Ile Glu Trp His Glu

500 505

<210> 64

<211> 1518

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 64

gaaatagtga tgacgcagtc acctagcacc cttagtgctt ctgtaggaga cagggttata 60

attacctgca gtgctagttc ctcagtgtca tacatgcact ggtatcagca gaaaccggga 120

aaagctccaa agctgcttat atacgacacg tccaaattgg catcaggtgt ccccagtcga 180

tttagtggct ctggctcagg ggctgaattt acgctcacaa tctccagcct ccaaccagat 240

gacttcgcca catactactg ttttcagggc tcagtgtatc cgtttacttt cggccagggg 300

acaaagttga ctgtacttgg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaga ggtgcaactt gtggaaagcg gcggcgggtt ggtgcaacct 420

ggcggttcac ttcggctctc atgtgtgttc agtggttttt cccttagcac aagcgggatg 480

ggtgtcgggt gggtccgcca agcgcctggc aaaggtctgg aatgggttgg tcacatttgg 540

tgggatgatg acaaaaggta taatcccgcg ctgaaatcta gatttactat tagtcgggat 600

acgagtaaga acacggtgta tctgcaaatg aacagtctca gggcagagga tacagcggta 660

tattattgtg ctcgaatgga gctgtggtct tactattttg attactgggg ccagggcacg 720

ttggtaacgg tctcgagtgg atcctctgga agtggctccg gcagcactgg gctcgtacca 780

agggggtcca catccagtag cggtactggc acatccgcgg gaacccccgt cgctggaccg 840

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 900

gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 960

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacgctagc 1020

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 1080

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1140

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1200

accaagaacc aggtcagcct gagatgccac gtcaaaggct tctatcccag cgacatcgcc 1260

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgaa gcccgtgctg 1320

gactccgacg gctccttctt cctctacagc accctcaccg tggacaagag caggtggcag 1380

caggggaacg tcttctcatg ctccgtgctc catgaggctc tgcacaacca ctacacacag 1440

aagagcctct ccctgtctcc gggcaaaggt tcaggcctga acgatatttt tgaagcgcag 1500

aaaattgaat ggcatgaa 1518

<210> 65

<211> 506

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 65

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

1 5 10 15

Asp Arg Val Ile Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val

115 120 125

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

130 135 140

Arg Leu Ser Cys Ser Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

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

165 170 175

Gly His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser Gly Ser Ser Gly Ser Gly Ser Gly Ser Thr

245 250 255

Gly Leu Val Pro Arg Gly Ser Thr Ser Ser Ser Gly Thr Gly Thr Ser

260 265 270

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

275 280 285

Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val

290 295 300

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

305 310 315 320

Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu

325 330 335

Gln Tyr Ala Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His

340 345 350

Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys

355 360 365

Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln

370 375 380

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu

385 390 395 400

Thr Lys Asn Gln Val Ser Leu Arg Cys His Val Lys Gly Phe Tyr Pro

405 410 415

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

420 425 430

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

435 440 445

Tyr Ser Thr Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val

450 455 460

Phe Ser Cys Ser Val Leu His Glu Ala Leu His Asn His Tyr Thr Gln

465 470 475 480

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

485 490 495

Phe Glu Ala Gln Lys Ile Glu Trp His Glu

500 505

<210> 66

<211> 1518

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 66

gaaatagtga tgacgcagtc acctagcacc cttagtgctt ctgtaggaga cagggttata 60

attacctgca gtgctagttc ctcagtgtca tacatgcact ggtatcagca gaaaccggga 120

aaagctccaa agctgcttat atacgacacg tccaaattgg catcaggtgt ccccagtcga 180

tttagtggct ctggctcagg ggctgaattt acgctcacaa tctccagcct ccaaccagat 240

gacttcgcca catactactg ttttcagggc tcagtgtatc cgtttacttt cggccagggg 300

acaaagttga ctgtacttgg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaga ggtgcaactt gtggaaagcg gcggcgggtt ggtgcaacct 420

ggcggttcac ttcggctctc atgtagcttc agtggttttt cccttagcac aagcgggatg 480

ggtgtcgggt gggtccgcca agcgcctggc aaaggtctgg aatgggttgg tcacatttgg 540

tgggatgatg acaaaaggta taatcccgcg ctgaaatcta gatttactat tagtcgggat 600

acgagtaaga acacggtgta tctgcaaatg aacagtctca gggcagagga tacagcggta 660

tattattgtg ctcgaatgga gctgtggtct tactattttg attactgggg ccagggcacg 720

ttggtaacgg tctcgagtgg atcctctgga agtggctccg gcagcactgg gctcgtacca 780

agggggtcca catccagtag cggtactggc acatccgcgg gaacccccgt cgctggaccg 840

tcagtcttcc tcttcccccc aaaacccaag gacaccctca tgatctcccg gacccctgag 900

gtcacatgcg tggtggtgga cgtgagccac gaagaccctg aggtcaagtt caactggtac 960

gtggacggcg tggaggtgca taatgccaag acaaagccgc gggaggagca gtacgctagc 1020

acgtaccgtg tggtcagcgt cctcaccgtc ctgcaccagg actggctgaa tggcaaggag 1080

tacaagtgca aggtctccaa caaagccctc ccagccccca tcgagaaaac catctccaaa 1140

gccaaagggc agccccgaga accacaggtg tacaccctgc ccccatcccg ggatgagctg 1200

accaagaacc aggtcagcct gagatgccac gtcaaaggct tctatcccag cgacatcgcc 1260

gtggagtggg agagcaatgg gcagccggag aacaactaca agaccacgaa gcccgtgctg 1320

gactccgacg gctccttctt cctctacagc accctcaccg tggacaagag caggtggcag 1380

caggggaacg tcttctcatg ctccgtgctc catgaggctc tgcacaacca ctacacacag 1440

aagagcctct ccctgtctcc gggcaaaggt tcaggcctga acgatatttt tgaagcgcag 1500

aaaattgaat ggcatgaa 1518

<210> 67

<211> 1223

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 67

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Ser Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

245 250 255

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

260 265 270

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

275 280 285

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

290 295 300

Gly Val Ile Trp Ser Gly Gly Asn Thr Asp Tyr Asn Thr Pro Phe Thr

305 310 315 320

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

325 330 335

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

340 345 350

Arg Ala Leu Thr Tyr Tyr Asp Tyr Glu Phe Ala Tyr Trp Gly Gln Gly

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu

420 425 430

Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser

435 440 445

Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro

450 455 460

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

465 470 475 480

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro

485 490 495

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

500 505 510

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

515 520 525

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

530 535 540

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

545 550 555 560

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

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

660 665 670

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

675 680 685

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

690 695 700

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

705 710 715 720

Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys

725 730 735

Ala Ala Ser Gly Phe Ser Phe Ser Ser Gly Tyr Asp Met Cys Trp Val

740 745 750

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

755 760 765

Gly Ser Ala Gly Ile Thr Tyr Asp Ala Asn Trp Ala Lys Gly Arg Phe

770 775 780

Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn

785 790 795 800

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

805 810 815

Phe Ser Phe Asp Tyr Ala Met Asp Leu Trp Gly Gln Gly Thr Leu Val

820 825 830

Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

835 840 845

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

850 855 860

Ser Thr Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln

865 870 875 880

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

885 890 895

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

900 905 910

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr

915 920 925

Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp Phe Ala Thr Tyr Tyr Cys

930 935 940

Gln Gln Gly Tyr Ser Trp Gly Asn Val Asp Asn Val Phe Gly Gly Gly

945 950 955 960

Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

965 970 975

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

980 985 990

Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Ile Ser Ser Tyr

995 1000 1005

His Met Gln Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Tyr

1010 1015 1020

Ile Gly Thr Ile Ser Ser Gly Gly Asn Val Tyr Tyr Ala Ser Ser

1025 1030 1035

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

1040 1045 1050

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

1055 1060 1065

Tyr Tyr Cys Ala Arg Asp Ser Gly Tyr Ser Asp Pro Met Trp Gly

1070 1075 1080

Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly

1085 1090 1095

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp

1100 1105 1110

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

1115 1120 1125

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

1130 1135 1140

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

1145 1150 1155

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

1160 1165 1170

Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

1175 1180 1185

Asp Leu Glu Pro Gly Asp Ala Ala Thr Tyr Tyr Cys Gln Ser Thr

1190 1195 1200

Tyr Leu Gly Thr Asp Tyr Val Gly Gly Ala Phe Gly Gly Gly Thr

1205 1210 1215

Lys Val Glu Ile Lys

1220

<210> 68

<211> 3672

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 68

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaagtga ccgtcctagg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttagcctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg ctcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagtgg cggtggaggg tccggcggtg gtggatcaca agtacagttg 780

