EA046596B1 - SOLUBILIZED APYRASES, METHODS AND APPLICATION - Google Patents

Description

Field of technology

The present invention relates to the development and therapeutic use of solubilized polypeptide apyrases, pharmaceutical compositions and methods useful for the prevention and treatment of tissue damage.

BACKGROUND OF THE INVENTION

Apyrase (ATP diphosphatase, adenosine diphosphatase, ADPase or ATP diphosphohydrolase) is a group of cytoplasmic membrane-bound enzymes active on both nucleotide di- and triphosphates (NDP and NTP) and hydrolyzing NTP to produce nucleotide monophosphates (NMP) in two separate sequential steps that release phosphate, with NDPs acting as intermediates. Most ecto-ATPases that occur on the cell surface and hydrolyze extracellular nucleotides belong to this family of enzymes. They differ from ATPases, which specifically hydrolyze ATP, in that they hydrolyze both ATP and ADP.

The first known human apyrase, ectonucleoside triphosphate diphosphohydrolase-1 (gene: ENTPD1, protein: NTPDa3a 1), also known as cluster of differentiation 39 (CD39, UniProt P49961, or SEQ ID NO: 1) is a cell surface-localized enzyme with a catalytic center facing the extracellular space.

In the known human CD39 family, its member CD39L3 is known as ectoapyrase (ectoATPDase) and is intermediate in biochemical activity between CD39 and CD39L1 (ecto-ATPase). In particular, human CD39L3 has been solubilized and purified for therapeutic purposes, for example, as disclosed in US7247300B1 (incorporated herein by reference) or incorporated herein under SEQ ID NO: 3.

Brief description of the invention

The present invention is based, among other things, on the unexpected discovery that certain modifications of solubilized human apyrase, such as human CD39, result in a remarkably active protein that is at the same time safe and easy to manufacture.

According to a first aspect of the present invention, there is provided a solubilized human apyrase containing at least two modifications selected from the list consisting of an N-terminal deletion, a C-terminal deletion, and a core region modification.

In one embodiment, the solubilized human apyrase contains an N-terminal deletion, a C-terminal deletion, and a deletion modification.

In one embodiment, modification of the central region includes deletion of one or more amino acids. In another embodiment, the modification of the central region includes a point mutation of one or more amino acids, such as a substitution mutation. In yet another embodiment, the modification of the central region is a combination of a deletion of one or more amino acids and a point mutation, such as a substitution mutation, of one or more amino acids.

The N-terminal deletion may be a deletion of 30 to 50 amino acids at the N-terminus of the wild-type CD39 sequence of SEQ ID NO: 1, such as deletion 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 , 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 amino acids. In a preferred embodiment, the N-terminal deletion is a deletion of 34, 37, 38 or 45 amino acids.

The C-terminal deletion may be a deletion of 20 to 40 amino acids at the C-terminus of the wild-type CD39 sequence of SEQ ID NO: 1, such as deletion 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 , 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 or 40 amino acids. In a preferred embodiment, the C-terminal deletion is a deletion of 22, 29 or 37 amino acids.

The deletion in the central region may be a deletion of 10 to 15 contiguous amino acids of the wild-type CD39 sequence of SEQ ID NO: 1, such as a deletion of 10, 11, 12, 13, 14, or 15 amino acids. In a preferred embodiment, the deletion in the central region is a deletion of 12 amino acids, such as amino acids 193 to 204, relative to the wild-type CD39 sequence of SEQ ID NO: 1.

In one embodiment, the solubilized human apyrase contains one, two, three, four, or five point mutations relative to the wild-type CD39 sequence of SEQ ID NO: 1 selected from the group consisting of K71E, N73Q, V95A, G102D, Y104S, T106S , R113M, L149M, V151A, E173D, T229A, L254M, K258R, W263R, E276D, N292Q, R304G, I319T, N327Q, A362N, F365S, N371Q, K405N, Y412F, L424Q, H436D, 437N, F439S, G441D, N457Q, P463S , and S469R.

In one embodiment, the solubilized human apyrase contains a sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 32, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 70, SEQ ID NO: 76, and SEQ ID NO: 78.

In one embodiment, the solubilized human apyrase contains a sequence selected from the group consisting of SEQ ID NO: 131, SEQ ID NO: 133, SEQ ID NO: 135, SEQ ID NO: 137, SEQ ID NO: 139, and SEQ ID NO: 141.

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In one specific embodiment, the solubilized human apyrase contains a sequence selected from the group consisting of SEQ ID NO: 213, SEQ ID NO: 227, SEQ ID NO: 219, SEQ ID NO: 227, SEQ ID NO: 217, SEQ ID NO : 209, SEQ ID NO: 221, SEQ ID NO: 72, SEQ ID NO: 215, SEQ ID NO: 223, SEQ ID NO: 211, SEQ ID NO: 58 and SEQ ID NO: 229.

In one specific embodiment, the solubilized human apyrase consists of a sequence selected from the group consisting of SEQ ID NO: 213, SEQ ID NO: 227, SEQ ID NO: 219, SEQ ID NO: 227, SEQ ID NO: 217, SEQ ID NO: 209, SEQ ID NO: 221, SEQ ID NO: 72, SEQ ID NO: 215, SEQ ID NO: 223, SEQ ID NO: 211, SEQ ID NO: 58 and SEQ ID NO: 229.

In a preferred embodiment, the solubilized human apyrase contains a sequence selected from the group consisting of SEQ ID NO: 58, SEQ ID NO: 72 and SEQ ID NO: 229.

In one embodiment, the solubilized human apyrase contains SEQ ID NO: 58. In one embodiment, the solubilized human apyrase contains SEQ ID NO: 72. In one embodiment, the solubilized human apyrase contains SEQ ID NO: 229.

In a preferred embodiment, the solubilized human apyrase consists of a sequence selected from the group consisting of SEQ ID NO: 58, SEQ ID NO: 72 and SEQ ID NO: 229.

In one embodiment, the solubilized human apyrase consists of SEQ ID NO: 58. In one embodiment, the solubilized human apyrase consists of SEQ ID NO: 72. In one embodiment, the solubilized human apyrase consists of SEQ ID NO: 229.

In accordance with a second aspect of the present invention, the present invention relates to a pharmaceutical composition comprising a therapeutically effective dose of apyrase according to the first aspect of the present invention and one or more pharmaceutically acceptable carriers provided.

In one embodiment, the pharmaceutical composition further contains one or more additional active ingredients.

According to a third aspect of the present invention, an isolated apyrase according to the first aspect is provided for use as a drug.

In accordance with a fourth aspect of the present invention, an isolated apyrase according to the first aspect is provided for use in the treatment of tissue damage.

The tissue damage may be acute brain injury (stroke); acute multiple organ failure; delayed graft function after kidney or other solid organ transplantation; burn; radiation injury; acute injury due to trauma and/or hypoxia, such as acute respiratory distress syndrome (ARDS) or lung injury; acute kidney injury, such as acute kidney injury due to chest surgery (eg, aortic valve replacement, coronary artery bypass grafting), or sepsis, or rhabdomyolysis, or the toxic effects of antibiotics or other drugs; acute myocardial injury.

In another embodiment, the fourth aspect of the present invention provides an isolated apyrase according to the first aspect of the present invention for use in the treatment of acute kidney injury associated with cardiac surgery.

In another embodiment, the fourth aspect of the present invention provides an isolated apyrase according to the first aspect of the present invention for use in the treatment of delayed graft function (DGF), acute respiratory distress syndrome (ARDS), acute myocardial infarction (AMI), traumatic brain injury (TB1) )/acute ischemic stroke (AIS), ischemia-reperfusion injury (IRI), or combinations thereof, often referred to as multiple organ failure (MOF) forms.

In one embodiment, the solubilized human apyrase used for the treatment of acute kidney injury associated with cardiac surgery contains the amino acid sequence of SEQ ID NO: 58.

In one embodiment, the solubilized human apyrase used for the treatment of acute kidney injury associated with cardiac surgery contains the amino acid sequence of SEQ ID NO: 72. In one embodiment, the solubilized human apyrase used for the treatment of acute kidney injury associated with cardiac surgery heart surgery, contains the amino acid sequence of SEQ ID NO: 229.

In a further preferred embodiment, the present invention relates to the use of an isolated apyrase according to the first aspect of the present invention for the treatment of acute kidney injury associated with sepsis.

In one embodiment of the fourth aspect, the solubilized human apyrase

- 2 046596 for use in the treatment of acute kidney injury associated with sepsis, contains the amino acid sequence of SEQ ID NO: 58.

In one embodiment of the fourth aspect, the solubilized human apyrase for use in the treatment of acute kidney injury associated with sepsis comprises the amino acid sequence of SEQ ID NO: 72.

In one embodiment of the fourth aspect, the solubilized human apyrase for use in the treatment of acute kidney injury associated with sepsis comprises the amino acid sequence of SEQ ID NO: 229.

In accordance with a fifth aspect of the present invention, there is provided a method of treating tissue damage in a human subject, comprising administering to said subject a therapeutically effective dose of solubilized human apyrase according to the first aspect. One embodiment of the fifth aspect of the present invention relates to a method of treating acute kidney injury associated with cardiac surgery, comprising administering to a subject in need of such treatment a therapeutically effective dose of an isolated apyrase according to the first aspect of the present invention.

Another embodiment of the fifth aspect of the present invention relates to a method of treating delayed graft function (DGF), acute respiratory distress syndrome (ARDS), acute myocardial infarction (AMI), traumatic brain injury (TBI)/acute ischemic stroke (AIS), ischemic -reperfusion injury (IRI) or combinations thereof, often referred to as forms of multiple organ failure (MOF), comprising administering to a subject in need of such treatment a therapeutically effective dose of an isolated apyrase according to the first aspect of the present invention.

In one embodiment of the fifth aspect, the solubilized human apyrase used in a method of treating acute kidney injury associated with cardiac surgery comprises the amino acid sequence of SEQ ID NO: 58, SEQ ID NO: 72, or SEQ ID NO: 229.

One embodiment of the fifth aspect of the present invention relates to a method of treating acute kidney injury associated with sepsis, comprising administering to a subject in need of such treatment a therapeutically effective dose of an isolated apyrase according to the first aspect of the present invention.

In one embodiment of the fifth aspect, the solubilized human apyrase used in a method of treating acute kidney injury associated with sepsis comprises the amino acid sequence of SEQ ID NO: 58, SEQ ID NO: 72, or SEQ ID NO: 229. The tissue damage may be acute brain damage (stroke); acute multiple organ failure; delayed graft function after kidney or other solid organ transplantation; burn; radiation injury; acute injury due to trauma and/or hypoxia, such as acute respiratory distress syndrome (ARDS) or lung injury; acute kidney injury, such as acute kidney injury due to chest surgery (eg, aortic valve replacement, coronary artery bypass grafting), or sepsis, or rhabdomyolysis, or the toxic effects of antibiotics or other drugs; acute myocardial injury.

According to a sixth aspect of the present invention, there is provided an isolated nucleic acid molecule encoding any apyrase according to the first aspect.

According to a seventh aspect of the present invention, there is provided a cloning or expression vector containing one or more nucleic acid sequences according to the sixth aspect, wherein the vector is suitable for recombinantly producing isolated apyrase according to the first aspect.

In accordance with the eighth aspect of the present invention, there is provided a host cell containing one or more cloning or expression vectors according to the seventh aspect.

According to a ninth aspect of the present invention, there is provided a method for producing apyrase according to the first aspect, comprising culturing a host cell according to the eighth aspect, purifying and recovering said apyrase.

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Brief description of graphic materials

In fig. 1 shows the sequence alignment;

in fig. 2A shows the expression level of human CD39 in a supernatant containing it determined by Western blotting using an anti-APP antibody in accordance with an embodiment;

in fig. 2B shows the expression level of human CD39 cysteine bridge deletion variants in a supernatant containing them, determined by Western blotting using an anti-APP antibody in accordance with an embodiment;

in fig. 3 is a graph showing the results of the ATPase enzyme-linked assay for CD39 variants;

in fig. 4 is a graph showing solid-phase ATP cleavage on HEK293 cells transformed with human CD39 variants in accordance with an embodiment;

in fig. 5 is a vector diagram according to an embodiment;

in fig. 6 shows a model of enzymatic activity based on a stationary approximation;

in fig. 7 provides an overview of kinetic data and model fit for a protein in accordance with an embodiment;

in fig. 8 provides an overview of kinetic data and model fit for a protein in accordance with an embodiment;

in fig. 9 provides an overview of kinetic data and model fit for a protein in accordance with an embodiment;

in fig. 10 shows a schematic representation of the experimental conditions;

in fig. 11 is a graph showing AMP levels for proteins in accordance with embodiments; and in fig. 12 are graphs showing in vivo results for proteins in accordance with embodiments.

Detailed Description of the Invention

The present invention is based, among other things, on the unexpected discovery that certain modifications of solubilized CD39 result in a surprisingly active protein that is safe and easy to manufacture.

As will be shown in the specific examples below, a preferred embodiment is a solubilized human apyrase containing at least two modifications selected from the list consisting of an N-terminal deletion, a C-terminal deletion, and a central region deletion, such as a solubilized human apyrase, comprising a sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 32, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 70, SEQ ID NO: 76 , and SEQ ID NO: 78.

The present inventors have tried several different sequence modification strategies in order to obtain solubilized human apyrase with both retained activity and ability to be expressed, while at the same time not introducing too many modifications due to the risk of increasing immunogenicity and thus increased security risk. Surprisingly, one of the sequence modifications that was found to simultaneously increase both the potency and expressibility of human apyrase, while not adding too much risk of immunogenicity, was a deletion in the central region—a so-called delta modification. MIL (ΔΜΙΡ).