cagcaatccg gtcccggtct cgtcaaaccg agtgagacgc ttagtataac gtgtactgtt 840

tcaggcttta gccttacgaa ctatggagtt cactggattc ggcaggcacc cggcaaatgt 900

ttggaatggc tgggtgttat ttggtcaggt ggaaatacag actataacac cccctttaca 960

agtcggttca caattacgaa agataattcc aaaaatcaag tttatttcaa gttgagatcc 1020

gtccgcgcgg acgacactgc gatctactat tgtgcgaggg cactgaccta ctacgattac 1080

gaatttgcgt attggggggca agggactctt gtaacagtct ccagtgctag caccaagggc 1140

ccatcggtct tccccctggc accctcctcc aagagcacct ctggggggcac agcggccctg 1200

ggctgcctgg tcaaggacta cttccccgaa ccggtgacgg tgtcgtggaa ctcaggcgcc 1260

ctgaccagcg gcgtgcacac cttcccggct gtcctacagt cctcaggact ctactccctc 1320

agcagcgtgg tgaccgtgcc ctccagcagc ttgggcaccc agacctacat ctgcaacgtg 1380

aatcacaagc ccagcaacac caaggtggac aagagagttg agcccaaatc ttgtgacaaa 1440

actcacacat gcccaccgtg cccagcacct gaagccgcgg gggcaccgtc agtcttcctc 1500

ttccccccaa aacccaagga caccctcatg atctcccgga cccctgaggt cacatgcgtg 1560

gtggtggacg tgagccacga agaccctgag gtcaagttca actggtacgt ggacggcgtg 1620

gaggtgcata atgccaagac aaagccgcgg gaggagcagt acaacagcac gtaccgtgtg 1680

gtcagcgtcc tcaccgtcct gcaccaggac tggctgaatg gcaaggagta caagtgcgcg 1740

gtctccaaca aagccctccc agcccccatc gagaaaacca tctccaaagc caaagggcag 1800

ccccgagaac cacaggtgta caccctgccc ccatcccggg atgagctgac caagaaccag 1860

gtcagcctga cctgcctggt caaaggcttc tatcccagcg acatcgccgt ggagtgggag 1920

agcaatgggc agccggagaa caactacaag accacgcctc ccgtgctgga ctccgacggc 1980

tccttcttcc tctatagcaa gctcaccgtg gacaagagca ggtggcagca ggggaacgtc 2040

ttctcatgct ccgtgatgca tgaggctctg cacaaccact acacgcagaa gagcctctcc 2100

ctgtctccgg gtggcggtgg agggtccggc ggtggtggat ccgaggtgca gctgttggag 2160

tctgggggag gcttggtaca gcctgggggg tccctgagac tctcctgtgc agcctctgga 2220

ttctccttca gtagcgggta cgacatgtgc tgggtccgcc aggctccagg gaaggggctg 2280

gagtggatcg catgcattgc tgctggtagt gctggtatca cttacgacgc gaactgggcg 2340

aaaggccggt tcaccatctc cagagacaat tccaagaaca cgctgtatct gcaaatgaac 2400

agcctgagag ccgaggacac ggccgtatat tactgtgcga gatcggcgtt ttcgttcgac 2460

tacgccatgg acctctgggg ccagggaacc ctggtcaccg tgtcgagcgg tggaggcgga 2520

tctggcggag gtggttccgg cggtggcggc tccggtggag gcggctctga catccagatg 2580

acccagtctc cttccaccct gtctgcatct gtaggagaca gagtcaccat cacttgccag 2640

gccagtcaga gcattagttc ccacttaaac tggtatcagc agaaaccagg gaaagcccct 2700

aagctcctga tctataaggc atccactctg gcatctgggg tcccatcaag gttcagcggc 2760

agtggatctg ggacagaatt tactctcacc atcagcagcc tgcagcctga tgattttgca 2820

acttattact gccaacaggg ttatagttgg ggtaatgttg ataatgtttt cggcggaggg 2880

accaaggtgg agatcaaagg cggtggaggg tccggcggtg gtggctccgg acggtcgctg 2940

gtggagtctg ggggaggctt ggtccagcct ggggggtccc tgagactctc ctgtactgcc 3000

tctggattca ccatcagtag ctaccacatg cagtgggtcc gccaggctcc agggaagggg 3060

ctggagtaca tcggaaccat tagtagtggt ggtaatgtat actacgcaag ctccgctaga 3120

ggcagattca ccatctccag accctcgtcc aagaacacgg tggatcttca aatgaacagc 3180

ctgagagccg aggacacggc tgtgtattac tgtgcgagag actctggtta tagtgatcct 3240

atgtggggcc agggaaccct ggtcaccgtc tcttcaggcg gtggcggtag tgggggaggc 3300

ggttctggcg gcggagggtc cggcggtgga ggatcagacg ttgtgatgac ccagtctcca 3360

tcttccgtgt ctgcatctgt aggagacaga gtcaccatca cctgtcaggc cagtcagaac 3420

attaggactt acttatcctg gtatcagcag aaaccagga aagcccctaa gctcctgatc 3480

tatgctgcag ccaatctggc atctggggtc ccatcaaggt tcagcggcag tggatctggg 3540

acagatttca ctctcaccat cagcgacctg gagcctggcg atgctgcaac ttactattgt 3600

cagtctacct atcttggtac tgattatgtt ggcggtgctt tcggcggagg gaccaaggtg 3660

gagatcaaat ga 3672

<210> 69

<211> 740

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 69

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

1 5 10 15

Asp Arg Val Ile Ile Thr Cys Gln Ala Ser Glu Ser Ile Ser Ser Trp

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gly Tyr Phe Tyr Phe Ile Ser

85 90 95

Arg Thr Tyr Val Asn Ser Phe Gly Gln Gly Thr Lys Leu Thr Val Leu

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

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

130 135 140

Gln Pro Gly Gly Ser Leu Ser Leu Ser Cys Ala Ala Ser Gly Phe Thr

145 150 155 160

Ile Ser Thr Asn Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly

165 170 175

Leu Glu Trp Val Gly Val Ile Thr Gly Arg Asp Ile Thr Tyr Tyr Ala

180 185 190

Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Arg Asp Thr Ser Lys Asn

195 200 205

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

210 215 220

Tyr Tyr Cys Ala Arg Asp Gly Gly Ser Ser Ala Ile Thr Ser Asn Asn

225 230 235 240

Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly

245 250 255

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

260 265 270

Leu Ser Val Ser Pro Gly Glu Arg Ala Thr Phe Ser Cys Arg Ala Ser

275 280 285

Gln Ser Ile Gly Thr Asn Ile His Trp Tyr Gln Gln Lys Pro Gly Lys

290 295 300

Pro Pro Arg Leu Leu Ile Lys Tyr Ala Ser Glu Ser Ile Ser Gly Ile

305 310 315 320

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

325 330 335

Ile Ser Ser Val Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln

340 345 350

Asn Asn Asn Trp Pro Thr Thr Phe Gly Cys Gly Thr Lys Leu Thr Val

355 360 365

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

370 375 380

Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn

385 390 395 400

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

405 410 415

Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp

420 425 430

Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr

435 440 445

Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser

450 455 460

Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly

465 470 475 480

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala Leu Thr

485 490 495

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

500 505 510

Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Phe Val Ser Trp

515 520 525

Tyr Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr Asp Val

530 535 540

Ser Asp Arg Pro Ser Gly Val Ser Asp Arg Phe Ser Gly Ser Lys Ser

545 550 555 560

Gly Asn Thr Ala Ser Leu Ile Ile Ser Gly Leu Gln Ala Asp Asp Glu

565 570 575

Ala Asp Tyr Tyr Cys Ser Ser Tyr Gly Ser Ser Ser Thr His Val Ile

580 585 590

Phe Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly

595 600 605

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

610 615 620

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

625 630 635 640

Ser Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Trp Met

645 650 655

Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Asn

660 665 670

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

675 680 685

Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys Asn Ser Leu Tyr Leu Gln

690 695 700

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

705 710 715 720

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

725 730 735

Thr Val Ser Ser

740

<210> 70

<211> 2220

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 70

gaaatcgtta tgacgcagag tccctccacg ctctccgcta gtgtcgggga tcgcgtcatt 60

atcacatgcc aggcctccga gtcaatcagc agctggcttg catggtatca acagaagccg 120

ggaaaagctc ctaaattgct gatctatgaa gcgtcaaaat tggcgtctgg tgtcccatct 180

aggttctccg gctctgggtc tggtgcggaa tttactttga caatctccag tcttcaacca 240

gacgatttcg ctacctacta ctgccaaggg tatttctatt ttataagccg gacatatgta 300

aactccttcg gccaaggaac aaagttgact gttcttggtg gcggaggcag tggtggcggg 360

ggcagcggag gtggtggttc agggggtggt gggagcgaag tccaattggt agaaagtggc 420

ggtggtctgg tgcaacctgg tggatctctt agcctctcat gcgccgctag tggctttact 480

atttcaacta atgcgatgag ctgggttcgc caggcccccg gcaaaggact tgagtgggtc 540

ggcgtcatca ccggcaggga cattacatac tatgcgagtt gggcaaaggg caggttcacg 600

attagccgcg atacttcaaa gaataccgtt taccttcaaa tgaatagctt gagggcggaa 660

gacacagctg tgtattactg cgcgagggat ggaggtagtt ccgccataac ttccaacaac 720

atatggggac aaggcacgct ggttactgtc tcgagtggcg gtggagggtc cggcggtggt 780

ggatcagaaa tcgtccttac acaatctcct agcacactga gtgtgagccc cggcgaacgc 840

gcgactttct cttgcagggc aagtcaatcc atagggacta atatacattg gtatcaacaa 900

aagccaggta aaccacccag gcttttgatt aagtatgcaa gtgagtctat ttccggtatc 960

cctgaccgct tctctggatc aggcagtggc acaagttca cactcaccat atctagtgtg 1020

caatcagagg acttcgccgt gtattactgc caacagaata ataactggcc gactaccttc 1080

ggatgcggta caaagctgac cgttttacgt acggtggctg caccatctgt cttcatcttc 1140

ccgccatctg atgagcagtt gaaatctgga actgcctctg ttgtgtgcct gctgaataac 1200

ttctatccca gagaggccaa agtacagtgg aaggtggata acgccctcca atcgggtaac 1260

tcccaggaga gtgtcacaga gcaggacagc aaggacagca cctacagcct cagcagcacc 1320

ctgacgctga gcaaagcaga ctacgagaaa cacaaagtct acgcctgcga agtcacccat 1380

cagggcctga gctcgcccgt cacaaagagc ttcaacaggg gagagtgtgg cggtggcggt 1440

agcggtggcg gcggaagtgg tggcggagga tcccagtctg ccctgactca gcctgcctcc 1500

gtgtctgggt ctcctggaca gtcgatcacc atctcctgca ctggaaccag cagtgacgtt 1560

ggtggttata actttgtctc ctggtaccaa caacacccag gcaaagcccc caaactcatg 1620

atctatgatg tcagtgatcg gccctcaggg gtgtctgatc gcttctccgg ctccaagtct 1680

ggcaacacgg cctccctgat catctctggc ctccaggctg acgacgaggc tgattattac 1740

tgcagctcat atgggagcag cagcactcat gtgattttcg gcggagggac caaggtgacc 1800

gtcctaggtg gaggcggttc aggcggaggt ggttccggcg gtggcggctc cggtggaggc 1860

ggctctcagg tgcaattgca ggagtcgggg ggaggcctgg tcaagcctgg agggtccctg 1920

agtctctcct gtgcagcctc tggattcacc tttagtagtt attggatgag ctgggtccgc 1980

caggctccag ggaaggggct ggagtgggtg gccaacataa accgcgatgg aagtgcgagt 2040

tactatgtgg actctgtgaa gggccgattc accatctcca gagacgacgc caagaactca 2100

ctgtatctgc aaatgaacag cctgagagct gaggacacgg ctgtgtatta ctgtgcgaga 2160

gatcgtgggg tgggctactt cgatctctgg ggccgtggca ccctggtcac cgtctctagc 2220

<210> 71

<211> 1224

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 71

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

1 5 10 15

Glu Arg Ala Thr Phe Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr Asn

20 25 30

Ile His Trp Tyr Gln Gln Lys Pro Gly Lys Pro Pro Arg Leu Leu Ile

35 40 45

Lys Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Asp Arg Phe Ser Gly

50 55 60

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

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Asn Asn Asn Trp Pro Thr