To enhance the expression of solubilized human apyrase in accordance with embodiments of the present invention, N-terminal expression tags were tested. Various N-terminal expression tags are known in the art, but surprisingly, not all tags were functional. The present inventors discovered that only some of the tags were functioning, which could not be predicted.

These N-terminal tags were SEQ ID NO: 131, SEQ ID NO: 133, SEQ ID NO: 135, SEQ ID NO: 137, SEQ ID NO: 139, or SEQ ID NO: 141. As shown herein, particularly preferred tags are SEQ ID NO: 133, SEQ ID NO: 135, or SEQ ID NO: 137.

Specific details are set forth in Examples 9-13 below. However, to illustrate the unpredictable nature of these examples, Table. 1 provides a comparative summary overview.

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Table 1

Summary of Preferred Embodiments

Design Modifications Activity compared to parent EP28 Titer (g/l) N terminal number Number of points In vitro In vivo amino acids from SEQIDNO: 131 mutations EP1xEP17 6 2 1.5x 0.6 EP17xEP19 6 2 1.5x 0.26 EP1xEP17xEP19 6 3 1.5x 0.46 EP17xEP19 3 2 1.5x 0.40 EP1xEP17xEP19 3 3 1.5x 0.58 EP1 3 1 1x 0.29 EP1xEP14 3 2 4x 0.50 EP28 16 0 1x lx 0.08 ΕΡ1χΕΡ17_Κ405Ν 15 3 1.5x lx 1.4 EP1xEP14 6 2 4x 0.3 EP1xEP17 3 2 1.5x 0.68 EP28 3 0 1x 0.10 EP14 3 1 4x 4x 0.27

1. Definitions.

To facilitate the practice of the present invention by one skilled in the art, the following terms are used throughout this specification.

The terms CD39 and hCD39 are used synonymously throughout the present invention and, unless otherwise stated, refer to human cluster of differentiation 39 (CD39) according to UniProt P49961 or SEQ ID NO: 1.

The term apyrase refers to human apyrase unless otherwise noted. The term solubilized apyrase as used herein means that apyrase, which, as a wild-type protein, exists in a form associated with the cell membrane, has been modified such that it is no longer associated with the cell membrane, but exists in a soluble state, i.e., no longer anchored to the cell membrane.

The abbreviation MIL refers to membrane interacting loop, which is the central portion of the wild-type (human) CD39 protein that interacts with the cell membrane, in addition to the N-terminal and C-terminal portions that are physically anchored to the cell membrane. The term delta-MIL or AMIL refers to a deletion of the MIL sequence in wild-type (human) CD39.

The term approximately in relation to the numerical value of x means, for example, +/- 10%. When used before a numeric range or list of numbers, the term approximately applies to each number in the series, for example, the phrase about 1-5 should be interpreted as from about 1 to about 5, or, for example, the phrase about 1, 2, 3, 4 should be interpreted like about 1, about 2, about 3, about 4, etc.

The word essentially does not exclude completely, for example, a composition that is essentially free of Y may be completely free of Y. If necessary, the word essentially can be omitted from the definition of the present invention.

The term containing covers including as well as consisting, for example, a composition containing X may consist solely of X or may include something additional, for example X+Y.

The term identity, with respect to a native polypeptide and its functional derivative, is defined herein as the percentage of amino acid residues in a candidate sequence that are identical to those of the corresponding native polypeptide after sequence alignment and, if necessary, introduction of gaps to achieve the maximum percentage of identity, and without regard to any conservative substitutions as part of sequence identity. Neither N- or C-terminal extensions nor insertions should be considered as reducing

- 5 046596 identity. Methods and computer programs for alignment are well known. Percent identity can be determined using standard alignment algorithms, such as the Basic Local Alignment Search Tool (BLAST) described by Altshul et al. ((1990) J. Mol. Biol., 215: 403-410); algorithm by Needleman et al. ((1970) J. Mol. Biol., 48: 444-453) or the algorithm of Meyers et al. ((1988) Comput. Appl. Biosci., 4: 11-17). The set of parameters can be a Blosum 62 weight matrix with a gap penalty of 12, a gap extension penalty of 4, and a frameshift gap penalty of 5. The percentage of identity between two amino acid or nucleotide sequences can also be determined using the algorithm of E. Meyers and W. Miller ((1989) CABIOS, 4:11-17), which was included in the ALIGN program (version 2.0), using the PAM120 residue substitution weight table, the gap-extension penalty of 12, and the gap-introduction penalty of 4.

The term amino acid(s) refers, for example, to all naturally occurring Lα-amino acids and includes D-amino acids. The phrase amino acid sequence variant refers to molecules with some differences in their amino acid sequences compared to the sequences of the present invention. Variants of the amino acid sequence of the protein according to the present invention, for example, with the specified sequence, still have apyrase activity. Amino acid sequence variants include substitution variants (variants in which at least one amino acid residue has been deleted and another amino acid has been inserted in its place at the same position in the polypeptide of the present invention), insertion variants (variants with one or more amino acids inserted in close proximity to an amino acid at a specific position in the polypeptide of the present invention) and deletion variants (variants in which one or more amino acids are deleted in the polypeptide of the present invention).

The term treating or treating is defined herein as the use or administration to a subject of an apyrase according to the present invention, or the use or administration to a subject or an isolated tissue or cell line obtained from a subject, of a pharmaceutical composition containing said apyrase, where the subject has a tissue injury, symptom, associated with tissue damage, where the goal is to attenuate, reduce the intensity or improve the course of tissue damage or any associated symptoms of tissue damage, among other things, by reducing the levels of extracellular ATP.

The term treatment is also intended to mean the use or administration to a subject of a pharmaceutical composition containing an apyrase, or the use or administration to an isolated tissue or cell line obtained from a subject of a pharmaceutical composition containing an apyrase of the present invention, where the subject has a tissue injury or symptom associated with tissue damage, where the goal is to attenuate, reduce the intensity of, or improve the course of tissue damage or any associated symptoms of tissue damage.

The term prevent or prevention refers to prophylactic or preventive treatment; it refers to delaying the onset of manifestation or preventing the onset of manifestation of a disease, disorders and/or symptoms associated with it.

As used herein, a subject requires treatment if, as a result of such treatment, such subject would benefit from a biological, medical, or quality of life perspective.

The term pharmaceutically acceptable means a non-toxic material that does not interfere with the effectiveness of the biological activity of the active ingredient(s).

As used herein, the term administer or administration of a subject compound means providing a compound of the present invention and its prodrugs to a subject in need of treatment. Administration in combination with one or more additional therapeutic agents includes simultaneous (parallel) and sequential administration in any order and by any route of administration.

As used herein, the term therapeutically effective dose refers to a dose (amount) of apyrase that is effective when administered in single or multiple doses to a patient (such as a human) to treat, prevent, prevent the onset of, cure, delay, reduce the severity, reduce the intensity of at least one symptom disorder or recurrent disorder or prolongation of patient survival beyond what would be expected in the absence of such treatment. When used in relation to an individual active ingredient (eg, apyrase) that is administered separately, the term refers only to that ingredient. When used in relation to a combination, the term refers to the combined doses or amounts of active ingredients that produce a therapeutic effect, whether administered in combination, sequentially or simultaneously.

The phrase dosing regimen means a regimen used to treat a disease, such as a dosing protocol used during the treatment of tissue damage.

The phrase means of administration is used to refer to any available instrument for the systemic administration of a drug to a patient, including but not limited to

- 6 046596 filled syringe, vial and syringe, pen syringe, auto-injector, intravenous (i.v.) drip and bag, pump, patch pump, etc. With the help of such products, the patient can administer the drug himself (i.e. self-administer the medicine), or the medicine can be administered by a doctor.

2. Example 1: Non-membrane bound CD39.

Wild-type human CD39 apyrase (hCD39, UniProt P49961 or SEQ ID NO: 1) is naturally anchored in the cell membrane by a transmembrane domain at the N terminus (putatively represented by aa 17-37), a putative central loop that interacts with membrane (MIL, presumably represented by aa 193-204), and the C-terminal transmembrane domain (presumably represented by aa 479-499). To enable expression of a soluble variant of CD39 using a mammalian host cell, several elements of the CD39 sequence were modified to produce a non-membrane bound, or solubilized, protein. The native leader sequence and N-terminal transmembrane region were replaced with a secretory leader sequence and purification tag (SEQ ID NO: 133). The boundaries of the CD39 extracellular domain were modified to optimize expression, purification and activity parameters (amino acids Nos. 38-476 of SEQ ID NO: 1, amino acids Nos. 39-469 of SEQ ID NO: 1, amino acids 46-461 of SEQ ID NO: 1 and amino acids 46-476 from SEQ ID NO: 1 respectively). The effect of cysteine residues and disulfide bridges on aggregation propensity and enzymatic activity was systematically assessed by replacing the cysteine residues with alanine or by shortening the loop formed by the disulfide bridge (SEQ ID NOs: 107, 109, 111, 113 and 115). The hydrophobic amino acid fragment was described in the work on the structure of rat CD39 (Zebisch et al., J. Mol. Biol. (2012), 415, 288-306, wild-type rat CD39, Uniprot P97687, presented under SEQ ID NO: 2 ), and there is reason to believe that this loop can interact with the cell membrane (MIL). We applied these findings to the human CD39 sequence by sequence alignment and obtained CD39 loop deletion variants (CD39ΔMIL or EP28, provided at SEQ ID NO: 4). The effect of MIL deletion (or delta/Δ) on functional CD39 expression levels and thermal stability was assessed.

As can be seen in FIG. 1, which shows a sequence alignment of SEQ ID NO: 1 and SEQ ID NO: 4, N-terminal amino acids 1-27, C-terminal amino acids 477-510 and amino acids 193-204 of the central membrane interacting loop (MIL) were subjected to deletion in wtCD39 (SEQ ID NO: 1) to form CD39ΔMIL (SEQ ID NO: 4).

The effect of various sequence modifications on thermal stability was studied. In addition, the effect of various sequence modifications on expression yield and monomer content on CHO cells was studied.

(1) Methods.

(a) Preparation of expression plasmids.

DNA sequences encoding hCD39 with various boundary variants and membrane interacting loop (MIL) deletion were ordered from GeneArt (Life Technologies Inc., Regensburg, Germany) with codon optimization for Homo sapiens. Sequences encoding hCD39 variants were subcloned using standard molecular biology techniques from vectors obtained at GeneArt or variants obtained in-house into an expression vector suitable for secretion in mammalian cells. In the modified oligonucleotides, mutations such as replacement of cysteine with alanine, present in variants with deletion of the cysteine bridge, were targeted, and after a subsequent stage of assembly PCR, the resulting fragments were subcloned into the same expression vector mentioned earlier. Expression vector elements include a promoter (cytomegalovirus (CMV) enhancer-promoter tandem), a signal sequence to facilitate secretion, a polyadenylation signal, and a transcription terminator (bovine growth hormone (BGH) gene), an element enabling episomal replication and replication in prokaryotes ( for example, the origin of replication of SV40 and ColE1 or others known in the art), and elements to enable selection (ampicillin resistance gene and zeocin resistance marker). A list of truncated, solubilized variants of human CD39 is presented in Table. 2, where the numbering of amino acid modifications is carried out in relation to SEQ ID NO: 1.

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Truncated, with Reference name CD39(aa39-469) CD39(aa46-476) Table 2 solubilized amino acid var sequences SEQ GO NO: 99 SEQIDNO: 101 Human CD39 ants Modification(s) N- and C-terminal truncations N- and C-terminal truncations CD39(aa46-461) SEQ GO NO: 103 N- and C-terminal truncations CD39(aa46- 461)_dMIL(193-204) SEQ GO NO: 105 N- and C-terminal truncations and deletion in the central region CD39(aa46-461)_deltacysl SEQ GO NO: 107 N- and C-terminal truncations and cysteine deletions CD39(aa46-461)_deltacys2 SEQ GO NO: 109 N- and C-terminal truncations and cysteine deletions CD39(aa46-461)_deltacys3 SEQIDNO: 111 N- and C-terminal truncations and cysteine deletions CD39(aa46-461)_deltacys4 SEQIDNO: 113 N- and C-terminal truncations and cysteine deletions CD39(aa46-461)_deltacys5 SEQIDNO: 115 N- and C-terminal truncations and cysteine deletions CD39(aa46461)_dMIL(193204)_delta-cy81 SEQIDNO: 117 N- and C-terminal truncations, central region deletion, and cysteine deletion CD39(aa46461)_dMIL(193204)_delta-cy82 SEQIDNO: 119 N- and C-terminal truncations, central region deletion, and cysteine deletion CD39(aa46461)_dMIL(193204)_delta-cy83 SEQIDNO: 121 N- and C-terminal truncations, central region deletion, and cysteine deletion CD39(aa46461)_dMIL(193204)_delta-cy84 SEQ ID NO: 123 N- and C-terminal truncations, central region deletion, and cysteine deletion CD39(aa46461)_dMIL(193204)_delta-cy85 SEQ ID NO: 125 N- and C-terminal truncations, central region deletion, and cysteine deletion CO39(aa38-476)_delta337-344 SEQ ID NO: 127 N- and C-terminal truncations and cysteine deletions CD39(aa38- 476)_C338A_C343A SEQ ID NO: 129 N- and C-terminal truncations and point mutations by type of cysteine substitution

(b) Microscale expression of hCD39 variants.

293-6E cells (disclosed in WO2006096989A2, incorporated herein by reference) were selected for a microscale experiment as one of the preferred host cell lines for transient expression of proteins in the absence of serum. Transfection was performed using FuGene HD (Roche Applied Science, cat. no. 04709705001) as the transfection reagent. 293-6E cells were cultured as a suspension culture using V3 serum-free culture medium (BioConcept, cat. no. V3-K) for transfection and cell expansion. Cells were grown in Corning shake flasks (Coining, Tewksbury, MA) on an orbital shaker (100-120 rpm) in a humidified incubator at 5% CO ₂ (in flasks containing seed

- 8 046596 culture). For transfection, cells in seed cultures should be maintained in exponential growth phase (cell densities between 5 x 10 ⁵ and 3 x 10 ⁶ /ml) and exhibit >90% viability. Cell densities outside this range result in either a lag phase after dilution or reduced transfection efficiency.

For microscale (0.5 ml) transfections, an aliquot of cells was removed from seed cultures and adjusted to 0.5 x 10 ⁶ cells/ml using serum-free V3 culture medium. A DNA solution (referred to as solution 1) was prepared by diluting 0.5 μg of expression plasmids for hCD39 in 14 μl of V3 serum-free culture medium, then 2.3 μl of FuGene HD solution was also diluted in 14 μl of V3 serum-free culture medium (solution 2). Both solutions were incubated for 5–10 min at room temperature (RT). Solution 2 was then added to solution 1 with gentle mixing and incubated for another 5-15 minutes at room temperature. The transfection mixture was then added to 0.5 ml of cells at a density of 0.5 x 10 ⁶ cells/ml seeded in a 48-well tissue culture plate (Corning, Tewksbury, MA), and the plate was placed on an orbital shaker (300 rpm .) in a humidified incubator at 5% CO ₂ . The culture was harvested 3 days after transfection by centrifugation at 4000 rpm. for 10 minutes at 4°C (Heraeus Multifuge 3 SR, Thermo Scientific, Rockford, IL). The recovered cell culture supernatant was stored at 4°C until further processing.

(c) Western blot analysis of microscale expression supernatant.

Western blot analysis of the microscale expression supernatant was performed to verify the expression and proper production of recombinant hCD39 variants. 8 μl of supernatant was diluted in E-PAGE™ loading buffer (4x, Invitrogen, no. EPBNF-01) and loaded onto 8% E-Page 48 gel (Invitrogen, no. EP04808) under non-reducing conditions. The gel run was performed using a Mother E-Base (Invitrogen) for 23 min, and proteins were transferred to a nitrocellulose membrane (Invitrogen IB301001) using the iBlot system (Invitrogen) according to the manufacturer's instructions (7 min run). After washing 3 times in TBS/0.05 Tween20 (TBST), the membrane was incubated for 1 hour in the presence of 5% milk/TBST with gentle shaking, followed by incubation for 1 hour in the presence of 4 μg/ml anti-mouse APP antibody solution ( an antibody raised against the amyloid precursor protein (APP) peptide fragment used for protein labeling, which is obtained in Novartis's own laboratory), diluted in 2% milk/TBST. After an additional 3 wash steps, the membrane was incubated in the presence of a 1:1000 dilution of alkaline phosphatase-conjugated anti-mouse IgG antibody (Sigma-Aldrich, A5153-1ML) diluted in 2% milk/TBST and washed again 3 times in TBST followed by a step rinsing in TBS. The signal was developed for 1-5 minutes using SIGMAFAST™ BCIP®/NBT (Sigma-Aldrich, no. B5655-25TAB) according to the manufacturer's instructions, and the signal was terminated by rinsing the membrane with water.

(d) Solid phase analysis of AxPaz.

ATPase, ADPase, and AMPase activity patterns were determined using the PiColorLock Gold Phosphate Detection System (Innova Biosciences, cat. no. 303-0030) of plate-immobilized hCD39 variants from microscale expression supernatant (AxPase solid-phase assay). This method was less sensitive than the solution assay (liquid phase AxPase assay) recommended by the manufacturer, but had the potential advantage of reducing AxPase activity mediated by host cell enzymes potentially present in the microscale expression supernatant. 20 μl of anti-mouse APP antibody from a 10 μg/ml solution of antibody (antibody raised against the amyloid precursor protein (APP) peptide fragment used for protein labeling, which is obtained in Novartis's own laboratory) diluted in PBS was added to each well 384 -well transparent MaxiSorp plate (Nunc) and incubated overnight at 4°C. After three washes with TBST, wells were blocked for 1 hour with 100 μl of 5% milk/TBST at room temperature with gentle shaking. After three additional washing steps, 20 μl of microscale expression supernatant serially diluted in 2% milk/TBST was added to the wells in triplicate and incubated for 2 h at room temperature with gentle shaking. The wells were then washed again four times with 100 μl of TBST and twice with 80 μl of 50 mM Tris-Cl/5 mM MgCl ₂ pH 7.5. 30 μl of 80 μM adenosine phosphate solution diluted in 50 mM Tris-Cl/5 mM MgCl ₂ , pH 7.5 (ATP: SIGMA A2383, ADP: SIGMA A2754) was added to each of three replicates and incubated for 24 hours at 37° C. The signal was developed with 7.5 μl of Gold reagent mixture prepared according to the manufacturer's instructions for 10 minutes, and the reaction was stopped with 3 μl of stabilizer. Absorbance readings were read at 620 nm using a TECAN GeniOS Pro instrument.

(2) Results.

(a) Effect of boundaries, membrane interacting loop (MIL) deletion, and cysteine bridge deletion on hCD39 expression level.

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To assess the expression level of different hCD39 variants, the corresponding expression plasmids were introduced by transfection in duplicate into 0.5 ml of 293-6E cells, and Western blotting (with detector Abs to APP) was performed on the supernatant obtained 3 days after transfection. The results are presented in Fig. 2A and FIG. 2B.

The results indicated a higher expression level of hCD39 starting with aa38 compared to aa46. The boundaries of the N-terminal region, as well as the deletion of MIL, did not appear to have a significant effect on the expression level. A higher level of hCD39 expression was also observed with deletion of the first or fourth cysteine bridge in the case of hCD39(aa46-461). The higher level of expression upon deletion of the first cysteine bridge was also confirmed using the hCD39 (aa46-461) AMIL backbone.

(b) Effect of boundaries, membrane interacting loop (MIL) deletion, and cysteine bridge deletion on hCD39 activity.

CD39 enzymatic activity was measured by an AxPase solid-phase assay using the supernatant samples described above. The results are presented in Fig. 3 and fig. 4, as well as in table. 3.

Table 3

Solid phase ATP assay using CD39 variants

Sample Subsequence Average signal Breeding 1/2 Breeding 1/6 Breeding 1/18 Breeding 1/54 Figure 3 hCD39 (aa46461)_deltaCysl SEQ ID NO: 107 0.12755 0.12905 0.13155 0.13545 hCD39 (aa46461)_deltaCys2 SEQ ID NO: 109 0.1287 0.13615 0.12915 0.1375 hCD39 (aa46461)_deltaCys3 SEQ ID NO: 111 0.12265 0.1336 0.13485 0.1365 hCD39 (aa46- SEQ ID NO: 113 0.14 0.1302 0.13535 0.1322

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461)_delta- Cys4 hCD39 (aa46- 461)_delta- Cys5 SEQIDNO: 115 0.1226 0.13865 0.13375 0.13225 hCD39 (aa46461)_deltaM1E_deltaCysl SEQIDNO: 117 0.17695 0.16 0.15755 0.1551 hCD39 (aa46461)_deltaMShdeltaCys2 SEQIDNO: 119 0.1318 0.1419 0.13065 0.1299 hCD39 (aa46461)_deltaMShdeltaCys3 SEQ ID NO: 121 0.13505 0.1376 0.1347 0.13775 hCD39 (aa46461)_deltaMShdeltaCys4 SEQ ID NO: 123 0.21195 0.18745 0.16915 0.14975 hCD39 (aa46461)_deltaMShdeltaCys5 SEQ ID NO: 125 0.1343 0.1486 0.13135 0.10465 hCD39 (aa46- 461) SEQ ID NO: 103 0.30345 0.2433 0.1879 0.1851 hCD39 (aa46- 461)_delta-M1E SEQ ID NO: 105 0.5037 0.3779 0.32345 0.2567 hCD39 (aa38- 476) Sequence ь not shown 0.30745 0.23855 0.18315 0.17295 hCD39 (aa46- 476) SEQ ID NO: 101 0.34815 0.254 0.1975 0.1817 No transfection Figure 4 0.1459 0.14155 0.13855 0.13675 hCD39 (aa38- 476) Sequence not shown 0.45775 0.4007 0.1997 0.14215 hCD39 (aa46- 461 )_delta- MIL SEQ ID NO: 105 0.8983 0.9294 0.6561 0.35405 hCD39 (aa46- 476) SEQ ID NO: 101 0.5756 0.4855 0.27525 0.153 hCD39 (aa46- 461) SEQ ID NO: 103 0.562 0.52455 0.28625 0.15175 hCD39 (aa38476)_delta-M1E (EP28) SEQ ID NO: 4 1.0224 0.9696 0.6263 0.4354 No transfection 0.1483 0.1494 0.158 0.1502

Deletion of MIL appeared to increase the proportion of functionally expressed recombinant CD39 proteins. The different border options did not show any significant effect on the activity of active hCD39. The results indicated significantly reduced or completely eliminated ATPase activity for all cysteine bridge deletion variants. Similar results were obtained in the solid-phase ADPase assay. Thus, it was unexpected that a sequence modification that increased both efficiency and ability to be expressed in

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CD39 was a modification of delta-MIL (AMIL).

3. Example 2: expression marks.

In order to improve the expression properties of the candidates, various expression marks were tested.

Various expression tags based on the N-terminal portion of IL-2 (SEQ ID NO: 131) were tested and are shown in Table 1. 4. The expression tag aa1-16 according to SEQ ID NO: 131 was synthesized at GeneArt.

Table 4

Overview of IL-2-based expression tag options

Reference name GO amino acid sequences GO forward primer sequences GO reverse primer sequences Expression tag aal-16 SEQIDNO: 131 n. O. n. O. Expression tag aal-15 SEQ GO NO: 133 SEQ GO NO: 157 SEQIDNO: 158 aal-6 expression tag SEQ GO NO: 135 SEQIDNO: 159 SEQIDNO: 158 aal-3 expression tag SEQ GO NO: 137 SEQIDNO: 161 SEQ ID NO: 158 aal-9 expression tag SEQIDNO: 139 SEQ GO NO: 162 SEQ ID NO: 158 Expression tag aal-12 SEQIDNO: 141 SEQ ID NO: 163 SEQ ID NO: 158 Expression mark aa4-12 SEQ GO NO: 143 SEQ ID NO: 164 SEQ ID NO: 158

All expression tags were tested against CD39ΔMIL provided under SEQ ID NO: 4. All constructs contain an APP tag and a His tag.

The pRS5a vector shown in FIG. 5 was used for expression. The primer pairs corresponded to those presented in the table. 4.

The annealing temperature was 64°C in all cases.

The PCR solution was prepared by mixing 1 μl of template DNA stock solution with 25 μl of Kara HiFi HotStart polymerase (from Kara Biosystems/KK2602). 1.5 µl of forward primer, 1.5 µl of reverse primer were used and the final volume was adjusted to 50 µl with _H2O .

The PCR reaction was carried out in accordance with the order given in table. 5.

Table 5 ___________________PCR procedure ___________________

Temperature (C°) Time (min.) Cycles Denaturation 94 5 1 Denaturation 94 0.5 35 Annealing 64 1.5 Polymerization 72 0.5 Ultimate polymerization 72 5

After completion of the PCR reaction, DNA extraction was performed using the Wizard® SV Gel and PCR Clean-Up kit, Promega, No. 9282, eluting in 30 μl in 1 column according to the manufacturer's instructions.

The inserts and vector were excised using the enzyme supplied by New England Biolabs (NEB), NruI-HF (NEB #R3192) and NotI-HF (NEB #R3189) in CutSmart(R) buffer. The reaction time was 3 hours at 37°C.

Ligation was performed overnight in the presence of the dephosphorylated vector using the Roche Rapid DNA Dephosphorylation and Ligation Kit No. 04898117001 in accordance with the manufacturer's actual protocol.

The next day, individual colonies were selected for miniature DNA extraction and sequence analysis using forward primer P270 (SEQ ID NO: 165) and reverse primer

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P271 (SEQ ID NO: 166).

In addition, several protein sequences known in the art to increase expression were tested, according to Table. 6.

Table 6

Marks known from the prior art

Reference name Sequence ID Ubiquitin SEQ GO NO 167 C-kappa SEQ GO NO 168 IHSA Domain SEQ GO NO 169 IIHS Domain A SEQ GO NO 170

The resulting test combinations are presented in table. 7.

Table 7

Tested designs

Plasmid name Resulting amino acid sequence pK85a_1b2-leader-APP6-P^-11CO39(aa38- SEQ ID NO: 145

476)_delta-M1E(aa193-204)_8M-optimized pK85a_1E2-leader-118-ubiquitin-11CO39(aa38- SEQ ID NO: 149

476)_delta-M1E(aa193-204)_APP_H18 pK85a_1E2-leader-118-C-kappa-11CO39(aa38- SEQ ID NO: 147

476)_delta-M1E(aa193-204)_APP_H18 pK85a_1E2-leader-H8A-domain1-11CO39(aa38- SEQ ID NO: 151

476)_delta-M1E(aa193-204)_APP_H18 pK85a_1E2-leader-H8A-domainP-11CO39(aa38- SEQ ID NO: 153

476)_delta-M1E(aa193-204)_APP_H18

None of the marks known from the prior art and presented in table. 6 did not provide protein expression (data not shown). This was unexpected since it is known from the prior art that such sequences should enhance expression.

4. Example 3: additional mutations.

In order to improve the characteristics of soluble CD39 and make it suitable for pharmaceutical development, additional modifications were introduced into CD39ΔMIL EP28, shown under SEQ ID NO: 4. Various mutations and variants with mutations are shown in table. 8 and are numbered according to the amino acid positions in wild-type CD39 shown under SEQ ID NO: 1.