85 90 95

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

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

115 120 125

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

130 135 140

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

145 150 155 160

Val His Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Leu Gly

165 170 175

Val Ile Trp Ser Gly Gly Asn Thr Asp Tyr Asn Thr Pro Phe Thr Ser

180 185 190

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

195 200 205

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

210 215 220

Ala Leu Thr Tyr Tyr Asp Tyr Glu Phe Ala Tyr Trp Gly Gln Gly Thr

225 230 235 240

Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

245 250 255

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

260 265 270

Thr Leu Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser

275 280 285

Gly Met Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Cys Leu Glu

290 295 300

Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala

305 310 315 320

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

325 330 335

Tyr Leu Gln Met Asn Ser Leu Asp Ala Glu Asp Thr Ala Val Tyr Tyr

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val

420 425 430

Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro

435 440 445

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

450 455 460

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

465 470 475 480

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

485 490 495

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

500 505 510

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

515 520 525

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

530 535 540

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

545 550 555 560

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

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

660 665 670

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

675 680 685

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

690 695 700

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

705 710 715 720

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

725 730 735

Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Gly Tyr Asp Met Cys Trp

740 745 750

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

755 760 765

Ala Gly Ser Ala Gly Ile Thr Tyr Asp Ala Asn Trp Ala Lys Gly Arg

770 775 780

Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met

785 790 795 800

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

805 810 815

Ala Phe Ser Phe Asp Tyr Ala Met Asp Leu Trp Gly Gln Gly Thr Leu

820 825 830

Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

835 840 845

Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser

850 855 860

Pro Ser Thr Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys

865 870 875 880

Gln Ala Ser Gln Ser Ile Ser Ser His Leu Asn Trp Tyr Gln Gln Lys

885 890 895

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

900 905 910

Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe

915 920 925

Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp Phe Ala Thr Tyr Tyr

930 935 940

Cys Gln Gln Gly Tyr Ser Trp Gly Asn Val Asp Asn Val Phe Gly Gly

945 950 955 960

Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly

965 970 975

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

980 985 990

Gly Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Ile Ser Ser

995 1000 1005

Tyr His Met Gln Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

1010 1015 1020

Tyr Ile Gly Thr Ile Ser Ser Gly Gly Asn Val Tyr Tyr Ala Ser

1025 1030 1035

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

1040 1045 1050

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

1055 1060 1065

Val Tyr Tyr Cys Ala Arg Asp Ser Gly Tyr Ser Asp Pro Met Trp

1070 1075 1080

Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser

1085 1090 1095

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

1100 1105 1110

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

1115 1120 1125

Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asn Ile Arg

1130 1135 1140

Thr Tyr Leu Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys

1145 1150 1155

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

1160 1165 1170

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

1175 1180 1185

Ser Asp Leu Glu Pro Gly Asp Ala Ala Thr Tyr Tyr Cys Gln Ser

1190 1195 1200

Thr Tyr Leu Gly Thr Asp Tyr Val Gly Gly Ala Phe Gly Gly Gly

1205 1210 1215

Th Lys Val Glu Ile Lys

1220

<210> 72

<211> 3672

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 72

gaaatcgtcc ttacacaatc tcctagcaca ctgagtgtga gccccggcga acgcgcgact 60

ttctcttgca gggcaagtca atccataggg actaatatac attggtatca acaaaagcca 120

ggtaaaccac ccaggctttt gattaagtat gcaagtgagt ctatttccgg tatccctgac 180

cgcttctctg gatcaggcag tggcacagag ttcacactca ccatatctag tgtgcaatca 240

gaggacttcg ccgtgtatta ctgccaacag aataataact ggccgactac cttcggaccc 300

ggtacaaagc tgaccgtttt aggcggtggc ggtagtgggg gaggcggttc tggcggcgga 360

gggtccggcg gtggaggatc acaagtacag ttgcagcaat ccggtcccgg tctcgtcaaa 420

ccgagtgaga cgcttagtat aacgtgtact gtttcaggct ttagccttac gaactatgga 480

gttcactgga ttcggcaggc acccggcaaa ggtttggaat ggctgggtgt tatttggtca 540

ggtggaaata cagactataa cacccccttt acaagtcggt tcacaattac gaaagataat 600

tccaaaaatc aagtttattt caagttgaga tccgtccgcg cggacgacac tgcgatctac 660

tattgtgcga gggcactgac ctactacgat tacgaatttg cgtattgggg gcaagggact 720

cttgtaacag tctcgagcgg cggtggaggg tccggcggtg gtggatcaca ggtcacattg 780

aaggaatctg gccccggcct tgttcagcca ggacagaccc ttaggctcac ctgtgccttc 840

agtggttttt ctcttagcac tagcggtatg ggggtcggct ggattcggca gcctcccggc 900

aaatgtcttg agtggttggc tcacatttgg tgggacgacg acaaacggta taatcctgcc 960

ttgaaaagtc ggctgaccat tagtaaggat acctcaaaaa atcaagtgta cttgcaaatg 1020

aatagccttg acgccgagga tacggctgta tattattgcg ctcggatgga actctggtct 1080

tactactttg attattgggg gcaggggact ctcgtcacgg tgtcgagtgc tagcaccaag 1140

ggcccatcgg tcttccccct ggcaccctcc tccaagagca cctctggggg cacagcggcc 1200

ctgggctgcc tggtcaagga ctacttcccc gaaccggtga cggtgtcgtg gaactcaggc 1260

gccctgacca gcggcgtgca caccttcccg gctgtcctac agtcctcagg actctactcc 1320

ctcagcagcg tggtgaccgt gccctccagc agcttgggca cccagaccta catctgcaac 1380

gtgaatcaca agcccagcaa caccaaggtg gacaagagag ttgagcccaa atcttgtgac 1440

aaaactcaca catgcccacc gtgcccagca cctgaagccg cgggggcacc gtcagtcttc 1500

ctcttccccc caaaacccaa ggacaccctc atgatctccc ggacccctga ggtcacatgc 1560

gtggtggtgg acgtgagcca cgaagaccct gaggtcaagt tcaactggta cgtggacggc 1620

gtggaggtgc ataatgccaa gacaaagccg cgggaggagc agtacaacag cacgtaccgt 1680

gtggtcagcg tcctcaccgt cctgcaccag gactggctga atggcaagga gtacaagtgc 1740

gcggtctcca acaaagccct cccagccccc atcgagaaaa ccatctccaa agccaaaggg 1800

cagccccgag aaccacaggt gtacaccctg cccccatccc gggatgagct gaccaagaac 1860

caggtcagcc tgacctgcct ggtcaaaggc ttctatccca gcgacatcgc cgtggagtgg 1920

gagagcaatg ggcagccgga gaacaactac aagaccacgc ctcccgtgct ggactccgac 1980

ggctccttct tcctctatag caagctcacc gtggacaaga gcaggtggca gcaggggaac 2040

gtcttctcat gctccgtgat gcatgaggct ctgcacaacc actacacgca gaagagcctc 2100

tccctgtctc cgggtggcgg tggagggtcc ggcggtggtg gatccgaggt gcagctgttg 2160

gagtctgggg gaggcttggt acagcctggg gggtccctga gactctcctg tgcagcctct 2220

ggattctcct tcagtagcgg gtacgacatg tgctgggtcc gccaggctcc agggaagggg 2280

ctggagtgga tcgcatgcat tgctgctggt agtgctggta tcacttacga cgcgaactgg 2340

gcgaaaggcc ggttcaccat ctccagagac aattccaaga acacgctgta tctgcaaatg 2400

aacagcctga gagccgagga cacggccgta tattactgtg cgagatcggc gttttcgttc 2460

gactacgcca tggacctctg gggccaggga accctggtca ccgtgtcgag cggtggaggc 2520

ggatctggcg gaggtggttc cggcggtggc ggctccggtg gaggcggctc tgacatccag 2580

atgacccagt ctccttccac cctgtctgca tctgtaggag acagagtcac catcacttgc 2640

caggccagtc agagcattag ttcccactta aactggtatc agcagaaacc agggaaagcc 2700

cctaagctcc tgatctataa ggcatccact ctggcatctg gggtcccatc aaggttcagc 2760

ggcagtggat ctgggacaga atttactctc accatcagca gcctgcagcc tgatgatttt 2820

gcaacttatt actgccaaca gggttatagt tggggtaatg ttgataatgt tttcggcgga 2880

gggaccaagg tggagatcaa aggcggtgga gggtccggcg gtggtggctc cggacggtcg 2940

ctggtggagt ctgggggagg cttggtccag cctggggggt ccctgagact ctcctgtact 3000

gcctctggat tcaccatcag tagctaccac atgcagtggg tccgccaggc tccagggaag 3060

gggctggagt acatcggaac cattagtagt ggtggtaatg tatactacgc aagctccgct 3120

agaggcagat tcaccatctc cagaccctcg tccaagaaca cggtggatct tcaaatgaac 3180

agcctgagag ccgaggacac ggctgtgtat tactgtgcga gagactctgg ttatagtgat 3240

cctatgtggg gccagggaac cctggtcacc gtctcttcag gcggtggcgg tagtggggga 3300

ggcggttctg gcggcggagg gtccggcggt ggagatcag acgttgtgat gacccagtct 3360

ccatcttccg tgtctgcatc tgtaggagac agagtcacca tcacctgtca ggccagtcag 3420

aacattagga cttacttatc ctggtatcag cagaaaccag ggaaagcccc taagctcctg 3480

atctatgctg cagccaatct ggcatctggg gtcccatcaa ggttcagcgg cagtggatct 3540

gggacagatt tcactctcac catcagcgac ctggagcctg gcgatgctgc aacttactat 3600

tgtcagtcta cctatcttgg tactgattat gttggcggtg ctttcggcgg agggaccaag 3660

gtggagatca aa 3672

<210> 73

<211> 739

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 73

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

1 5 10 15

Asp Arg Val Ile Ile Thr Cys Gln Ala Ser Glu Ser Ile Ser Ser Trp

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gly Tyr Phe Tyr Phe Ile Ser

85 90 95

Arg Thr Tyr Val Asn Ser Phe Gly Gln Gly Thr Lys Leu Thr Val Leu

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

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

130 135 140

Gln Pro Gly Gly Ser Leu Ser Leu Ser Cys Ala Ala Ser Gly Phe Thr

145 150 155 160

Ile Ser Thr Asn Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly

165 170 175

Leu Glu Trp Val Gly Val Ile Thr Gly Arg Asp Ile Thr Tyr Tyr Ala

180 185 190

Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Arg Asp Thr Ser Lys Asn

195 200 205

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

210 215 220

Tyr Tyr Cys Ala Arg Asp Gly Gly Ser Ser Ala Ile Thr Ser Asn Asn

225 230 235 240

Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly

245 250 255

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

260 265 270

Leu Ser Ala Ser Pro Gly Glu Arg Val Thr Ile Thr Cys Ser Ala Ser

275 280 285

Ser Ser Val Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Gln Ala

290 295 300

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

305 310 315 320

Ser Arg Phe Ser Gly Ser Gly Ser Gly Asn Asp His Thr Leu Thr Ile

325 330 335

Ser Ser Met Glu Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly

340 345 350

Ser Val Tyr Pro Phe Thr Phe Gly Cys Gly Thr Lys Val Glu Ile Lys

355 360 365

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

370 375 380

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

385 390 395 400

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

405 410 415

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

420 425 430

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

435 440 445

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

450 455 460

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser

465 470 475 480

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala Leu Thr Gln

485 490 495

Pro Ala Ser Val Ser Gly Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys

500 505 510

Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Phe Val Ser Trp Tyr

515 520 525

Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr Asp Val Ser

530 535 540

Asp Arg Pro Ser Gly Val Ser Asp Arg Phe Ser Gly Ser Lys Ser Gly

545 550 555 560

Asn Thr Ala Ser Leu Ile Ile Ser Gly Leu Gln Ala Asp Asp Glu Ala

565 570 575

Asp Tyr Tyr Cys Ser Ser Tyr Gly Ser Ser Ser Thr His Val Ile Phe

580 585 590

Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly Gly

595 600 605

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln

610 615 620

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

625 630 635 640

Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Trp Met Ser

645 650 655

Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Asn Ile

660 665 670

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

675 680 685

Phe Thr Ile Ser Arg Asp Asp Ala Lys Asn Ser Leu Tyr Leu Gln Met

690 695 700

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

705 710 715 720

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

725 730 735

Val Ser Ser

<210> 74

<211> 2217

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 74

gaaatcgtta tgacgcagag tccctccacg ctctccgcta gtgtcgggga tcgcgtcatt 60

atcacatgcc aggcctccga gtcaatcagc agctggcttg catggtatca acagaagccg 120

ggaaaagctc ctaaattgct gatctatgaa gcgtcaaaat tggcgtctgg tgtcccatct 180

aggttctccg gctctgggtc tggtgcggaa tttactttga caatctccag tcttcaacca 240

gacgatttcg ctacctacta ctgccaaggg tatttctatt ttataagccg gacatatgta 300

aactccttcg gccaaggaac aaagttgact gttcttggtg gcggaggcag tggtggcggg 360

ggcagcggag gtggtggttc agggggtggt gggagcgaag tccaattggt agaaagtggc 420

ggtggtctgg tgcaacctgg tggatctctt agcctctcat gcgccgctag tggctttact 480

atttcaacta atgcgatgag ctgggttcgc caggcccccg gcaaaggact tgagtgggtc 540

ggcgtcatca ccggcaggga cattacatac tatgcgagtt gggcaaaggg caggttcacg 600

attagccgcg atacttcaaa gaataccgtt taccttcaaa tgaatagctt gagggcggaa 660

gacacagctg tgtattactg cgcgagggat ggaggtagtt ccgccataac ttccaacaac 720

atatggggac aaggcacgct ggttactgtc tcgagcggcg gtggagggtc cggcggtggt 780

ggatcagaaa atgtattgac acagagcccc gcctccctca gtgcctcacc tggggaaagg 840

gtaactatca cttgctctgc atcaagcagc gtctcataca tgcattggta tcaacaaaag 900

cctggacagg cccccaagct ctggatatac gatacgagca agctggcttc cggcgtacct 960

agccgcttca gtggttccgg ctcaggcaac gatcacaccc ttacgatttc cagtatggaa 1020

cccgaagatt ttgcaactta ttattgtttc caggggagcg tgtacccatt cactttcggg 1080

tgtgggacaa aagtggagat caagcgtacg gtggctgcac catctgtctt catcttcccg 1140

ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 1200

tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 1260

caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 1320

acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 1380

ggcctgagct cgcccgtcac aaagagcttc aacagggag agtgtggcgg tggcggtagc 1440

ggtggcggcg gaagtggtgg cggaggatcc cagtctgccc tgactcagcc tgcctccgtg 1500

tctgggtctc ctggacagtc gatcaccatc tcctgcactg gaaccagcag tgacgttggt 1560

ggttataact ttgtctcctg gtaccaacaa cacccaggca aagcccccaa actcatgatc 1620

tatgatgtca gtgatcggcc ctcaggggtg tctgatcgct tctccggctc caagtctggc 1680

aacacggcct ccctgatcat ctctggcctc caggctgacg acgaggctga ttattactgc 1740

agctcatatg ggagcagcag cactcatgtg attttcggcg gagggaccaa ggtgaccgtc 1800

ctaggtggag gcggttcagg cggaggtggt tccggcggtg gcggctccgg tggaggcggc 1860

tctcaggtgc aattgcagga gtcgggggga ggcctggtca agcctggagg gtccctgagt 1920

ctctcctgtg cagcctctgg attcaccttt agtagttatt ggatgagctg ggtccgccag 1980

gctccaggga aggggctgga gtgggtggcc aacataaacc gcgatggaag tgcgagttac 2040

tatgtggact ctgtgaaggg ccgattcacc atctccagag acgacgccaa gaactcactg 2100

tatctgcaaa tgaacagcct gagagctgag gacacggctg tgtattactg tgcgagagat 2160

cgtggggtgg gctacttcga tctctggggc cgtggcaccc tggtcaccgt ctctagc 2217

<210> 75

<211> 1234

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 75

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

1 5 10 15

Glu Arg Ala Thr Phe Ser Cys Arg Ala Ser Gln Ser Ile Gly Thr Asn

20 25 30

Ile His Trp Tyr Gln Gln Lys Pro Gly Lys Pro Pro Arg Leu Leu Ile

35 40 45

Lys Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Asp Arg Phe Ser Gly

50 55 60

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

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Asn Asn Asn Trp Pro Thr

85 90 95

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

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln

115 120 125

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

130 135 140

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

145 150 155 160

Val His Trp Ile Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Leu Gly

165 170 175

Val Ile Trp Ser Gly Gly Asn Thr Asp Tyr Asn Thr Pro Phe Thr Ser

180 185 190

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

195 200 205

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

210 215 220

Ala Leu Thr Tyr Tyr Asp Tyr Glu Phe Ala Tyr Trp Gly Gln Gly Thr

225 230 235 240

Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

245 250 255

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

260 265 270

Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys

275 280 285

Ala Ala Ser Gly Phe Thr Ile Ser Thr Asn Ala Met Ser Trp Val Arg

290 295 300

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

305 310 315 320

Asp Ile Thr Tyr Tyr Ala Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser

325 330 335

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

340 345 350

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

355 360 365

Ala Ile Thr Ser Asn Asn Ile Trp Gly Gln Gly Thr Leu Val Thr Val

370 375 380

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

385 390 395 400

Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys

405 410 415

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

420 425 430

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

435 440 445

Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr

450 455 460

Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val

465 470 475 480

Asp Lys Arg Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro

485 490 495

Pro Cys Pro Ala Pro Glu Ala Ala Gly Ala Pro Ser Val Phe Leu Phe

500 505 510

Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val

515 520 525

Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe

530 535 540

Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro

545 550 555 560

Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr

565 570 575

Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Ala Val

580 585 590

Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

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

660 665 670

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

675 680 685

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

690 695 700

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

705 710 715 720

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

725 730 735

Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe

740 745 750

Ser Phe Ser Ser Gly Tyr Asp Met Cys Trp Val Arg Gln Ala Pro Gly

755 760 765

Lys Gly Leu Glu Trp Ile Ala Cys Ile Ala Ala Gly Ser Ala Gly Ile

770 775 780

Thr Tyr Asp Ala Asn Trp Ala Lys Gly Arg Phe Thr Ile Ser Arg Asp

785 790 795 800

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

805 810 815

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

820 825 830

Ala Met Asp Leu Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly

835 840 845

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly

850 855 860

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

865 870 875 880

Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile

885 890 895

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

900 905 910

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

915 920 925

Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser

930 935 940

Leu Gln Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser

945 950 955 960

Trp Gly Asn Val Asp Asn Val Phe Gly Gly Gly Thr Lys Val Glu Ile

965 970 975

Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Arg Ser Leu Val

980 985 990

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

995 1000 1005

Cys Thr Ala Ser Gly Phe Thr Ile Ser Ser Tyr His Met Gln Trp

1010 1015 1020

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

1025 1030 1035

Ser Ser Gly Gly Asn Val Tyr Tyr Ala Ser Ser Ala Arg Gly Arg

1040 1045 1050

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

1055 1060 1065

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

1070 1075 1080

Arg Asp Ser Gly Tyr Ser Asp Pro Met Trp Gly Gln Gly Thr Leu

1085 1090 1095

Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

1100 1105 1110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Val Val Met Thr