Table 8 Point mutations

Abbreviation Number of mutations Regulations e mutations 1 Regulations e mutations 2 Regulations e mutations 3 Regulations e mutations 4 Mutation position 5 ID amino acid relative sequence EP1 1 113: BOM SEQID NO: 6 EP2 2 113: BOM 149: L->M SEQID NO: 8 ERZ 3 113: BOM 304: R->G 469: S->R SEQID NO: 10 EP4 3 95: V->A 113: BOM 469: S->R SEQID NO: 12 EP5 2 149: L->M 441: G->D SEQID NO: 14 EP6 3 104: Y->S 149: L->M 263:W- >R SEQID NO: 16 EP7 4 71: BFU 106: T->S 151: V->A 319: OT SEQID NO: 18

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EP8 1 151: V->A SEQ ID NO: 20 EP9 1 263: W->R SEQ ID NO: 22 ERYU 1 319:1->T SEQ ID NO: 24 ERP 2 113:R->M 319:1->T SEQ ID NO: 26 ERYU 2 276: E->D 319:1->T SEQ ID NO: 28 EP13 2 365: F->S 424: L->P SEQ ID NO: 30 EP14 1 365: F->S SEQ ID NO: 32 EP15 4 292: N->K 365: F->S 424: L->P 463: P->S SEQ ID NO: 34 EP17.1 EP17 EP18 ERYU EP20 EP21 EP22 EP23 EP24 1 2 2 2 2 2 2 4 3 412: Y->F 405: K->N 102: G->D 424: L->Q 276:E->G 113:R->M 276: E->G 113:R->K 412: Y->F 424: L->Q 436: H->D 439: F->S 469: S->R 469: S->G 254: L->M 424: L->Q 263:W- >R 437:I->N 439: F->S 469: S->R SEQ ID NO: 38 SEQ ID NO. 36 SEQ ID No. 40 SEQ ID No. 42 SEQ ID No. 44 SEQ ID No. 46 SEQ ID No. 48 SEQ ID No. 50 SEQ ID No. 52 EP28_8M 8 173: E->D 258: K->R 362: A->N 365: F->Y 404-411: VKEKYLSE -> -QERWLRD SEQ ID No. 145

Two mutations in the active site result in higher activity (365 and 412).

5. Example 4: removal of the glycosylation site.

Using the EP14 variant above, the effect of glycosylation sites was tested by introducing point mutations according to Table. 9, numbered according to amino acid positions in wild-type CD39 shown under SEQ ID NO: 1.

Table 9

Mutations in glycosylation sites

Mutation position Glycosylation site Primer N73Q NDT P928/P929 T229A N.Q.T. P930/P931 N292Q NVS P932/P933 N327Q NTS P934/P935 N371Q NLT P936/P937 N457Q NLT P938/P939

(a) Materials and methods.

The expression vector pRS5a was used for cloning (Fig. 5). The primers presented in Table 1 were used. 10.

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Table 10

Primer sequences

Primers Subsequence Description P928 SEQIDNO: 171 Forward primer to remove the N73Q glycosylation site P929 SEQ GO NO: 172 Reverse primer to remove the N73Q glycosylation site P930 SEQ GO NO: 173 Forward primer for removing the T229A glycosylation site P931 SEQ GO NO: 174 Reverse primer to remove the T229A glycosylation site P932 SEQ GO NO: 175 Forward primer to remove the N292Q glycosylation site P933 SEQ GO NO: 176 Reverse primer to remove the N292Q glycosylation site P934 SEQ GO NO: 177 Forward primer for removing the N327Q glycosylation site P935 SEQ GO NO: 178 Reverse primer to remove the N327Q glycosylation site P936 SEQ GO NO: 179 Forward primer for removing the N371Q glycosylation site P937 SEQIDNO: 180 Reverse primer to remove the N371Q glycosylation site P938 SEQIDNO: 181 Forward primer for removing the N457Q glycosylation site P939 SEQIDNO: 182 Reverse primer to remove the N457Q glycosylation site

PCR was performed using the QuikChange Lightning Site-Directed Mutagenesis Kit (Agilent, no. 210519-5) according to the manufacturer's instructions.

The next day, individual colonies were picked for mini DNA extraction and sequence analysis was performed using forward primer P270 (SEQ ID NO: 165) and reverse primer P271 (SEQ ID NO: 166).

To ensure that the vector backbone was also correct (due to mutagenesis), the sequenced insert fragment was cloned into a new pRS5a vector backbone (Fig. 5) using the following method.

The vector was prepared using the vector backbone of SEQ ID NO: 36 with the expression tag of SEQ ID NO: 135 containing the APP_HIS tag at a stock solution concentration of 3.3 μg/μl.

The vector was digested by mixing 10 μg vector DNA, 0.4 μl HindIII (100 U/μl, NEB), 2 μl EcoRI (20 U/μl, NEB), 5 μl CutSmart buffer at 10x concentration (NEB), H ₂ O to final volume 50 µl. Digestion was carried out for 3 hours at 37°C.

Dephosphorylation was performed using calf intestinal alkaline phosphatase (CIP, NEB, no. M0290L), 10 U/μl. Immediately after digestion, 3 μl of CIP was added to the digested vector and incubated for 30 min at 37°C. The cleaved and dephosphorylated vector was loaded into a preparative 0.8% agarose gel with TAE, and a strip corresponding in size to the ~6100 bp vector was cut out. Purification was performed using the Wizard® SV Gel and PCR Clean-Up kit, Promega, no. 9282, eluting in 100 µl per column. The concentration, determined by OD at 260 nm, was 64 ng/μl.

Digestion of insert fragments with mutations was carried out by mixing 42.5 µl DNA (~ 3-5 µg per DNA), 5 µl CutSmart buffer at 10x concentration, NEB No. B7204S, 0.4 µl HindIIIHF, 100 U/µl, NEB No. R3104S, 2 µl EcoRI-HF, 20 U/µl, NEB No. R3103L, and adjusted to 50 µl

- 15 046596 using H2O. Digestion was carried out for 3 hours at 37°C in a PCR apparatus. The digested inserts were loaded into a preparative 0.8% agarose gel with TAE, and a strip corresponding in size to the vector with ~1400 bp was cut out. Purification was performed using the Wizard® SV Gel and PCR Clean-Up kit, Promega, no. 9282, eluting in 30 µl per column. The concentration, determined by OD at 260 nm, was 1 -25 ng/μl.

Ligation (at a vector:insert ratio of ~1:10) was performed using a rapid DNA ligation kit No. K1423 from Thermo Scientific. 4 μl of 5x ligation buffer was mixed with 1 μl of ligase, 2 μl of HindIII/EcoRI-digested vector fragment at a stock concentration of 64 ng/μl, 13 μl of HindIII/EcoR-digested insert fragment at a stock concentration 1-25 ng/µl. Ligation was carried out for 10 minutes at RT.

Transformation was performed by incubating 10 μl of the ligase mixture with 80 μl of chemically competent XL1Blue cells (Novartis, FS/RL) for 30 min. on ice. Heat shock for 45 seconds at 42°C in an Eppendorf incubator followed by incubation for 2 minutes. on ice. After this, 1 ml of 2YT medium was added, followed by incubation for 1.5 hours at 37°C on an Eppendorf shaker (800 rpm). The cells were centrifuged for 3 minutes at 7000 rpm, and colonies were plated on plates with LB/carbenicillin/glucose followed by overnight incubation at 37°C.

The next day, individual colonies were picked for mini DNA extraction and sequence analysis was performed using forward primer P270 (SEQ ID NO: 165) and reverse primer P271 (SEQ ID NO: 166).

The correct sequences were introduced by transfection into HEK293 cells according to 7 days of expression and 200 ml scale.

The following material was used:

Human embryonic kidney cells constitutively expressing SV40 large T antigen (HEK293-T), e.g. ATCC11268.

Polyethylenimine MAX MW 40000 (PEI) (Polysciences, cat. no. 24765), dissolved in H ₂ O at RT, adjusted to pH 7.05 with NaOH.

Serum-free culture medium M11V3 (BioConcept, Switzerland, cat. no. V3-K).

DNA: obtained using the Qiagen DNA Midiprep kit (#12943) according to the protocol recommended by the supplier.

All cell culture work for transient transfections was performed using suspension culture-adapted HEK293-T cells grown in serum-free M11V3 medium.

Cells were grown in Corning shake flasks (Corning, USA) on an orbital shaker (115 rpm) in a humidified OT incubator at 5% CO2 (in flasks containing seed culture).

The cells used were in the exponential growth phase (cell density from 5x10 ⁵ to 3x10 ⁶ /ml) and had a viability > 90%.

Transfection was carried out on a small scale (in this case 20/50 or 100 µl) using cells, which were counted and the corresponding cell number adjusted to 1.4 x 106 cells/ml using M11V3 medium. A 36% cell suspension was used in the final transfection volume.

A DNA solution (solution 1) was prepared by diluting 1 mg/L of the final volume of DNA in 7% of the final volume of M11V3 and mixing gently. To prevent contamination of cultures due to DNA not subjected to sterilization filtration, penicillin/streptomycin was added to the transfection medium after feeding. The final volume of 3 mg/L PEI solution was then diluted in 7% of the final volume of M11V3 and mixed gently (solution 2). Both solutions were incubated for 5–10 min at room temperature (RT). After this, solution 2 was added to solution 1 with gentle mixing and incubated for another 5-15 minutes at RT. After incubation, the transfection mixture was added to the cells and the culture was cultured for four hours (115 rpm, 37°C, 5% CO ₂ ).

The supernatant was collected after 7 days of expression.

Centrifuged at 4500 rpm, 4°C (Heraeus Multifuge 3 S-R) for 15 min.

Clarified by passing through a sterile 0.22 µm filter (Stericup filter, Thermo Scientific, cat. no. 567-0020).

The supernatant liquid was purified for further steps. 1 mL of supernatant sample was used for IPC on an Open Access APP column.

Sample vials were 2 mL glass crimp vials, Agilent part number 5182-0543, with 11 mm crimp caps, part number 5040-4667.

Protein was purified by immobilized metal ion affinity chromatography (IMAC) on Aekta Pure or Aekta Avant (GE Healthcare) according to the following protocol using a 5 mL HisTrap HP column (GE Life Sciences, order number 17-5248-02). Technical requirements are presented in table. eleven.

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Table 11 IMAC protocol

CV Flow rate (ml/min.) Buffer Balancing 5 5 IMAC A Loading a sample 3 Supernatant liquid cell culture Column washing 10 3 IMAC A Elution 10 3 Gradient 0-20% IMAC B 10 3 100% IMAC B Fractionation Fractions by volume 2 ml

The buffers used were in accordance with the table. 12 and table. 13.

Table 12

IMAC A - balancing and washing buffer

Concentration Chemical compound 10 mM _{Na2HPO4 ​} 10 mM _{NaH2PO4 ​} 500 mM NaCl 20 mM Imidazole (Merck)

Table 13

IMAC B - elution buffer

Concentration Chemical compound 10 mM _{Na2HPO4 ​} 10 mM _{NaH2PO4 ​} 500 mM NaCl 500 mM Imidazole (Merck)

The resulting protein is in accordance with the table. 14 were saved.

Table 14 Designs

Design Mutation positions Cl 140 N73A/F365S S1141 T229A/F365S Cl 142 N292Q/F365S C1143 N334Q/F365S Cl 144 F365S/N371Q C1145 F365S/N457Q C1O58 F365S

(b) Results and interpretation.

No improvement was observed in the properties of the mutant forms in terms of monomer yield and peak during analytical SEC. The parent protein (EP14) with the expression tag according to SEQ ID NO: 137 showed the best yield and the highest peak of monomers in the analysis. The lowest yield, as well as the lowest peak of monomers, was achieved when using the mutant form N371Q.

6. Example 5: combinations.

In order to try to further improve the properties, some of the mutations introduced according to example 3 above were used in combination in accordance with table. 15 shown below. Mutations are numbered according to amino acid positions in wild-type CD39, shown under SEQ ID NO: 1.

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Table 15 Combination of designs

Design Mutation 1 Mutation 2 Mutation 3 Without mutations Primer Y SEQ ID NO: EP14xEP19 365: F->S 424: L->Q 436: H->D P878/P87 9 SEQ ID NO: 64 EP17xEP19 424: L->Q 436: H->D 412: Y->F 405: K->N P88O/P88 1 SEQ ID NO: 70 EP14xEP17 365: F->S 412: Y->F 405: K->N P88O/P88 1 SEQ ID NO: 60 EP10xEP19_N 436D 424: L->Q 436: H->D 319:1->T P882/P88 3 SEQ ID NO: 62 EP 19 without H436D 424: L->Q 436: H->D P884/P88 5 Sequence not included

(a) Materials and methods.

Primers were used in accordance with the table. 16.

Table 16 Primers

Primer Subsequence P878 SEQIDNO: 183 P879 SEQIDNO: 184 P880 SEQIDNO: 185 P881 SEQIDNO: 186 P882 SEQIDNO: 187 P883 SEQIDNO: 188 P884 SEQIDNO: 189 P885 SEQ ID NO: 190

The PCR reaction was carried out using the following pipetting scheme: 5 μl of 10x reaction buffer, μl of double-stranded DNA template (concentration of the initial solution 100 ng/μl),

1.5 µl primer 1,

1.5 µl primer 2, µl dNTP mixture,

1.5 µl QuickSolution reagent,

35.5 µl H ₂ O (to a final volume of 50 µl) and µl QuikChange Lightning enzyme.

The parameters of the PCR cycles were used in accordance with the table. 17.

Table 17 _____________________PCR cycle parameters_______________________

Number of cycles Temperature Time 1 1 96°C 2 minutes. 2 18 96°C 20 s 60°C 10c 68°C 3 min. (30 s/t. o.) 3 1 68°C 6 min.

Immediately after the reaction, 2 μl of the DpnI enzyme was added to each reaction mixture, mixed and incubated for 5 min at 37°C.

Introduction into ultracompetent cells of XL10-Gold by transformation was carried out as follows. Cells were thawed on ice. We used 45 μl per transformation and added 2 μl of BME to each vial. Then, 3 μl of the DpnI-digested PCR product was added and incubated for 30 min. On ice in 15 ml BD tubes. The samples were then heat shocked for 40 seconds and incubated on ice for 2 minutes. 950 μl of SOC medium was then added, followed by incubation for 1.5 h at 37°C in a shaker-incubator. Finally,

- 18 046596 cells were plated on LB/carbenicillin plates and incubated overnight at 37°C. The next day, individual colonies were selected for DNA isolation in mini-quantities and sequence analysis.

The correct sequences were introduced by transfection into HEK293 cells as described in Example 4.

The protein was purified using immobilized metal ion affinity chromatography (IMAC) as follows. 95 ml of supernatant was used (~4 ml of the total volume was retained for analysis (IPC)).

Material used.

Nickel-NTA agarose, Qiagen, cat. No./ID: 30230, Poly-Prep chromatography columns, blank, BioRad, No. 731-1550, IMAC A buffer, pH 7.4 (containing 20 mM NaPO ₄ buffer and 50 mM imidazole). IMAC Buffer B, pH 7.4 (containing 20 mM NaPO4 buffer and 300 mM imidazole). TBS (at 10x concentration, diluted to 1x concentration with MilliQ water). Centrifugal filter unit Amicon Ultra-4 with Ultracel-10 membrane, 10K, UFC801096.

Stages of the process.

1. Column preparation using 1 ml Nickel-NTA agarose from Qiagen (= 0.5 ml CV).

2. Balancing with 10 CV IMAC A.

3. Load 15/45 ml SN into the column (collect material flowing through the column).

4. Wash with 10 CV IMAC A (collection in a 15 ml Falcon tube).

5. Elution in 6.5 CV IMAC B.

6. Determination of eluate concentration.

7. Concentrate 3.5 ml sample to ~400 µl using an Amicon Ultra-4 10K centrifugal filter unit.

8. Buffer exchange by adding TBS and centrifugation at 5000.

Samples were analyzed by analytical SEC using 40 μL of each sample and using a protein gel with 12 μL of each sample.

The resulting protein was saved.

(b) Results and interpretation.

The results are shown in table. 18.

Table 18 _________________________Overview of results_________________________

Name Yield (mg/l) IPC (APP, mg/l) Aggregation (% monomer peak) EP14xEP19 6.85 4.5 75.1 EP17xEP19 13.35 11.5 68.9 EP14xEP17 17.27 11.5 69.2 EP10xEP19_H436D 7.42 4.3 74.3 EP19 without N436O 8.28 2.5 55.6 EP1xEP17 13.46 13.2 77.4 EP28 7.8 2.8 57.5

Protease sites.

No/very low yield was observed when inserting the matriptase site. When using the site for furin, ~40% yield was observed (but at the same time, only 50% of the DNA was used for transfection, since it was a cotransfection with the plasmid encoding furin).

IL2 truncations.

All truncations containing aa1-3 produced comparable results, and the result for aa1-3 individually may have been slightly lower compared to the others, but this could be due to variation between samples. Truncation of aa4-12 resulted in a lack of protein expression. No differences were found between the truncations in EP28, which, like all other EP variants, contained a TSS linker between the IL2 seed sequence and the hCD39 protein.

Combinations.

Combinations with EP19 (L424Q) did not significantly improve protein expression.

Combinations with EP1 (R113M) showed lower levels of aggregation in analytical SEC. NEG726 was well expressed but exhibited the worst aggregation performance of all variants tested (~37%). The EP14xEP17 combination did not result in any additional improvement (F365S+Y412F).

7. Example 6: Cloning of final candidates.

Selected clinical candidates presented in Table. 19 below were expressed for additional testing.

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Table 19

Review of final candidates

Construction AND I Combination of clones Leader IL2 sequence Main subsequence 1 EP1xEP14xEP19aa1-3 SEQ GO NO: 137 SEQ GO NO: 233 2 EP1xEP17xEP19aa1-3 SEQ GO NO: 137 SEQIDNO: 217 3 EP14aa1-3 SEQ GO NO: 137 SEQ ID NO: 229 4 EP17aa1-3 SEQ GO NO: 137 SEQ ID NO: 237 5 EP19aa1-3 SEQ GO NO: 137 SEQ ID NO: 243 6 EP28aa1-3 (leader/ SEQ GO NO: 137 SEQ ID NO: 58 original) 7 EP1xEP14xEP19aa1-6 SEQIDNO: 135 SEQ ID NO: 235 8 EP1xEP17xEP19aa1-6 SEQIDNO: 135 SEQIDNO: 219 9 EP14aa1-6 SEQIDNO: 135 SEQIDNO: 231 10 EP17aa1-6 SEQIDNO: 135 SEQ ID NO: 239 eleven EP19aa1-6 SEQIDNO: 135 SEQ ID NO: 245 12 EP28aa1-6 (leader/initial) SEQIDNO: 135 SEQ ID NO: 80

The following primers were used.

Table 20 Primers

Primer Subsequence R113M, matrix SEQIDNO: 191 RI 13M, straight SEQ GO NO: 192 R113M, reverse SEQ GO NO: 193 F330S, matrix SEQ ID NO: 194 F330S, straight SEQ ID NO: 195 F330S, reverse SEQ ID NO: 196 Y377F, matrix SEQ ID NO: 197 L389C, matrix SEQ ID NO: 198 Y377F/L389Q, matrix SEQ ID NO: 199 Straight SEQ ID NO: 200 Back SEQ ID NO: 201 W.T. SEQ ID NO: 202

The PCR reaction was carried out using the following pipetting scheme: 0.25 μl DMSO, 20 ng vector,

1.5 µl insert (45 ng/µl), µl 5x HF buffer,

0.1 µl Phusion polymerase,

0.08 µl dNTP mixture,

10 µl ddH ₂ O.

The parameters of the PCR cycles were used in accordance with the table. 17.

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Table 21 PCR cycle parameters

Number of cycles Temperature Time 1 1 98°С 3 min. 2 25 98°С 30 s 60°C 30 s 72°C 5 minutes. 46 s 3 1 72°C 10 min.

Immediately after the reaction, 0.5 μl of the DpnI enzyme was added to each reaction mixture, mixed and incubated for 2 hours at 37°C.

Introduction into ultracompetent cells of XL10-Gold by transformation was carried out as follows. Cells were thawed on ice. We used 45 μl per transformation and added 2 μl of BME to each vial. Then, 3 μl of the DpnI-digested PCR product was added and incubated for 30 min. on ice in 15 ml BD tubes. The samples were then heat shocked for 40 seconds and incubated on ice for 2 minutes. 950 μl of SOC medium was then added, followed by incubation for 1.5 h at 37°C in a shaker-incubator. Finally, cells were plated on LB/carbenicillin plates and incubated overnight at 37°C. The next day, individual colonies were selected for DNA isolation in mini-quantities and sequence analysis.

All constructs were subcloned into the genetic environment of the new vector to ensure correct sequences. To do this, all constructs were amplified by PCR with the insertion of G4S linkers and followed by digestion with HindIII/EcoRI.

The resulting protein was saved.

8. Example 7: obtaining proteins for comparison.

(1) Null mutations.

To generate negative control proteins for in vivo studies, one/two mutations were inserted into the parental human CD39ΔMIL protein (EP28). These mutations, as described in the literature, eliminated or reduced the enzymatic activity of this protein. The mutations were located at positions E174A and S218A.

The following primers were used.

Table 22

The PCR reaction was carried out using the following pipetting scheme: 5 μl of 10x reaction buffer, μl of double-stranded DNA template (concentration of the initial solution 100 ng/μl),

1.5 µl primer 1,

1.5 µl primer 2, µl dNTP mixture,

1.5 µl QuickSolution reagent,

35.5 µl H ₂ O (to a final volume of 50 µl) and µl QuikChange Lightning enzyme.

The parameters of the PCR cycles were used in accordance with the table. 17.

Table 23

PCR cycle parameters

Number of cycles Temperature Time 1 1 96°С 2 minutes. 2 18 96°С 20 s 60°C Yus 68°С 3 min. (30 s/t.o.) 3 1 68°С 6 min.

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Immediately after the reaction, 2 μl of the DpnI enzyme was added to each reaction mixture, mixed and incubated for 5 min at 37°C.

Introduction into ultracompetent cells of XL10-Gold by transformation was carried out as follows. The cells were thawed on ice. We used 45 μl per transformation and added 2 μl of BME to each vial. Then, 3 μl of the DpnI-digested PCR product was added and incubated for 30 min. on ice in 15 ml BD tubes. The samples were then heat shocked for 40 seconds and incubated on ice for 2 minutes. 950 μl of SOC medium was then added, followed by incubation for 1.5 h at 37°C in a shaker-incubator. Finally, cells were plated on LB/carbenicillin plates and incubated overnight at 37°C. The next day, individual colonies were selected for DNA isolation in mini-quantities and sequence analysis.

The correct sequences were introduced by transfection into HEK293 cells according to the following protocol.

Digestion buffer was prepared using 10 μg vector DNA, 0.4 μl HindIII (100 U/μl, NEB), 2 μl EcoRI (20 U/μl, NEB), 5 μl CutSmart buffer at 10x concentration (NEB) and H ₂ O to a final volume of 50 µl. The digestion reaction was carried out for 3 hours at 37°C.

Immediately after cleavage, a dephosphorylation reaction was carried out. Calf intestinal alkaline phosphatase (10 U/μl, CIP, NEB, no. M0290L) was added (3 μl) to the digested vector mixture and incubated for 30 min at 37°C.

The digested and dephosphorylated vector was subcloned for sequence verification.

The correct sequences were introduced by transfection into HEK293 cells according to the following protocol.

Expression for 7 days was carried out using the following material: 1. Human embryonic kidney cells constitutively expressing SV40 large T antigen (HEK293-T, ATCC11268); 2. Polyethylenimine MAX MW 40000 (PEI) (Polysciences, cat. no. 24765).

The PEI solution was prepared by thoroughly dissolving 1 g of PEI in 900 mL of cell culture water at room temperature (RT). It was then neutralized with NaOH to obtain a final pH of 7.05. Finally, the volume was adjusted to 1 L and the solution was filtered through a 0.22 µm filter, aliquoted and frozen at -80°C until further use. A thawed aliquot can be refrozen up to 3 times at -20°C, but should not be stored at -20°C for long periods.

Serum-free culture medium M11V3 (BioConcept, Switzerland, cat. no. V3-K).

All cell culture work for transient transfections was performed using suspension culture-adapted HEK293-T cells grown in serum-free M11V3 medium.

To perform transfection on a small scale (<5 L), cells were grown in Corning shake flasks (Corning, USA) on an orbital shaker (100 rpm) in a humidified CO2 incubator at 5% CO2 (in seed culture flasks).

As a rule, cells in seed cultures should be in the exponential growth phase (at a cell density of 5x10 ⁵ to 3x10 ⁶ /ml) and have a viability > 90%. Cell densities outside this range result in either a lag phase after separation or reduced transfection efficiency.

To perform transfection on a small scale (in this case 2 L), an aliquot of cells was removed from the seed cultures and adjusted to 1.4 x 10 ⁶ cells/ml in 36% of the final volume of M11V3 medium.

A DNA solution (solution 1) was prepared by diluting 1 mg/L of the final volume of DNA in 7% of the final volume of M11V3 and mixing gently. To prevent contamination of crops, this solution can be filtered using a 0.22 µm filter (eg Millipore Stericup). In this case, due to the small volume, sterilizing filtration was not performed. The final volume of 3 mg/L PEI solution was then diluted in 7% of the final volume of M11V3 and mixed gently (solution 2). Both solutions were incubated for 5–10 min at room temperature (RT). After this, solution 2 was added to solution 1 with gentle mixing and incubated for another 5-15 minutes at RT (do not stir again during incubation, since PEI coats/condenses the DNA in the form of positively charged particles that bind to the anionic residues of the cell surface and are transported into the cell via endocytosis). After incubation, the transfection mixture is added to the cells and the culture is cultured for four hours (10 rpm, 37°C, 6% CO ₂ ).

Finally, the culture is fed with the remaining 50% of the final volume of M11V3 medium according to the following example. Inoculation volume: 36 ml at 1.4 x 10 ⁶ cells/ml.

Solution 1: 7 ml M11V3 medium with 100 µg plasmid DNA. Solution 2: 7 ml M11V3 medium with 300 µg PEI (300 µl).

Refill: 50 ml M11V3, total volume 100 ml.

The protein was purified using affinity chromatography on immobilized metal ions

- 22 046596 (IMAC) in accordance with the following. 95 ml of supernatant was used (~4 ml of the total volume was retained for analysis (IPC)).

Material used.

Nickel-NTA agarose, Qiagen, cat. No./ID: 30230, Poly-Prep chromatography columns, blank, BioRad, No. 731-1550, IMAC A buffer, pH 7.4 (containing 20 mM NaPO ₄ buffer and 50 mM imidazole). IMAC Buffer B, pH 7.4 (containing 20 mM NaPO ₄ buffer and 300 mM imidazole). TBS (at 10x concentration, diluted to 1x concentration with MilliQ water). Centrifugal filter unit Amicon Ultra-4 with Ultracel-10 membrane, 10K, UFC801096.

Stages of the process.

1. Column preparation using 1 ml Nickel-NTA agarose from Qiagen (= 0.5 ml CV).

2. Balancing with 10 CV IMAC A.

3. Load 15/45 ml SN into the column (collect material flowing through the column).

4. Wash with 10 CV IMAC A (collection in a 15 ml Falcon tube).

5. Elution in 6.5 CV IMAC B.

6. Determination of eluate concentration.

7. Concentrate 3.5 ml sample to ~400 µl using an Amicon Ultra-4 10K centrifugal filter unit.

8. Buffer exchange by adding TBS and centrifugation at 5000.

Samples were analyzed by analytical SEC using 40 μL of each sample and using a protein gel with 12 μL of each sample.