1115 1120 1125

Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly Asp Arg Val Thr

1130 1135 1140

Ile Thr Cys Gln Ala Ser Gln Asn Ile Arg Thr Tyr Leu Ser Trp

1145 1150 1155

Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala

1160 1165 1170

Ala Ala Asn Leu Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser

1175 1180 1185

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asp Leu Glu Pro

1190 1195 1200

Gly Asp Ala Ala Thr Tyr Tyr Cys Gln Ser Thr Tyr Leu Gly Thr

1205 1210 1215

Asp Tyr Val Gly Gly Ala Phe Gly Gly Gly Thr Lys Val Glu Ile

1220 1225 1230

Lys

<210> 76

<211> 3702

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 76

gaaatcgtcc ttacacaatc tcctagcaca ctgagtgtga gccccggcga acgcgcgact 60

ttctcttgca gggcaagtca atccataggg actaatatac attggtatca acaaaagcca 120

ggtaaaccac ccaggctttt gattaagtat gcaagtgagt ctatttccgg tatccctgac 180

cgcttctctg gatcaggcag tggcacagag ttcacactca ccatatctag tgtgcaatca 240

gaggacttcg ccgtgtatta ctgccaacag aataataact ggccgactac cttcggaccc 300

ggtacaaagc tgaccgtttt aggcggtggc ggtagtgggg gaggcggttc tggcggcgga 360

gggtccggcg gtggaggatc acaagtacag ttgcagcaat ccggtcccgg tctcgtcaaa 420

ccgagtgaga cgcttagtat aacgtgtact gtttcaggct ttagccttac gaactatgga 480

gttcactgga ttcggcaggc acccggcaaa ggtttggaat ggctgggtgt tatttggtca 540

ggtggaaata cagactataa cacccccttt acaagtcggt tcacaattac gaaagataat 600

tccaaaaatc aagtttattt caagttgaga tccgtccgcg cggacgacac tgcgatctac 660

tattgtgcga gggcactgac ctactacgat tacgaatttg cgtattgggg gcaagggact 720

cttgtaacag tctcgagcgg tggaggcgga tctggcggag gtggttccgg cggtggcggc 780

tccggtggag gcggctctga ggtgcagctg gtggagtctg ggggaggctt ggtccagcct 840

ggggggtccc tgagactctc ctgtgcagcc tctggattca ccatcagtac caatgcaatg 900

agctgggtcc gccaggctcc agggaagtgt ctggagtgga tcggagtcat tactggtcgt 960

gatatcacat actacgcgag ctgggcgaaa ggcagattca ccatctccag agacaattcc 1020

aagaacacgc tgtatcttca aatgaacagc ctgagagccg aggacacggc tgtgtattac 1080

tgtgcgagag acggtggttc ttctgctatt actagtaaca acatttgggg ccagggaacc 1140

ctggtcaccg tgtcctcagc tagcaccaag ggcccatcgg tcttccccct ggcaccctcc 1200

tccaagagca cctctggggg cacagcggcc ctgggctgcc tggtcaagga ctacttcccc 1260

gaaccggtga cggtgtcgtg gaactcaggc gccctgacca gcggcgtgca caccttcccg 1320

gctgtcctac agtcctcagg actctactcc ctcagcagcg tggtgaccgt gccctccagc 1380

agcttgggca cccagaccta catctgcaac gtgaatcaca agcccagcaa caccaaggtg 1440

gacaagagag ttgagcccaa atcttgtgac aaaactcaca catgcccacc gtgcccagca 1500

cctgaagccg cggggggcacc gtcagtcttc ctcttccccc caaaacccaa ggacaccctc 1560

atgatctccc ggacccctga ggtcacatgc gtggtggtgg acgtgagcca cgaagaccct 1620

gaggtcaagt tcaactggta cgtggacggc gtggaggtgc ataatgccaa gacaaagccg 1680

cgggaggagc agtacaacag cacgtaccgt gtggtcagcg tcctcaccgt cctgcaccag 1740

gactggctga atggcaagga gtacaagtgc gcggtctcca acaaagccct cccagccccc 1800

atcgagaaaa ccatctccaa agccaaaggg cagccccgag aaccacaggt gtacaccctg 1860

cccccatccc gggatgagct gaccaagaac caggtcagcc tgacctgcct ggtcaaaggc 1920

ttctatccca gcgacatcgc cgtggagtgg gagagcaatg ggcagccgga gaacaactac 1980

aagaccacgc ctcccgtgct ggactccgac ggctccttct tcctctatag caagctcacc 2040

gtggacaaga gcaggtggca gcaggggaac gtcttctcat gctccgtgat gcatgaggct 2100

ctgcacaacc actacacgca gaagagcctc tccctgtctc cgggtggcgg tggagggtcc 2160

ggcggtggtg gatccgaggt gcagctgttg gagtctgggg gaggcttggt acagcctggg 2220

gggtccctga gactctcctg tgcagcctct ggattctcct tcagtagcgg gtacgacatg 2280

tgctgggtcc gccaggctcc agggaagggg ctggagtgga tcgcatgcat tgctgctggt 2340

agtgctggta tcacttacga cgcgaactgg gcgaaaggcc ggttcaccat ctccagagac 2400

aattccaaga acacgctgta tctgcaaatg aacagcctga gagccgagga cacggccgta 2460

tattactgtg cgagatcggc gttttcgttc gactacgcca tggacctctg gggccaggga 2520

accctggtca ccgtgtcgag cggtggaggc ggatctggcg gaggtggttc cggcggtggc 2580

ggctccggtg gaggcggctc tgacatccag atgacccagt ctccttccac cctgtctgca 2640

tctgtaggag acagagtcac catcacttgc caggccagtc agagcattag ttcccactta 2700

aactggtatc agcagaaacc agggaaagcc cctaagctcc tgatctataa ggcatccact 2760

ctggcatctg gggtcccatc aaggttcagc ggcagtggat ctgggacaga atttactctc 2820

accatcagca gcctgcagcc tgatgatttt gcaacttatt actgccaaca gggttatagt 2880

tggggtaatg ttgataatgt tttcggcgga gggaccaagg tggagatcaa aggcggtgga 2940

gggtccggcg gtggtggctc cggacggtcg ctggtggagt ctgggggagg cttggtccag 3000

cctggggggt ccctgagact ctcctgtact gcctctggat tcaccatcag tagctaccac 3060

atgcagtggg tccgccaggc tccagggaag gggctggagt acatcggaac cattagtagt 3120

ggtggtaatg tatactacgc aagctccgct agaggcagat tcaccatctc cagaccctcg 3180

tccaagaaca cggtggatct tcaaatgaac agcctgagag ccgaggacac ggctgtgtat 3240

tactgtgcga gagactctgg ttatagtgat cctatgtggg gccagggaac cctggtcacc 3300

gtctcttcag gcggtggcgg tagtggggga ggcggttctg gcggcggagg gtccggcggt 3360

ggaggatcag acgttgtgat gacccagtct ccatcttccg tgtctgcatc tgtaggagac 3420

agagtcacca tcacctgtca ggccagtcag aacattagga cttacttatc ctggtatcag 3480

cagaaaccag ggaaagcccc taagctcctg atctatgctg cagccaatct ggcatctggg 3540

gtcccatcaa ggttcagcgg cagtggatct gggacagatt tcactctcac catcagcgac 3600

ctggagcctg gcgatgctgc aacttactat tgtcagtcta cctatcttgg tactgattat 3660

gttggcggtg ctttcggcgg agggaccaag gtggagatca aa 3702

<210> 77

<211> 739

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 77

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Ser Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

245 250 255

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

260 265 270

Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Glu Ser Ile Ser Ser Trp

275 280 285

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

290 295 300

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

305 310 315 320

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

325 330 335

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gly Tyr Phe Tyr Phe Ile Ser

340 345 350

Arg Thr Tyr Val Asn Ser Phe Gly Cys Gly Thr Lys Val Glu Ile Lys

355 360 365

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

370 375 380

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

385 390 395 400

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

405 410 415

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

420 425 430

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

435 440 445

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

450 455 460

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys Gly Gly Gly Gly Ser

465 470 475 480

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Ser Ala Leu Thr Gln

485 490 495

Pro Ala Ser Val Ser Gly Ser Pro Gly Gln Ser Ile Thr Ile Ser Cys

500 505 510

Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr Asn Phe Val Ser Trp Tyr

515 520 525

Gln Gln His Pro Gly Lys Ala Pro Lys Leu Met Ile Tyr Asp Val Ser

530 535 540

Asp Arg Pro Ser Gly Val Ser Asp Arg Phe Ser Gly Ser Lys Ser Gly

545 550 555 560

Asn Thr Ala Ser Leu Ile Ile Ser Gly Leu Gln Ala Asp Asp Glu Ala

565 570 575

Asp Tyr Tyr Cys Ser Ser Tyr Gly Ser Ser Ser Thr His Val Ile Phe

580 585 590

Gly Gly Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly Gly

595 600 605

Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln

610 615 620

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

625 630 635 640

Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Trp Met Ser

645 650 655

Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Asn Ile

660 665 670

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

675 680 685

Phe Thr Ile Ser Arg Asp Asp Ala Lys Asn Ser Leu Tyr Leu Gln Met

690 695 700

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

705 710 715 720

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

725 730 735

Val Ser Ser

<210> 78

<211> 2220

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 78

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaagtga ccgtcctagg cggtggcggt agtgggggag gcggttctgg cggcggaggg 360

tccggcggtg gaggatcaca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttagcctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg ctcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagtgg cggtggaggg tccggcggtg gtggatcaga cgtcgtgatg 780