The resulting protein was saved.

(2) Protein with MIL.

Cloning of EP14aa1-3 with a membrane-interacting loop (aa193-204) and PCR with overlapping primers were performed.

The following primers were used.

Table 24 __________________________Primers__________________________

Primer Subsequence Straight SEQ ID NO: 207 Back SEQ ID NO: 208 Reverse for semantic thread SEQ ID NO: 98

The PCR reaction was set up using the following pipetting scheme: 1.2 µl Phusion Hot Start polymerase, µl 5x HF buffer,

0.96 µl 100 mM dNTP (25 mM each dNTP),

0.6 µl forward primer,

0.6 µl reverse primer,

92.64 µl of H ₂ O treated with DEPC.

The parameters of the PCR cycles were used in accordance with the table. 17.

Table 25

PCR cycle parameters

Number of cycles Temperature Time 1 1 98°C 30 s 2 thirty 98°C 10 s Gradient 50-70°C 30 s 72°C 30 s 3 1 72°C 10 min.

Immediately after the reaction, 2 μl of the DpnI enzyme was added to each reaction mixture, mixed and incubated for 2 hours at 37°C.

Transformation was performed by transferring 2 μl of the PCR product into a 96-well PCR plate and cooling on ice. Add 20 µl of chemically competent STELLAR bacteria and mix gently by pipetting up and down once. Samples were incubated for 30 min on ice and then incubated for 45 s at 42°C in a PCR apparatus, then incubated again for 60 s on ice. Finally, 90 μl of SOC medium was added and incubated for 1 hour at 37°C. The entire transfection mixture was plated on LB/ampicillin or LB/carbenicillin plates and grown overnight at 37°C.

The resulting EP14 MIL protein with the amino acid sequence according to SEQ ID NO: 155 was retained.

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9. Example 8: Enzyme activity.

The candidates obtained in the previous examples were characterized by enzyme activity assays.

The following reagents were used: Pi-free buffer, phosphate-free saline (140 mM NaCl, 5 mM KCl, 1 mM MgC12, 2 mM CaCl ₂ , 10 mM Hepes, pH 7.4); and Pi-free buffer + 2% BSA, phosphate-free saline with 20 mg/ml BSA; CD39 protein (according to SEQ ID NO: 1); ATP.

CD39 solution was prepared in duplicate at a concentration of 2 μg/ml. Duplicate ATP solution was prepared at a concentration of 1000 mM from 15 μL of ATP stock solution + 1185 μL buffer, and its total volume was 1.2 mL.

The enzymatic reaction was studied by mixing 60 μl of ATP with 60 μl of CD39 or 60 μl of Pi-free buffer as a control in 48-well PCR plates filled with 120 μl of final solution/well. The final concentration was 500 μM for ATP and 1 μg/ml for CD39.

Samples were incubated at 37°C for 0, 5, 15, 30, 60, 90 and 150 minutes, respectively. The samples were then evaluated using Pi release assay or HPLC.

(1) Pi release assay.

(a) Materials and methods.

Reagents were prepared using a standard Pi detection kit according to the manufacturer's instructions.

A calibration curve for Pi was obtained by dilution in water. A serial dilution of 1:2 of the initial solution of Pi (100 μM) was obtained: 450 μl + 450 μl of water. The concentration according to the calibration curve was 50 μM/25 μM/12.5 μM/6.25 μM/3.1 μM/1.5 μM/0 μM.

A mixture of Gold reagents was obtained: 4 ml of Gold reagent + 40 μl of accelerator (for 3 plates). In a 96-well plate, samples were diluted 1:10 in H2O (dilution in water: 10 µl sample + 90 µl H2O). 50 μl of a 1:10 diluted sample was dispensed into each well of a 96-well half-well plate (Corning, 3690). 12.5 μl of Gold reagent mixture was added to each well (25% of sample volume) and samples were incubated for 10 minutes at room temperature. Absorbance readings were read at 635 nm.

(b) Results and interpretation.

Comparative results for the candidates are shown in Table. 26.

Table 26 Comparative results for candidates

Design I IL-2 seed sequence SEQ ID NO: Exit after ALC % monomers after ALC Melting point (°C) Enzymatic activity in vitro (relative to EP28) 1 EP14aa1-3 SEQ ID NO: 137 SEQ ID NO: 229 33.1 83.8 62 4 2 EP1xEP14aa 1-3 SEQ ID NO: 137 SEQ ID NO: 221 3.7 50.6 65.5 4 3 EP1xEP17aa SEQ ID SEQ ID 95.8 91.9 61 1.5

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1-3 NO: 137 NO: 211 4 EP17xEP19a al-3 SEQ ID NO: 137 SEQ ID NO: 227 3.5 38.9 60.5 1.5 5 EP1xEP17xE Р19аа1-3 SEQ ID NO: 137 SEQ ID NO: 217 153.2 89.7 60.75 1.5 6 EP1aa1-3 SEQ ID NO: 137 SEQ ID NO: 209 6.0 9.2 59.75 1 7 EP1xEP14aa 1-6 SEQ ID NO: 135 SEQ ID NO: 223 148.8 91.8 64 4 8 EP1xEP17aa 1-6 SEQ ID NO: 135 SEQ ID NO: 213 59.4 86.1 59.5 1.5 9 EP17xEP19a al-6 SEQ ID NO: 135 SEQ ID NO: 227 2.7 13.7 60 1.5 10 EP1xEP17xE Р19аа1-6 SEQ ID NO: 135 SEQ ID NO: 219 30.9 88.4 60.75 1.5 eleven EP1xEP17_ K405Naal- 15 SEQ ID NO: 133 SEQ ID NO: 215 156.3 86.4 62.25 1.5 12 EP28aa1-3 SEQ ID NO: 137 SEQ ID NO: 58 2.7 10 60.5 1 13 EP28aa1-16 SEQ ID NO: 131 SEQ ID NO: 72 4.7 45 61.8 1

Enzyme activity was measured by adding 500 μM ATP to the enzyme and analyzing the concentration of ATP, ADP, AMP using HPLC (method description below) over time. The resulting kinetic curves were approximated by the model presented in Fig. 6, to obtain enzyme reaction constants. According to the enzymatic reaction constant Kcat, the enzymes were arranged in the following order (from low activity to high activity): EP28 (wt), EP17, EP14, EP15.

In fig. Figure 7 shows the kinetic data and model fit for EP28. In fig. Figure 8 shows the kinetic data and model fit for EP14. In fig. Figure 9 shows the kinetic data and model fit for EP15.

An overview of enzymatic reaction constants for EP28 (wt), EP14, EP15 and EP17 is shown in Table. 27. Compared with the wild type (WT) variant, the three new variants showed increased catalytic activity. Importantly, the new variants showed a clear increase in catalytic rate constant (kcat) and catalytic efficiency (kcat/Km). Since the reported substrate concentrations of ATP and ADP during tissue injury and thrombosis exceed the reported Km value, this increase in kcat and kcat/Km is likely to translate into higher activity in vivo.

Table 27

Enzymatic reaction constants

ATP -> ADP+P ADP -> AMP+P Inhibition k ^T cat K ^T m k ^T cat/K ^T _M k ^D cat tx M k ^D cat/K ^D _M K d W.T. 65.3 0.7 89.7 40.0 0.1 400.3 0.2 EP14 380.2 1.1 352.6 90.3 Fixed at 0.1 903.0 556.8 EP15 734.9 1.1 658.1 128.7 ο,ι 1287.1 584.9 EP17 180.7 1.0 178.1 67.0 ο,ι 670.0 3.0

(2) HPLC validation analysis (kinetic characteristics and dose response).

(a) Materials and methods.

Candidates were tested using HPLC validation analysis. 70 μL of each sample was transferred into glass vials for HPLC.

Calibration samples were prepared using the 5 mM stock solutions shown in Table. 28.

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Table 28 Stock solutions

5 mM Weight H ₂ O Adenosine 1336.2 µg/ml 1.862 mg 1394 µl Inosine 1341.2 µg/ml 2.668 mg 1989 µl AMR 1736.1 µg/ml 2.182 mg 1257 µl ADP 2506.6 µg/ml 2,500 mg 997 µl Asia-Pacific 2755.7 µg/ml 4.834 mg 1754 µl

1000 μM 20 μL of each stock solution was mixed in an HPLC vial.

500 µM 20 µl 1 mM + 20 µl H ₂ O.

100 µM 10 µl 1 mM+90 µl H2O.

µM 10 µl 100 µM+90 µl H2O.

µM 10 µl 10 µM+90 µl H ₂ O.

HPLC separations were performed using an Agilent 1100 system with capillary pump (G1376A), degasser (G1379A), ALS (G1329A), oven (G1330B), column compartment (G1316A), and DAD (G1315A). Solvent A: 10 mM KH2PO4 (04243, Riedel-de Haen) + 2 mM TBA bromide, pH 7.0 (86857-10G-F, Fluka) and solvent B: 10 mM KH2PO4/ACN 1/1 + 2 mM TBA bromide , pH 5.5. Column: Nucleodur 300-5 C18 EC, 2x150 mm, 5 µm, Macherey-Nagel 760185.20, lot E14100258 36654055. Column temperature was 40°C, injection volume was 10 µl, flow rate was 0.3 ml/min, and gradient represented 0-3': 0% B; 3-23': 0-95% B, linear; 23-28': 95% B, linear; 28-29': 95-0% B, linear; 5' - break time before the next analysis. DAD: 247 nm and 259 nm.

UPLC separation was performed using a Class I UPLC from Waters. Solvent A: 10 mM KH2PO4/10 mM K2HPO4 1/1+2 mM TBA bromide, pH 7.0. Solvent B: 10 mM KH2PO4/ACN 1/1+2 mM TBA bromide, pH 5.5. Column: Fortis Bio C18, 2.1x50 mm, 5 µm, di2chrom BIO318-020301 SN H03161210-2. The column temperature was 40°C, the injection volume was 10 μl, the flow rate was 0.5 ml/min, and the gradient was 0-1': 0% B; 1-8': 0-55% B, linear; 8-10': 55% B; 10-11': 55-0% B, linear; 14' - stop time. DAD operated at 247 nm and 259 nm.

(b) Results.

The results can be seen in Figures 7, 8, 9 and 11, which show kinetic data and model fits for candidates in accordance with various embodiments.

10. Example 9: In vitro activity, initial screening.

The CD39 variants EP1 to EP24 described in the previous examples were cloned into the mammalian expression vector pRS5a_leader_APP_H18 (Fig. 5) without the IL2 leader sequence and without the IL2 start sequence.

(a) Materials and methods.

Small scale expression of EP hits (20/50 ml scale) in HEK293 (PEI transfection) was carried out for 7 days followed by IPC using APP-HPLC (as described above).

Protein purification from 15/45 ml cell culture supernatant using Ni-NTA columns (0.5 ml CV);

Elution with 6 CV IMAC B buffer (20 mM NaPO ₄ buffer, 300 mM imidazole, pH 7.4);

Concentrate and re-buffer the purified protein in TBS, pH 7.4;

Protein analysis using protein gel by analytical SEC;

Delivery of all variants and three controls (original hCD39-dMIL, or EP28, with and without IL2 seed and 8M variant without IL2 seed): 90-200 µl of purified protein in TBS, pH 7.4.

(b) Results and interpretation The results are summarized in Table. 29 below.

All samples were in TBS, pH 7.4, and were labeled APP (SEQ ID NO: 247) and His (SEQ ID NO: 249).

Only the original human CD39ΔMIL (EP28) had a 15 amino acid starting IL2 sequence, aa1-15 (SEQ ID NO: 133).

Pi release assay BOENKTH1-0252824, double detection for 60 and 180 min values.

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Table 29 In vitro activity Pi release assay, 0.25 µg/ml + 500 µM ATP

Date of cleaning Name Concentration [mg/ml] Concentration [micromolar] Total volume [ml] 0 min. Average value after 60 min. Average value after 180 min. 06/17/2016 EP1 0.19 3.7 0.11 10.35 20.90 45.99 06/14/2016 EP2 0.15 2.8 0.10 11.35 23.65 53.92 06/14/2016 ERZ 0.11 2.2 0.10 8.92 19.22 40.76 06/14/2016 EP4 0.25 4.8 0.10 7.99 18.59 37.47 06/14/2016 EP5 0.11 2.1 0.10 17.36 39.59 72.09 06/17/2016 EP6 0.14 2.7 0.15 11.57 32.73 69.63 06/21/2016 EP7 0.41 7.8 0.11 9.47 21.19 43.68 06/21/2016 EP8 0.31 5.9 0.11 7.92 15.23 33.94 06/14/2016 EP9 0.15 2.9 0.10 5.56 13.39 31.38 06/21/2016 ERYU 0.33 6.3 0.11 9.32 21.91 54.07 06/14/2016 EP11 0.23 4.4 0.10 10.24 21.27 46.21 06/21/2016 EP12 0.37 7.1 0.11 10.55 21.99 50.80 06/21/2016 EP13 0.13 2.5 0.11 4.93 3.13 3.54 06/21/2016 ERI 0.34 6.5 0.11 19.07 66.35 104.80 06/14/2016 EP15 0.19 3.7 0.10 11.11 29.26 89.92 06/14/2016 EP17 0.28 5.3 0.10 12.49 30.30 102.81 06/14/2016 EP18 0.15 2.9 0.10 3.91 9.70 23.49 06/17/2016 ERYU 0.55 10.6 0.12 14.36 26.38 69.93 06/14/2016 EP20 0.14 2.7 0.10 3.36 2.22 3.60 06/14/2016 EP21 0.22 4.2 0.10 7.17 16.37 24.27 06/17/2016 EP22 0.17 3.3 0.11 8.06 15.33 37.30 06/21/2016 EP23.1 0.28 5.4 0.11 12.62 23.58 62.78 06/17/2016 EP24 0.10 2.0 0.19 3.10 3.45 4.83 Original 06/14/2016 EP25 hCD39- 0.23 4.4 0.10 4.98 11.46 24.30 dMIL 06/17/2016 EP26 hCD39- 8M 0.19 3.7 0.15 3.66 8.41 24.15 Original 06/17/2016 EP28-IL2initial- 2.19 42.0 0.14 10.25 23.48 52.73 hCD39 06/21/2016 EP1repeated 0.49 9.5 0.11 10.03 17.84 40.33 06/17/2016 EP2repeated 0.55 10.6 0.12 12.80 28.22 66.88 06/17/2016 ERZrepeated 0.56 10.8 0.12 18.05 33.35 79.53 06/17/2016 EP4repeat 0.61 11.7 0.16 15.98 29.47 68.39 06/17/2016 EP5repeat 0.66 12.6 0.15 25.53 46.10 91.32 06/21/2016 EP23.4 0.29 5.5 0.11 10.43 22.45 56.53

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11. Example 10: in vitro activity, refined screening.