acccagtctc cttccaccct gtctgcatct gtaggagaca gagtcaccat caattgccaa 840

gccagtgaga gcattagcag ttggttagcc tggtatcagc agaaaccagg gaaagcccct 900

aagctcctga tctatgaagc atccaaactg gcatctgggg tcccatcaag gttcagcggc 960

agtggatctg ggacagaatt tactctcacc atcagcagcc tgcagcctga tgattttgca 1020

acttattact gccaaggcta tttttatttt attagtcgta cttatgtaaa ttctttcggc 1080

tgtgggacca aggtggagat caaacgtacg gtggctgcac catctgtctt catcttcccg 1140

ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 1200

tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 1260

caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 1320

acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 1380

ggcctgagct cgcccgtcac aaagagcttc aacagggag agtgtggcgg tggcggtagc 1440

ggtggcggcg gaagtggtgg cggaggatcc cagtctgccc tgactcagcc tgcctccgtg 1500

tctgggtctc ctggacagtc gatcaccatc tcctgcactg gaaccagcag tgacgttggt 1560

ggttataact ttgtctcctg gtaccaacaa cacccaggca aagcccccaa actcatgatc 1620

tatgatgtca gtgatcggcc ctcaggggtg tctgatcgct tctccggctc caagtctggc 1680

aacacggcct ccctgatcat ctctggcctc caggctgacg acgaggctga ttattactgc 1740

agctcatatg ggagcagcag cactcatgtg attttcggcg gagggaccaa ggtgaccgtc 1800

ctaggtggag gcggttcagg cggaggtggt tccggcggtg gcggctccgg tggaggcggc 1860

tctcaggtgc aattgcagga gtcgggggga ggcctggtca agcctggagg gtccctgagt 1920

ctctcctgtg cagcctctgg attcaccttt agtagttatt ggatgagctg ggtccgccag 1980

gctccaggga aggggctgga gtgggtggcc aacataaacc gcgatggaag tgcgagttac 2040

tatgtggact ctgtgaaggg ccgattcacc atctccagag acgacgccaa gaactcactg 2100

tatctgcaaa tgaacagcct gagagctgag gacacggctg tgtattactg tgcgagagat 2160

cgtggggtgg gctacttcga tctctggggc cgtggcaccc tggtcaccgt ctctagctga 2220

<210> 79

<211> 1230

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 79

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

1 5 10 15

Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Glu Ser Ile Ser Ser Trp

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gly Tyr Phe Tyr Phe Ile Ser

85 90 95

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

100 105 110

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly

115 120 125

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

130 135 140

Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr

145 150 155 160

Ile Ser Thr Asn Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly

165 170 175

Leu Glu Trp Ile Gly Val Ile Thr Gly Arg Asp Ile Thr Tyr Tyr Ala

180 185 190

Ser Trp Ala Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn

195 200 205

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

210 215 220

Tyr Tyr Cys Ala Arg Asp Gly Gly Ser Ser Ala Ile Thr Ser Asn Asn

225 230 235 240

Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly

245 250 255

Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu

260 265 270

Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly

275 280 285

Tyr Ser Phe Ser Ser Ser Trp Ile Gly Trp Val Arg Gln Ala Pro Gly

290 295 300

Lys Gly Leu Glu Trp Met Gly Ile Ile Tyr Pro Asp Asp Ser Asp Thr

305 310 315 320

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

325 330 335

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

340 345 350

Thr Ala Met Tyr Tyr Cys Ala Arg His Val Thr Met Ile Trp Gly Val

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly

420 425 430

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

435 440 445

Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr

450 455 460

Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg

465 470 475 480

Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro

485 490 495

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

500 505 510

Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val

515 520 525

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

530 535 540

Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu

545 550 555 560

Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His

565 570 575

Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Ala Val Ser Asn Lys

580 585 590

Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln

595 600 605

Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu

610 615 620

Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro

625 630 635 640

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

645 650 655

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

660 665 670

Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val

675 680 685

Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln

690 695 700

Lys Ser Leu Ser Leu Ser Pro Gly Gly Gly Gly Gly Ser Gly Gly Gly

705 710 715 720

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

725 730 735

Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser

740 745 750

Ser Gly Tyr Asp Met Cys Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

755 760 765

Glu Trp Ile Ala Cys Ile Ala Ala Gly Ser Ala Gly Ile Thr Tyr Asp

770 775 780

Ala Asn Trp Ala Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys

785 790 795 800

Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala

805 810 815

Val Tyr Tyr Cys Ala Arg Ser Ala Phe Ser Phe Asp Tyr Ala Met Asp

820 825 830

Leu Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly

835 840 845

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

850 855 860

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

865 870 875 880

Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Ser Ile Ser Ser His

885 890 895

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

900 905 910

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

915 920 925

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

930 935 940

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Gly Tyr Ser Trp Gly Asn

945 950 955 960

Val Asp Asn Val Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Gly Gly

965 970 975

Gly Gly Ser Gly Gly Gly Gly Ser Arg Ser Leu Val Glu Ser Gly Gly

980 985 990

Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Thr Ala Ser

995 1000 1005

Gly Phe Thr Ile Ser Ser Tyr His Met Gln Trp Val Arg Gln Ala

1010 1015 1020

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

1025 1030 1035

Asn Val Tyr Tyr Ala Ser Ser Ala Arg Gly Arg Phe Thr Ile Ser

1040 1045 1050

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

1055 1060 1065

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

1070 1075 1080

Tyr Ser Asp Pro Met Trp Gly Gln Gly Thr Leu Val Thr Val Ser

1085 1090 1095

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

1100 1105 1110

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

1115 1120 1125

Ser Val Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Gln

1130 1135 1140

Ala Ser Gln Asn Ile Arg Thr Tyr Leu Ser Trp Tyr Gln Gln Lys

1145 1150 1155

Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ala Asn Leu

1160 1165 1170

Ala Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr

1175 1180 1185

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

1190 1195 1200

Thr Tyr Tyr Cys Gln Ser Thr Tyr Leu Gly Thr Asp Tyr Val Gly

1205 1210 1215

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

1220 1225 1230

<210> 80

<211> 3690

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 80

gacgtcgtga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60

atcaattgcc aagccagtga gagcattagc agttggttag cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgaa gcatccaaac tggcatctgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagag ttcactctca ccatcagcag cctgcagcct 240

gatgattttg caacttatta ctgccaaggc tatttttatt ttattagtcg tacttatgta 300

aattctttcg gcggagggac caaggtggag atcaaaggcg gtggcggtag tgggggaggc 360

ggttctggcg gcggagggtc cggcggtgga ggatcagagg tgcagctggt ggagtctggg 420

ggaggcttgg tccagcctgg ggggtccctg agactctcct gtgcagcctc tggattcacc 480

atcagtacca atgcaatgag ctgggtccgc caggctccag ggaaggggct ggagtggatc 540

ggagtcatta ctggtcgtga tatcacatac tacgcgagct gggcgaaagg cagattcacc 600

atctccagag acaattccaa gaacacgctg tatcttcaaa tgaacagcct gagagccgag 660

gacacggctg tgtattactg tgcgcgcgac ggtggatcat ctgctattac tagtaacaac 720

atttggggcc aaggaactct ggtcaccgtt tcttcaggcg gtggagggtc cggcggtggt 780

ggatccgagg tgcagctggt gcagtctgga gcagaggtga agaaaccagg agagtctctg 840

aagatctcct gtaagggttc tggatacagc tttagcagtt catggatcgg ctgggtgcgc 900

caggcacctg ggaaaggcct ggaatggatg gggatcatct atcctgatga ctctgatacc 960

agatacagtc catccttcca aggccaggtc accatctcag ccgacaagtc catcaggact 1020

gcctacctgc agtggagtag cctgaaggcc tcggacaccg ctatgtatta ctgtgcgaga 1080

catgttacta tgatttgggg agttattatt gacttctggg gccagggaac cctggtcacc 1140

gtctcctcag ctagcaccaa gggcccatcg gtcttccccc tggcaccctc ctccaagagc 1200

acctctgggg gcacagcggc cctgggctgc ctggtcaagg actacttccc cgaaccggtg 1260

acggtgtcgt ggaactcagg cgccctgacc agcggcgtgc acaccttccc ggctgtccta 1320

cagtcctcag gactctactc cctcagcagc gtggtgaccg tgccctccag cagcttgggc 1380

acccagacct acatctgcaa cgtgaatcac aagcccagca acaccaaggt ggacaagaga 1440

gttgagccca aatcttgtga caaaactcac acatgcccac cgtgcccagc acctgaagcc 1500

gcggggggcac cgtcagtctt cctcttcccc ccaaaaccca aggacaccct catgatctcc 1560

cggacccctg aggtcacatg cgtggtggtg gacgtgagcc acgaagaccc tgaggtcaag 1620

ttcaactggt acgtggacgg cgtggaggtg cataatgcca agacaaagcc gcgggaggag 1680

cagtacaaca gcacgtaccg tgtggtcagc gtcctcaccg tcctgcacca ggactggctg 1740

aatggcaagg agtacaagtg cgcggtctcc aacaaagccc tcccagcccc catcgagaaa 1800

accatctcca aagccaaagg gcagccccga gaaccacagg tgtataccct gcccccatcc 1860

cgggatgagc tgaccaagaa ccaggtcagc ctgacctgcc tggtcaaagg cttctatccc 1920

agcgacatcg ccgtggagtg ggagagcaat gggcagccgg agaacaacta caagaccacg 1980

cctcccgtgc tggactccga cggctccttc ttcctctata gcaagctcac cgtggacaag 2040

agcaggtggc agcaggggaa cgtcttctca tgctccgtga tgcatgaggc tctgcacaac 2100

cactacacgc agaagagcct ctccctgtct ccgggtggcg gtggagggtc cggcggtggt 2160

ggatccgagg tgcagctgtt ggagtctggg ggaggcttgg tacagcctgg ggggtccctg 2220

agactctcct gtgcagcctc tggattctcc ttcagtagcg ggtacgacat gtgctgggtc 2280

cgccaggctc cagggaaggg gctggagtgg atcgcatgca ttgctgctgg tagtgctggt 2340

atcacttacg acgcgaactg ggcgaaaggc cggttcacca tctccagaga caattccaag 2400

aacacgctgt atctgcaaat gaacagcctg agagccgagg acacggccgt atattactgt 2460

gcgagatcgg cgttttcgtt cgactacgcc atggacctct ggggccaggg aaccctggtc 2520

accgtctcga gcggtggagg cggatctggc ggaggtggtt ccggcggtgg cggctccggt 2580

ggaggcggct ctgacatcca gatgacccag tctccttcca ccctgtctgc atctgtagga 2640

gacagagtca ccatcacttg ccaggccagt cagagcatta gttcccactt aaactggtat 2700

cagcagaaac cagggaaagc ccctaagctc ctgatctata aggcatccac tctggcatct 2760

ggggtcccat caaggttcag cggcagtgga tctgggacag aatttactct caccatcagc 2820

agcctgcagc ctgatgattt tgcaacttat tactgccaac agggttatag ttggggtaat 2880

gttgataatg ttttcggcgg agggaccaag gtggagatca aaggcggtgg agggtccggc 2940

ggtggtggat cccggtcgct ggtggagtct gggggaggct tggtccagcc tggggggtcc 3000

ctgagactct cctgtacagc ctctggattc accatcagta gctaccacat gcagtgggtc 3060

cgccaggctc cagggaaggg gctggagtac atcggaacca ttagtagtgg tggtaatgta 3120

tactacgcga gctccgcgag aggcagattc accatctcca gaccctcgtc caagaacacg 3180

gtggatcttc aaatgaacag cctgagagcc gaggacacgg ctgtgtatta ctgtgcgaga 3240

gactctggtt atagtgatcc tatgtggggc cagggaaccc tggtcaccgt ctcgagcggc 3300

ggtggcggta gtgggggagg cggttctggc ggcggagggt ccggcggtgg aggatcagac 3360

gttgtgatga cccagtctcc atcttccgtg tctgcatctg taggagacag agtcaccatc 3420

acctgtcagg ccagtcagaa cattaggact tacttatcct ggtatcagca gaaaccaggg 3480

aaagccccta agctcctgat ctatgctgca gccaatctgg catctggggt cccatcaagg 3540

ttcagcggca gtggatctgg gacagatttc actctcacca tcagcgacct ggagcctggc 3600

gatgctgcaa cttactattg tcagtctacc tatcttggta ctgattatgt tggcggtgct 3660

ttcggcggag ggaccaaggt ggagatcaaa 3690

<210> 81

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 81

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Ala

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Phe Asn Ser Tyr Pro Phe

85 90 95

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

100 105 110

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

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

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

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

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

<210> 82

<211> 642

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 82

gccatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gggcattagc agtgctttag cctggtatca gcagaaacca 120

gggaaagctc ctaagctcct gatctatgat gcctccagtt tggaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagatttg caacttatta ctgtcaacag tttaatagtt acccattcac tttcggccct 300

gggaccaaag tggatatcaa acgtacggtg 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 ccatcagggc 600

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 642

<210> 83

<211> 450

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 83

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

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Ser Ser Ser

20 25 30

Trp Ile Gly Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Asp Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Arg Thr Ala Tyr

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

165 170 175

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

180 185 190

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

195 200 205

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

210 215 220

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

225 230 235 240

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

245 250 255

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

260 265 270

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

275 280 285

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

290 295 300

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

305 310 315 320

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

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

Asp Lys Ser Arg Trp Gln Gln 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

Pro Gly

450

<210> 84

<211> 1350

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 84

gaggtgcagc tggtgcagtc tggagcagag gtgaagaaac caggagagtc tctgaagatc 60

tcctgtaagg gttctggata cagctttagc agttcatgga tcggctgggt gcgccaggca 120

cctgggaaag gcctggaatg gatggggatc atctatcctg atgactctga taccagatac 180

agtccatcct tccaaggcca ggtcaccatc tcagccgaca agtccatcag gactgcctac 240

ctgcagtgga gtagcctgaa ggcctcggac accgctatgt attactgtgc gagacatgtt 300

actatgattt ggggagttat tattgacttc tggggccagg gaaccctggt caccgtctcc 360

tcagctagca 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 gagagttgag 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 tcccagcgac 1140

atcgccgtgg agtgggagag caatgggcag ccggagaaca actacaagac cacgcctccc 1200

gtgctggact ccgacggctc cttcttcctc tatagcaagc tcaccgtgga caagagcagg 1260

tggcagcagg ggaacgtctt ctcatgctcc gtgatgcatg aggctctgca caaccactac 1320

acgcagaaga gcctctccct gtctccggggt 1350

<210> 85

<211> 214

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 85

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Ala

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Phe Asn Ser Tyr Pro Phe

85 90 95

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

100 105 110

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

115 120 125

Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala

130 135 140

Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln

145 150 155 160

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

165 170 175

Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr

180 185 190

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

<210> 86

<211> 642

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 86

gccatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gggcattagc agtgctttag cctggtatca gcagaaacca 120

gggaaagctc ctaagctcct gatctatgat gcctccagtt tggaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagatttg caacttatta ctgtcaacag tttaatagtt acccattcac tttcggccct 300

gggaccaaag tggatatcaa acgtacggtg 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 ccatcagggc 600

ctgagctcgc ccgtcacaaa gagcttcaac aggggagagt gt 642

<210> 87

<211> 1225

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 87

Gln Ile Val Leu Ser Gln Ser Pro Ala Ile Leu Ser Ala Ser Pro Gly

1 5 10 15

Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Ile

20 25 30

His Trp Phe Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr

35 40 45

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser

50 55 60

Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu

65 70 75 80

Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr

85 90 95

Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Asn Met

145 150 155 160

His Trp Val Lys Gln Thr Pro Gly Arg Gly Leu Glu Trp Ile Gly Ala

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly Ala Gly

225 230 235 240

Thr Thr Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

245 250 255

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

260 265 270

Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Ile Ser Thr

275 280 285

Asn Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp

290 295 300

Ile Gly Val Ile Thr Gly Arg Asp Ile Thr Tyr Tyr Ala Ser Trp Ala

305 310 315 320

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr

325 330 335

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

340 345 350

Ala Arg Asp Gly Gly Ser Ser Ala Ile Thr Ser Asn Asn Ile Trp Gly

355 360 365

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

370 375 380

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

385 390 395 400

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

405 410 415

Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala

420 425 430

Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val

435 440 445

Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His

450 455 460

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

465 470 475 480

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly

485 490 495

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

500 505 510

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

515 520 525

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

530 535 540

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

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

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

660 665 670

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

675 680 685

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

690 695 700

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

705 710 715 720

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

725 730 735

Ser Cys Ala Ala Ser Gly Phe Ser Phe Ser Ser Gly Tyr Asp Met Cys

740 745 750

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

755 760 765

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

770 775 780

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

785 790 795 800

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

805 810 815

Ser Ala Phe Ser Phe Asp Tyr Ala Met Asp Leu Trp Gly Gln Gly Thr

820 825 830

Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

835 840 845

Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln

850 855 860

Ser Pro Ser Thr Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr

865 870 875 880

Cys Gln Ala Ser Gln Ser Ile Ser Ser His Leu Asn Trp Tyr Gln Gln

885 890 895

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

900 905 910

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

915 920 925

Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp Phe Ala Thr Tyr

930 935 940

Tyr Cys Gln Gln Gly Tyr Ser Trp Gly Asn Val Asp Asn Val Phe Gly

945 950 955 960

Gly Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly

965 970 975

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

980 985 990

Gly Gly Ser Leu Arg Leu Ser Cys Thr Ala Ser Gly Phe Thr Ile Ser

995 1000 1005

Ser Tyr His Met Gln Trp Val Arg Gln Ala Pro Gly Lys Gly Leu

1010 1015 1020

Glu Tyr Ile Gly Thr Ile Ser Ser Gly Gly Asn Val Tyr Tyr Ala

1025 1030 1035

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

1040 1045 1050

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

1055 1060 1065

Ala Val Tyr Tyr Cys Ala Arg Asp Ser Gly Tyr Ser Asp Pro Met

1070 1075 1080

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly

1085 1090 1095

Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly

1100 1105 1110

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

1115 1120 1125

Val Gly Asp Arg Val Thr Ile Thr Cys Gln Ala Ser Gln Asn Ile

1130 1135 1140

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

1145 1150 1155

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

1160 1165 1170

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

1175 1180 1185

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

1190 1195 1200

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

1205 1210 1215

Gly Thr Lys Val Glu Ile Lys

1220 1225

<210> 88

<211> 3678

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 88

cagatcgtgc tgagccagag ccccgccatc ctgagcgcca gccccggcga gaaggtgacc 60

atgacctgcc gggccagcag cagcgtgagc tacatccact ggttccagca gaagcccggc 120

agcagcccca agccctggat ctacgccacc agcaacctgg ccagcggcgt gcccgtgcgg 180

ttcagcggca gcggcagcgg caccagctac agcctgacca tcagccgggt ggaggccgag 240

gacgccgcca cctactactg ccagcagtgg accagcaacc cccccacctt cggcggcggc 300

accaagctga ccgtgctggg tggtggtggc tctggaggag gcgggagcgg gggtggtggc 360

tcaggtggtg gaggttccca ggtgcagctg cagcagcccg gcgccgagct ggtgaagccc 420

ggcgccagcg tgaagatgag ctgcaaggcc agcggctaca ccttcaccag ctacaacatg 480

cactgggtga agcagacccc cggccggggc ctggagtgga tcggcgccat ctaccccggc 540

aacggcgaca ccagctacaa ccagaagttc aagggcaagg ccaccctgac cgccgacaag 600

agcagcagca ccgcctacat gcagctgagc agcctgacca gcgaggacag cgccgtgtac 660

tactgcgccc ggagcaccta ctacggcggc gactggtact tcaacgtgtg gggcgccggc 720

accaccgtga ccgtctcgag tggcggtgga gggtccggcg gtggtggatc agaggtgcag 780

ctggtggagt ctgggggagg cttggtccag cctggggggt ccctgagact ctcctgtgca 840

gcctctggat tcaccatcag taccaatgca atgagctggg tccgccaggc tccagggaag 900

gggctggagt ggatcggagt cattactggt cgtgatatca catactacgc gagctgggcg 960

aaaggcagat tcaccatctc cagagacaat tccaagaaca cgctgtatct tcaaatgaac 1020

agcctgagag ccgaggacac ggctgtgtat tactgtgcga gagacggtgg ttcttctgct 1080

attactagta acaacatttg gggccaggga accctggtca ccgtgtcctc agctagcacc 1140

aagggcccat cggtcttccc cctggcaccc tcctccaaga gcacctctgg gggcacagcg 1200

gccctgggct gcctggtcaa ggactacttc cccgaaccgg tgacggtgtc gtggaactca 1260

ggcgccctga ccagcggcgt gcacaccttc ccggctgtcc tacagtcctc aggactctac 1320

tccctcagca gcgtggtgac cgtgccctcc agcagcttgg gcacccagac ctacatctgc 1380

aacgtgaatc acaagcccag caacaccaag gtggacaaga gagttgagcc caaatcttgt 1440

gacaaaactc acacatgccc accgtgccca gcacctgaag ccgcgggggc accgtcagtc 1500

ttcctcttcc ccccaaaacc caaggacacc ctcatgatct cccggacccc tgaggtcaca 1560

tgcgtggtgg tggacgtgag ccacgaagac cctgaggtca agttcaactg gtacgtggac 1620

ggcgtggagg tgcataatgc caagacaaag ccgcgggagg agcagtacaa cagcacgtac 1680

cgtgtggtca gcgtcctcac cgtcctgcac caggactggc tgaatggcaa ggagtacaag 1740

tgcgcggtct ccaacaaagc cctcccagcc cccatcgaga aaaccatctc caaagccaaa 1800

gggcagcccc gagaaccaca ggtgtacacc ctgcccccat cccgggatga gctgaccaag 1860

aaccaggtca gcctgacctg cctggtcaaa ggcttctatc ccagcgacat cgccgtggag 1920

tggggagagca atgggcagcc ggagaacaac tacaagacca cgcctcccgt gctggactcc 1980

gacggctcct tcttcctcta tagcaagctc accgtggaca agagcaggtg gcagcagggg 2040

aacgtcttct catgctccgt gatgcatgag gctctgcaca accactacac gcagaagagc 2100

ctctccctgt ctccgggtgg cggtggaggg tccggcggtg gtggatccga ggtgcagctg 2160

ttggagtctg ggggaggctt ggtacagcct ggggggtccc tgagactctc ctgtgcagcc 2220

tctggattct ccttcagtag cgggtacgac atgtgctggg tccgccaggc tccagggaag 2280

gggctggagt ggatcgcatg cattgctgct ggtagtgctg gtatcactta cgacgcgaac 2340

tgggcgaaag gccggttcac catctccaga gacaattcca agaacacgct gtatctgcaa 2400

atgaacagcc tgagagccga ggacacggcc gtatattact gtgcgagatc ggcgttttcg 2460

ttcgactacg ccatggacct ctggggccag ggaaccctgg tcaccgtgtc gagcggtgga 2520

ggcggatctg gcggaggtgg ttccggcggt ggcggctccg gtggaggcgg ctctgacatc 2580

cagatgaccc agtctccttc caccctgtct gcatctgtag gagacagagt caccatcact 2640

tgccaggcca gtcagagcat tagttcccac ttaaactggt atcagcagaa accagggaaa 2700

gcccctaagc tcctgatcta taaggcatcc actctggcat ctggggtccc atcaaggttc 2760

agcggcagtg gatctgggac agaatttact ctcaccatca gcagcctgca gcctgatgat 2820

tttgcaactt attactgcca acagggttat agttggggta atgttgataa tgttttcggc 2880

ggagggacca aggtggagat caaaggcggt ggagggtccg gcggtggtgg ctccggacgg 2940

tcgctggtgg agtctggggg aggcttggtc cagcctgggg ggtccctgag actctcctgt 3000

actgcctctg gattcaccat cagtagctac cacatgcagt gggtccgcca ggctccaggg 3060

aaggggctgg agtacatcgg aaccattagt agtggtggta atgtatacta cgcaagctcc 3120

gctagaggca gattcaccat ctccagaccc tcgtccaaga acacggtgga tcttcaaatg 3180

aacagcctga gagccgagga cacggctgtg tattactgtg cgagagactc tggttatagt 3240

gatcctatgt ggggccaggg aaccctggtc accgtctctt caggcggtgg cggtagtggg 3300

ggaggcggtt ctggcggcgg agggtccggc ggtggaggat cagacgttgt gatgacccag 3360

tctccatctt ccgtgtctgc atctgtagga gacagagtca ccatcacctg tcaggccagt 3420

cagaacatta ggacttactt atcctggtat cagcagaaac cagggaaagc ccctaagctc 3480

ctgatctatg ctgcagccaa tctggcatct ggggtcccat caaggttcag cggcagtgga 3540

tctgggacag atttcactct caccatcagc gacctggagc ctggcgatgc tgcaacttac 3600

tattgtcagt ctacctatct tggtactgat tatgttggcg gtgctttcgg cggagggacc 3660

aaggtggaga tcaaatga 3678

<210> 89

<211> 475

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 89

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Val Thr Val Leu Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Leu