A subset of 12 mutant forms was tested a second time, but with the initial IL-2 sequence allowing for a larger scale of expression.

(a) Materials and methods.

The mammalian expression vector pRS5a_leader_APP_His with the initial IL2 sequence of 15 amino acids in length is aa1-15 (SEQ ID NO: 133) (Fig. 5). Expression of EP hits on a small scale (50/100 ml scale) in HEK293 (transfection using PEI) for 7 days followed by IPC using APP-HPLC (as described above).

Protein purification from 45/95 ml cell culture supernatant using Ni-NTA columns (0.5 ml CV).

Elution with 6 CV IMAC B buffer (20 mM NaPO ₄ buffer, 300 mM imidazole, pH 7.4).

Concentrate and re-buffer the purified protein in TBS, pH 7.4.

Protein analysis using protein gel by analytical SEC.

Delivery of all variants and control (parent hCD39-dMIL, or EP28, with IL2 seed sequence aa1-15 (SEQ ID NO: 133)):

500 µl of purified protein in TBS, pH 7.4.

(b) Results and interpretation.

The results are summarized in table. 30, tab. 31 and table. 32 below.

Table 30

Protein purification for hits EP 07/06/2016, part 1

Name Concentration [mg/ml] Concentration [micromolar] Total volume [ml] Yield/46 or 16 ml [mg] Yield (mg/l) IPC (APP, mg/l) EP2 0.64 12.3 0.5 0.32 7.13 6.9 ERZ 0.72 13.9 0.5 0.36 8.02 8.6 EP4 0.86 16.4 0.5 0.43 9.49 8.6 EP5 0.89 17.0 0.5 0.44 9.84 10.1 EP6 0.40 7.7 0.5 0.20 4.46 4.3 EP9 0.57 11.0 0.5 0.29 6.35 6.0 ERP 0.74 14.2 0.5 0.37 8.18 8.3 EP12 0.85 16.3 0.5 0.42 9.40 8.2 EP14 0.82 15.7 0.5 0.41 9.09 7.8 EP17 0.94 18.0 0.5 0.47 13.04 13.3 EP18 0.70 13.4 0.5 0.35 7.75 6.4 EP24 0.65 12.4 0.5 0.32 8.99 10.8 EP28 with initial sequence IL2 0.27 5.2 0.5 0.14 9.01 6.6

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Table 31

Protein purification for hits EP 07/06/2016, part 2

Name Volume expression (ml) Aggregation (%) (Analytical SEC) Peak monomers (%) (Analytical SEC) Destruction (%) (Analytical SEC) Pi assay: 1 µg/ml enzyme, 500 µM ATP, 60 min. (1:10) EP2 50 15.7 69.5 14.9 53,572 ERZ 50 14.9 67.6 17.5 62.6725 EP4 50 11.3 72.5 16.3 52.1195 EP5 50 15.1 67.8 17 75.1995 EP6 50 17.2 59.3 23.5 72,517 EP9 50 21.7 57.5 20.8 63.7175 EP11 50 12.3 72.2 15.6 59.0205 EP12 50 19.9 63.1 17.1 48,358 EP14 50 14.9 66.6 18.5 88.3785 EP17 40 17.3 68.9 13.8 89.8415 EP18 50 15.4 67.2 17.4 61,495 EP24 40 8.9 73 18 74,713 EP28 with initial sequence IL2 20 17.8 56.4 25.8 53.6735

Table 32

Protein purification for hits EP 07/15/2016

Name MW [kDa] E [M-1*cm- 1] Concentration [mg/ml] Concentration [micromolar] Total volume [ml] Quantity delivered Expression volume (ml) EP8 52.08 70875 0.02 0.5 0.5 0.01 50 ERYU 52.08 70875 0.76 14.7 0.5 0.38 50 ERI 52.08 70875 0.21 4.0 0.5 0.10 50 ERI 52.08 70875 0.81 15.6 1 0.81 100 EP17 52.08 70875 0.22 4.3 0.5 0.11 40 ERYU 52.08 70875 1.10 21.2 0.5 0.55 50 EP23 52.08 70875 0.46 8.8 0.5 0.23 50 Control parent EP28 52.08 70875 0.77 14.7 1 0.77 100

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Table 33

Point mutations relative to the wild type CD39 sequence according to SEQ ID NO: 1

Number of mutations Regulations e mutations 1 Regulations e mutations 2 Regulations e mutations 3 Regulations e mutations 4 Found sequence Pi assay: 1 µg/ml enzyme, 500 µM ATP, 60 min, 1:10 1 151: V->A 2x 4,309 1 319:1->T 2x 54,866 1 365: F->S unique 69.0195 4 292: N->K 365: F->S 424: L->P 463: P->S unique 78.81 2 405: K->N 412: Y->F unique 89.415 2 424: L->Q 436: H->D unique 62,912 4 254: L->M 263: W->R 439: F->S 469: S->R unique 88,282

12. Example 11: in vivo activity, pK.

(a) Materials and methods.

To determine PK properties in vivo, 10 mg/kg of the compound at a final concentration of 10 mg/ml in PBS buffer was administered intravenously (1 ml/kg) via the tail vein to 4 conscious female C57BL/6 mice. The mice were obtained from WIGA and their body weight was approximately 22 g. All work with live organisms was carried out in accordance with Swiss animal rights legislation.

Whole blood was collected (50 μL per time point) at 0.25, 3, 8, 24, and 48 hours post-dose in low-volume serum tubes using Minivette POCT. Blood serum was separated and used to determine the concentration.

Gyrolab's technology is an automated nanoliter-scale immunoassay using an affinity flow-through format that is performed through centrifugal forces and laser-induced fluorescence detection. Streptavidin-coated beads were prepacked onto affinity chromatography columns in Gyrolab Bioaffy CD. Each CD contained 112 columns. Affinity capture columns contained 15 nL per microstructure. The injected samples flowed in under the action of capillary effect. The biotinylated capture reagent was bound to streptavidin-coated beads. An analyte solution was then injected, which bound to the capture molecules. Finally, a fluorophore-labeled developing reagent was used. For CD39, the analysis used two different readouts depending on the presence of the APP tag.

1) Anti-CD39 antibody (40035) and anti-APP antibody (27431) are shown in FIG. 10A.

2) Fab (40035) and a 1:1 anti-Fc/anti-CD39 premix (40044) (all EP28aa1-16 constructs) are shown in FIG. 10B. Antibody 40044 loses activity when biotinylated by binding to the amino group; therefore, only antibody 40035 was biotinylated.

All calibration curves for CD39 constructs were diluted in Rexxip A containing 5% (v/v) mouse serum in a 1:2 dilution series. The applicable concentration range for APP-labeled constructs was 5000 ng/mL to 9.77 ng/mL, and for EP28aa1-16 it was 10,000 ng/mL to 9.77 ng/mL. All mouse serum samples were diluted 1:100 in Rexxip A containing 5% (v/v) mouse serum. Samples of CD39 QC constructs were diluted in Rexxip A containing 5% (v/v) mouse serum (50 and 500 ng/ml for APP-tagged constructs and 500 and 1000 ng/ml for EP28aa1-16). The final concentration for all biotinylated capture reagents was 0.1 mg/ml, and the fluorescently labeled detection antibody was diluted to 10 nM in Rexxip F.

(b) Result and interpretation.

The results are summarized in table. 33. As can be seen, all candidates demonstrated the same PK properties. Therefore, the selection of the candidate was not made on the basis of PK properties.

- 30 046596

Table 34

pK values

Design SEQ GO NO: Animal 1 Animal 2 Animal 3 Animal 4 Average t/2 (days) EP28aa1-16 SEQ ID NO: 72 1.1 1.3 1.0 1.1 1.1 EP1xEP14aa1-6 SEQ ID NO: 223 0.9 0.7 0.7 0.3 0.7 EP28aa1-3 SEQ ID NO: 58 0.6 0.7 0.9 0.8 0.8 EP14aa1-3 SEQ ID NO: 229 0.7 1.0 0.6 1.1 0.9 EP14aa1-6 SEQ ID NO: 231 0.7 0.7 0.7 0.8 0.7 EP17aa1-3 SEQ ID NO: 237 0.9 0.8 0.9 0.8 0.9 EP17aa1-15 SEQ ID NO: 241 0.8 0.9 0.9 0.6 0.8

13. Example 12. In vivo activity, AKI model.

(a) Materials and methods.

Nephrectomy of the right kidney was performed before the onset of the clinical I/R situation. The second kidney was removed to avoid the action of compensatory mechanisms that completely change the dynamics of biological processes. Anesthetized, spontaneously breathing animals were placed on the homeothermic blanket of the homeothermic monitoring system and covered with sterile gauze. Body temperature was recorded using a rectal probe and monitored between 36.5 and 37.5°C to avoid hypothermia. Animals were anesthetized, shaved and disinfected (betaseptic). After making a midline incision/laparotomy, the abdominal contents were pushed to the left and the right kidney was removed. The ureter and blood vessels were separated and ligated (9-0 Ethicon), and the kidney was removed.

Induction of I/R injury: Immediately after nephrectomy of the right kidney, the abdominal contents were pushed to the right and the left renal artery was severed to induce renal ischemia.

Microaneurysm clips were used to clamp the vascular pedicle to block blood flow to the kidney and induce renal ischemia. The duration of renal ischemia was counted from the moment the clamp was applied. The occurrence of ischemia was confirmed by a change in the color of the kidney from red to dark purple in a few seconds. After ischemia was induced, the microaneurysm clips were removed, and a change in kidney color to red indicated reperfusion.

(b) Result and interpretation.

The result is shown in Fig. 12. The candidates exhibited a dose-dependent response in vivo that correlated with their specific activity in vitro. In fig. 12A shows the results for the original EP28, FIG. 12B shows the results for EP1xEP17, and FIG. 12C shows the results for EP14. As can be seen, EP28 and EP1xEP17 show similar dose-dependent responses, with EP14, with higher in vitro activity, showing full efficacy at a lower dose.

14. Example 13: title, output and development possibility.

For the purpose of manufacturing selected candidates on a commercial scale, it is important to be able to express them in relatively high yield. For therapeutic proteins, this task may be less straightforward than for therapeutic antibodies due to the complexity of the format in addition to the lack of enrichment technology that allows for the selection of high-yielding clones.

Both candidates, EP14aa1-3 and EP28aa1-3, had comparable technical characteristics that presented a challenge. In particular, low expression titers of earlier expression batches (data not shown) affect production costs or may be even lower after scale-up because control of host cell proteins is not reliable.

In order to attempt to improve protein expression through early clonal selection, both candidates required the development of a customized purification method. For this purpose, cell pools were obtained

- 31 046596 expressing candidates EP28aa1-3 and EP14aa1-3.

The original CHO cell line was used as a host cell line to generate a cell line expressing EP28aa1-16/EP14aa1-3. The host cell line was derived from the CHOK1 cell line, well known to one skilled in the art, in a manner described, for example, in patent applications WO2015092737 and WO201509273 5, both of which are incorporated herein by reference in their entirety. One vial of the CHO line was used to generate a recombinant cell line expressing EP28aa1-16/EP14aa1-3.

The cells were grown in a culture medium with a specific chemical composition. For each transfection, one μg of plasmid DNA linearized with the Swal expression vector encoding EP28aa1-16/EP14aa1-3 was added. The transfection reaction was carried out in a culture medium with a specific chemical composition.

Transfections were performed by electroporation using the AMAXA Gene Pulser system according to the manufacturer's instructions. The original CHO cells used for transfection were in exponential growth phase with cell viability rates greater than 95%. A total of three transfections were performed using 5 x 10 ⁶ cells for each transfection. Immediately after transfection, cells were transferred into shake flasks containing chemically defined culture medium.

Cell pools were incubated for 48 hours at 36.5°C and 10% CO ₂ before starting the selection process. The selection procedure was carried out using a selectable marker encoded by an expression vector. After 48 h of transfection and growth under low folate conditions, additional selective pressure was applied by adding 10 nM MTX to the chemically defined culture medium. By 21 days after the start of MTX selection, pool populations appeared consisting predominantly of MTX-resistant cells. After the pools were extracted, the cells were frozen. To determine the concentration of EP28aa1-16/EP14aa1-3, standard fed-batch batches were formed in chemically defined culture media. Reverse phase chromatography (RPC) was used to determine product concentration. Pools of CHO cells producing EP28aa1-16/EP14aa1-3 were used for FACS single cell sorting/cell printing procedure to generate individualized clonal cell lines.