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser

245 250 255

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

260 265 270

Asp Arg Val Thr Ile Asn Cys Gln Ala Ser Glu Ser Ile Ser Ser Trp

275 280 285

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

290 295 300

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

305 310 315 320

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

325 330 335

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gly Tyr Phe Tyr Phe Ile Ser

340 345 350

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

355 360 365

Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu

370 375 380

Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe

385 390 395 400

Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln

405 410 415

Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser

420 425 430

Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu

435 440 445

Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser

450 455 460

Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys

465 470 475

<210> 90

<211> 1425

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 90

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggcagggg 300

acaaaagtga cggtactggg tggaggcggt tcaggcggag gtggttccgg cggtggcggc 360

tccggtggag gcggctctca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttaggctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaaggtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg cgcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tctcgagcgg cggtggaggg tccggcggtg gtggatcaga cgtcgtgatg 780

acccagtctc cttccaccct gtctgcatct gtaggagaca gagtcaccat caattgccaa 840

gccagtgaga gcattagcag ttggttagcc tggtatcagc agaaaccagg gaaagcccct 900

aagctcctga tctatgaagc atccaaactg gcatctgggg tcccatcaag gttcagcggc 960

agtggatctg ggacagaatt cactctcacc atcagcagcc tgcagcctga tgattttgca 1020

acttattact gccaaggcta tttttatttt attagtcgta cttatgtaaa ttctttcggc 1080

ggagggacca aggtggagat caaacgtacg gtggctgcac catctgtctt catcttcccg 1140

ccatctgatg agcagttgaa atctggaact gcctctgttg tgtgcctgct gaataacttc 1200

tatcccagag aggccaaagt acagtggaag gtggataacg ccctccaatc gggtaactcc 1260

caggagagtg tcacagagca ggacagcaag gacagcacct acagcctcag cagcaccctg 1320

acgctgagca aagcagacta cgagaaacac aaagtctacg cctgcgaagt cacccatcag 1380

ggcctgagct cgcccgtcac aaagagcttc aacaggggag agtgt 1425

<210> 91

<211> 120

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 91

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

1 5 10 15

Thr Leu Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser

20 25 30

Gly Met Gly Val Gly Trp Ile Arg Gln Pro Pro Gly Lys Cys Leu Glu

35 40 45

Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala

50 55 60

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

65 70 75 80

Tyr Leu Gln Met Asn Ser Leu Asp Ala Glu Asp Thr Ala Val Tyr Tyr

85 90 95

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

100 105 110

Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 92

<211> 360

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 92

caggtcacat tgaaggaatc tggccccggc cttgttcagc caggacagac ccttaggctc 60

acctgtgcct tcagtggttt ttctcttagc actagcggta tgggggtcgg ctggattcgg 120

cagcctcccg gcaaatgtct tgagtggttg gctcacattt ggtgggacga cgacaaacgg 180

tataatcctg ccttgaaaag tcggctgacc attagtaagg atacctcaaa aaatcaagtg 240

tacttgcaaa tgaatagcct tgacgccgag gatacggctg tatattattg cgctcggatg 300

gaactctggt cttactactt tgattattgg gggcagggga ctctcgtcac ggtgtcgagt 360

<210> 93

<211> 106

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 93

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Cys Gly Thr Lys Val Glu Ile Lys

100 105

<210> 94

<211> 318

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 94

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggtgtggg 300

acaaaagtgg agatcaag 318

<210> 95

<211> 246

<212> PROTEIN

<213> Artificial sequence

<220>

<223> Synthetic

<400> 95

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

1 5 10 15

Glu Arg Val Thr Ile Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Asn Asp His Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Thr Tyr Tyr Cys Phe Gln Gly Ser Val Tyr Pro Phe Thr

85 90 95

Phe Gly Cys Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly

100 105 110

Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val

115 120 125

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

130 135 140

Arg Leu Thr Cys Ala Phe Ser Gly Phe Ser Leu Ser Thr Ser Gly Met

145 150 155 160

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

165 170 175

Ala His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

Leu Val Thr Val Ser Ser

245

<210> 96

<211> 738

<212> DNA

<213> Artificial sequence

<220>

<223> Synthetic

<400> 96

gaaaatgtat tgacacagag ccccgcctcc ctcagtgcct cacctgggga aagggtaact 60

atcacttgct ctgcatcaag cagcgtctca tacatgcatt ggtatcaaca aaagcctgga 120

caggccccca agctctggat atacgatacg agcaagctgg cttccggcgt acctagccgc 180

ttcagtggtt ccggctcagg caacgatcac acccttacga tttccagtat ggaacccgaa 240

gattttgcaa cttattattg tttccagggg agcgtgtacc cattcacttt cgggtgtggg 300

acaaaagtgg agatcaaggg tggcggaggc agtggtggcg ggggcagcgg aggtggtggt 360

tcaggggggtg gtgggagcca ggtcacattg aaggaatctg gccccggcct tgttcagcca 420

ggacagaccc ttaggctcac ctgtgccttc agtggttttt ctcttagcac tagcggtatg 480

ggggtcggct ggattcggca gcctcccggc aaatgtcttg agtggttggc tcacatttgg 540

tgggacgacg acaaacggta taatcctgcc ttgaaaagtc ggctgaccat tagtaaggat 600

acctcaaaaa atcaagtgta cttgcaaatg aatagccttg acgccgagga tacggctgta 660

tattattgcg ctcggatgga actctggtct tactactttg attattgggg gcaggggact 720

ctcgtcacgg tgtcgagt 738

<---

Claims (38)

1. An scFv peptide having binding specificity for human CD19, comprising the amino acid sequence of the heavy chain variable region of SEQ ID NO: 7 and the amino acid sequence of the light chain variable region of SEQ ID NO: 19. 2. The scFv peptide according to claim 1, having a KD of no more than 10 nM when binding to human CD19. 3. An antibody having binding specificity to human CD19, wherein said antibody comprises the peptide of claim 1. 4. The antibody according to claim 3, wherein said antibody is a multispecific antibody. 5. The antibody of claim 3, comprising an scFv, wherein said scFv comprises the peptide of claim 1. 6. The antibody of claim 3, comprising a Fab, wherein said Fab comprises a peptide of claim 1. 7. A multispecific antibody-like protein having binding specificity for human CD19, αEGFR, αPD-L1, α4-1BB, αHER3 and αCD3a, comprising the peptide of claim 1, wherein the multispecific antibody-like protein has an N-terminus and a C-terminus comprising, in order from N-terminus to C-terminus: the first binding structural domain at the N-terminus, the second binding structural domain containing part of the light chain, Fc region, the third binding structural domain and the fourth binding structural domain (D4) at the C-terminus, wherein the light chain portion comprises a fifth binding structural domain covalently linked to the C-terminus, a sixth binding structural domain covalently linked to the N-terminus, or both, and wherein each of the first binding structural domain, the second binding structural domain, the third binding structural domain, the fourth binding structural domain, the fifth binding structural domain and the sixth binding structural domain has specificity for human CD19, αEGFR, αPD-L1, α4-1BB, αHER3 and αCD3a. 8. A multispecific antibody-like protein according to claim 7, wherein the first binding structural domain comprises the peptide according to claim 1. 9. A multispecific antibody-like protein according to claim 7, wherein the first binding structural domain comprises a peptide comprising the amino acid sequence of the variable region of the heavy chain of SEQ ID NO: 7 and the amino acid sequence of the variable region of the light chain of SEQ ID NO: 19. 10. The multispecific antibody-like protein of claim 7, wherein the second binding structural domain comprises the peptide of claim 1. 11. A multispecific antibody-like protein according to claim 7, wherein the sixth binding structural domain comprises the peptide according to claim 1. 12. A multispecific monoclonal antibody having binding specificity for human CD19, comprising the multispecific antibody-like protein of claim 8. 13. A multispecific monoclonal antibody according to claim 12, having a binding affinity for human CD19 with a Kd of no more than 10 nM. 14. A multispecific monoclonal antibody according to claim 12, wherein said antibody is a humanized antibody. 15. The multispecific monoclonal antibody of claim 12, wherein the antibody is IgG. 16. An isolated nucleic acid encoding a multispecific monoclonal antibody according to claim 12. 17. An expression vector containing the isolated nucleic acid of claim 16. 18. A CHO host cell producing a multispecific monoclonal antibody containing the nucleic acid of claim 16. 19. A method for producing an antibody comprising culturing a host cell according to claim 18 so that the antibody is produced. 20. An antibody-drug conjugate having binding specificity for human CD19, comprising a multispecific monoclonal antibody according to claim 12 and a drug unit that is a cytotoxic agent, an immunoregulatory agent, an imaging agent, or a combination thereof, and wherein the drug unit is linked to the multispecific monoclonal antibody via a linker and wherein the linker comprises a covalent bond selected from an ester bond, an ether bond, an amino bond, an amide bond, a disulfide bond, an imide bond, a sulfone bond, a phosphate bond, a phosphorus ester bond, a peptide bond, a hydrazone bond, or a combination thereof. 21. The antibody-drug conjugate of claim 20, wherein the cytotoxic agent is selected from a tumor growth inhibitory agent or a chemotherapeutic agent from the class of tubulin binders, DNA intercalators, DNA alkylators, enzyme inhibitors, immunomodulators, antimetabolites, radioactive isotopes, or combinations thereof. 22. The antibody-drug conjugate of claim 20, wherein the cytotoxic agent is selected from calicheamicin, camptothecin, ozagomicin, monomethyl auristatin E, trastuzumab, derivatives thereof, or combinations thereof. 23. The antibody-drug conjugate of claim 20, wherein the immunoregulatory reagents activate or suppress immune cells, T cells, NK cells, B cells, macrophages, or dendritic cells. 24. The antibody-drug conjugate of claim 20, wherein said imaging agent may be a radionuclide, a fluorophore, a quantum dot, or a combination thereof. 25. A pharmaceutical composition for treating a malignant tumor expressing CD19, comprising a multispecific monoclonal antibody according to claim 12 and a pharmaceutically acceptable carrier. 26. The pharmaceutical composition of claim 25, further comprising a chemotherapeutic agent, a tumor growth inhibitory agent, a cytotoxic agent from the calicheamicin class, an antimitotic agent, a toxin, a radioactive isotope, a therapeutic agent, or a combination thereof. 27. A pharmaceutical composition for treating a malignant tumor expressing CD19, comprising an antibody-drug conjugate according to claim 20 and a pharmaceutically acceptable carrier. 28. Use of a multispecific monoclonal antibody according to claim 12 for the manufacture of a medicament for the treatment of a subject suffering from a malignant tumor expressing CD19. 29. The use according to claim 28, wherein said medicinal product is administered together with an effective amount of a therapeutic agent, wherein said therapeutic agent comprises an antibody, a chemotherapeutic agent, an enzyme, or a combination thereof. 30. The use according to paragraph 29, where the said subject is a human being.