15. Example 14: therapeutic use.

Extracellular ATP activating _P2X7R has been found to have a clear association with several diseases, such as increased graft-versus-host disease (Wilhelm et al. Graftversus-host disease is enhanced by extracellular ATP activating P2X7R. Nature Medicine 16:12, pages 14341439 (2010)).

In addition, both in vitro and in vivo studies indicate that CD39 is an apyrase important for cardiovascular function through the regulation of ADP levels. Apyrase is known to inhibit platelet aggregation by metabolizing extracellular ADP.

Human apyrase does not covalently bind to platelets compared to other therapies such as clopidogrel (Plavix™), which irreversibly binds to the ADP receptor on the platelet surface. This allows for faster reversal of therapeutic blockade and therefore a safer approach to the management of patients with excessive platelet activation. This provides a safer approach to the management of patients with excessive platelet activation.

Thus, there is a clear rationale for the therapeutic use of compounds that reduce extracellular ATP levels, such as the compounds of the present invention.

Specific non-limiting examples of therapeutic routes for use of the compounds of the present invention include acute organ injury due to trauma and/or hypoxia, such as acute respiratory distress syndrome (ARDS), lung injury, renal failure, acute kidney injury (AKI), including acute kidney injury after coronary artery bypass grafting, delayed graft function after transplantation (including xenotransplantation) of kidney or other solid organs or vascular disease such as vascular occlusive disease, transplantation and xenotransplantation, treatment of individuals suffering from stroke, coronary artery disease or injury resulting from myocardial infarction, atherosclerosis, arteriosclerosis, embolism, preeclampsia, angioplasty, vascular injury, transplantation, neonatal hypoxic-ischemic encephalopathy, platelet-associated ischemic disorders, including pulmonary ischemia, coronary ischemia and cerebral ischemia, ischemia-reperfusion injury (IRI), thrombotic disorders, including coronary artery thrombosis, cerebral artery thrombosis, intracardiac thrombosis, peripheral arterial thrombosis and venous thrombosis, delayed graft function after transplantation (including xenotransplantation) of the kidney or other solid organs. Other non-limiting examples of therapeutic uses of the compounds of the present invention include treatment of burns or radiation injury, sepsis, improvement of wound healing,

- 32 046596 reduction of bleeding or risk of bleeding, prevention of organ damage, graft-versus-host disease or prevention of graft rejection.

Particularly preferred therapeutic routes for use of the compounds of the present invention are acute kidney injury (AKI), such as acute kidney injury after coronary artery bypass grafting, or sepsis, or rhabdomyolysis. This condition increases patient mortality and there is no standard of care (SoC) for it. The main causes of AKI in the intensive care unit are: sepsis (47.5%), major surgery (34%), cardiogenic shock (27%), hypovolemia (26%) and exposure to nephrotoxic compounds (19%). In addition, AKI is an independent strong risk factor for the development of chronic kidney disease (CKD). Acute kidney injury occurs in 20-30% of patients following major cardiac surgery. Another preferred embodiment relates to the use of the isolated apyrase according to the present invention for the treatment of acute kidney injury associated with cardiac surgery.

In another embodiment, the present invention provides an isolated apyrase according to the present invention for use in the treatment of delayed graft function (DGF), acute respiratory distress syndrome (ARDS), acute myocardial infarction (AMI), traumatic brain injury (TBI)/acute ischemic stroke (AIS) or combinations thereof, often called multiple organ failure (MOF) forms.

16. Acute kidney injury (AKI) is a common complication of sepsis. 28% of patients with sepsis develop AKI. In a further preferred embodiment, the present invention relates to the use of an isolated apyrase according to the present invention for the treatment of acute kidney injury associated with sepsis.

Example 15: Therapeutic compositions.

Therapeutic proteins are typically formulated either in aqueous form, ready for administration, or as a lyophilisate for reconstitution with a suitable diluent prior to administration. The protein can be formulated either as a lyophilisate or as an aqueous composition, such as in pre-filled syringes.

A suitable formulation may be an aqueous pharmaceutical composition or a lyophilisate, which can be reconstituted to provide a solution with a high concentration of the therapeutic protein active ingredient and a low level of protein aggregation for delivery to the patient. High protein concentrations are useful because they reduce the amount of material that must be delivered to the patient (dose). Reduced dose volumes minimize the time it takes to deliver a fixed dose to a patient. The high protein concentration aqueous compositions of the present invention are particularly suitable for subcutaneous administration.

Thus, the present invention provides an aqueous pharmaceutical composition suitable for administration to a subject, for example, for subcutaneous administration, containing a therapeutic protein.

The therapeutic protein can be used as a pharmaceutical composition when combined with a pharmaceutically acceptable carrier. In addition to the therapeutic protein, such a composition may contain carriers, various diluents, fillers, salts, buffers, stabilizers, solubilizers and other materials well known in the art. The characteristics of the vehicle will depend on the route of administration. Pharmaceutical compositions for use in the disclosed methods may also contain additional therapeutic agents for treating the specific target disorder.

17. Example 16: route of administration.

Typically, the proteins of the present invention are administered by injection, for example, intravenously, intraperitoneally or subcutaneously. Methods for carrying out this administration are known to those of ordinary skill in the art. It may also be possible to provide compositions that can be administered topically or orally or that can be capable of permeation through mucous membranes. One skilled in the art will appreciate that any suitable means of administration suitable for the particular route of administration chosen can be used.

Examples of possible routes of administration include parenteral (e.g., intravenous (I.V., or IV), intramuscular (IM), intradermal, subcutaneous (S.C., or SC), or infusion), oral and pulmonary (e.g., inhalation), nasal, transdermal ( local), transmucosal, intra-arterial, continuous infusion and rectal administration. Solutions or suspensions used for parenteral, intradermal or subcutaneous use may contain the following components: a sterile diluent such as water for injection, saline, fixed oils, polyethylene glycols, glycerin, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methylparabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid;

- 33 046596 buffers such as acetates, citrates or phosphates, and agents for regulating tonicity such as sodium chloride or dextrose. The pH can be adjusted using acids or bases such as hydrochloric acid or sodium hydroxide. The drug for parenteral administration may be sealed in ampoules, disposable syringes, or multi-dose vials made of glass or plastic.

Apyrase therapy can be initiated by administering a loading dose of the proteins of the present invention to the subject in need of therapy. By the expression loading dose is meant the initial dose of proteins according to the present invention that is administered to a subject where the dose of administered proteins according to the present invention is in the higher dose range. The loading dose can be administered as a single administration, such as a single infusion in which proteins are given IV, or as multiple administrations, such as multiple infusions in which proteins are given IV, provided that the full loading dose is administered over an approximately 24-hour period (or during the first month if multiple intravenous doses are necessary, depending on the severity of the disease). After administration of the loading dose, the subject is then administered one or more additional therapeutically effective doses of the proteins of the present invention. Subsequent therapeutically effective doses may be administered, for example, according to a weekly dosing schedule or once every two weeks, once every three weeks, or once every four weeks. In such embodiments, subsequent therapeutically effective doses are typically in the lower dose range.

Alternatively, in some embodiments, after administration of a loading dose, subsequent therapeutically effective doses of the protein of the present invention are administered according to a maintenance regimen, wherein a therapeutically effective dose of the proteins of the present invention is administered once a month, once every 6 weeks, once every two month, once every 10 weeks, once every three months, once every 14 weeks, once every four months, once every 18 weeks, once every five months, once every 22 weeks, once every six months, once every 7 months, once every 8 months, once every 9 months, once every 10 months, once every 11 months or once every 12 months. In such embodiments, therapeutically effective doses of the proteins of the present invention are in the lower dose range, particularly if subsequent doses are administered at shorter intervals, for example, once every two weeks to once a month, or higher dose range, particularly when subsequent doses are administered at longer intervals, for example when subsequent doses are administered at intervals of one month to 12 months.

The timing of dosing is typically measured from the day of administration of the first dose of the active compound, which is also known as baseline. However, different treating physicians use different naming methods.

It should be noted that week zero may be called week 1 by some attending physicians, while day zero may be called day one by some attending physicians. Thus, it is possible that different clinicians will designate, for example, a dose to be administered on week 3/day 21, on week 3/day 22, on week 4/day 21, on week 4/on day 22, referring to the same dosing regimen. For purposes of compliance, the first week of dosing will be referred to herein as week 0, with the first day of dosing being referred to as day 1. However, one skilled in the art will appreciate that this naming convention is merely for compliance purposes and should not be construed as limiting , i.e., weekly dosing represents the provision of a weekly dose of protein, regardless of whether the physician refers to a particular week as week 1 or week 2. An example of the dosing schedules provided herein is found in FIG. 1 and 2. It should be understood that the dose does not have to be provided at a precise point in time, for example, a dose that should be administered on or about day 29 could be provided, for example, between day 24 and day 34, e.g. 30, provided that it is provided in the relevant week.

As used herein, the phrase container containing a sufficient amount of protein to permit delivery of [the indicated dose] is used to mean that the container (e.g., vial, pen, syringe) contains a volume of protein (e.g., as part of a pharmaceutical composition) , which can be used to provide the required dose. As an example, if the required dose is 500 mg, then the clinician may use 2 ml from a container that contains a 250 mg/ml protein formulation, 1 ml from a container that contains a 500 mg protein formulation /ml, 0.5 ml from a container that contains a protein-based formulation at a concentration of 1000 mg/ml, etc. In each such case, these containers contain a sufficient amount of protein to enable delivery of the required dose of 500 mg.

As used herein, the phrase formulated in a dosage capable of delivering the [designated dose] by [route of administration] is used to indicate that the pharmaceutical composition can be used to provide the required dose

- 34 046596 protein via a designated route of administration (for example, s. c. or i. v.). As an example, if the required dose for subcutaneous administration is 500 mg, then the clinician may use 2 ml of a protein formulation having a concentration of 250 mg/ml, 1 ml of a protein formulation having a concentration of 500 mg/ml, 0. 5 ml of a protein formulation having a concentration of 1000 mg/ml, etc. In each such case, these protein formulations are at a sufficiently high concentration to permit subcutaneous delivery of the protein. Subcutaneous delivery typically requires delivery of volumes of less than about 2 ml, preferably volumes of about 1 ml or less. However, higher volumes can be delivered over a period of time using, for example, a patch/pump mechanism.

Disclosed herein is the use of a protein for the manufacture of a medicament for the treatment of tissue damage in a patient, wherein the medicament is formulated to be placed into containers, each container having a sufficient amount of protein to enable delivery of at least about 75 mg, 150 mg, 300 mg or 600 mg of protein per dose unit.

Disclosed herein is the use of a protein for the manufacture of a medicament for the treatment of tissue damage in a patient, wherein the medicament is formulated in a dosage capable of systemic delivery (eg, i.v. or s.c. delivery) of 75 mg, 150 mg, 300 mg, or 600 mg. protein per unit dose.

18. Example 17: sets.

The present invention also includes kits for treating a patient with tissue damage (as appropriate) with a protein. Such kits contain a protein (eg, in liquid or lyophilized form) or a pharmaceutical composition containing a protein (described above). Additionally, such kits may contain means for administering the protein (eg, syringe and vial, prefilled syringe, prefilled pen, patch/pump) and instructions for use. The instructions may disclose providing the protein to the patient as part of a specific dosing regimen. Such kits may also contain additional therapeutic agents (described above) for the treatment of psoriasis, for example, for delivery in combination with a sealed protein.

The phrase administration device is used to refer to any available instrument for the systemic administration of a drug to a patient, including, but not limited to, a prefilled syringe, vial and syringe, pen, auto-injector, IV, and i-bag. v. administration, pump, patch/pump, etc. With these items, the patient can self-administer the drug (i.e., self-administer the drug), or the drug can be administered by the patient's caregiver or physician.

Disclosed herein are kits for treating a patient with tissue damage, comprising: a) a pharmaceutical composition containing a therapeutically effective amount of protein; b) means for administering the protein to a patient; and c) instructions for administering the protein subcutaneously to a patient in need thereof.

- 35 046596

Sequence table

Amino acid and nucleotide sequences useful for the practice of the present invention are disclosed in table. 34.

Table 35

Sequences useful for the practice of the present invention

SEQ Number ID Sign Subsequence Human wild-type CD39 SEQ ID NO: 1 Amino acids lots MEDTKESNVKTFCSKNILAILGFSSIIAVIALLAVGLTQNKALPE NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARIITGQEE GAYGWITINYLLGKFSQKTR WFSIVPYETNNQETFGALDLGGA STQVTFVPQNQTIESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVS QEKVTEMMKKFCA QPWEEIKTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWE HIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHSTYVF LMVLFSLVLFTVAIIGLLIFHKPSYFWKDMV CD39 rats

- 36 046596

wild type SEQ ID NO: 2 Amino acids lots MEDIKDSKVKRFCSKNILIILGFSSVLAVIALIAVGLTHNKPLPEN VKYGIVLDAGSSHTNLYIYKWPAEKENDTGVVQLLEECQVKGP GISKYAQKTDEIAAYLAECMKMSTERIPASKQHQTPVYLGATA GMRLLRMESKQSADEVLAAVSRSLKSYPFDFQGAKIITGQEEG AYGWITINYLLGRFTQE QSWLNFISDSQKQATFGALDLGGSSTQ VTFVPLNQTLEAPETSLQFRLYGTDYTVYTHSFLCYGKDQALW QKLAQDIQVSSGGILKDPCFYPGYKKVVNVSELYGTPCTKRFE kklpfnqfqvqgtgdyeqchqsilkffnnshcpysqcafngvf lpplqgsfgafsafyfvmd ffkkmandsvssqekmteitknfcs kpweevkasyptvkekylseycfsgtyilslllqgynftgtsw DQIHFMGKIKDSNAGWTLGYMLNLTNMIPAEQPLSPPLPHSTYI SLMVLFSLVLVAMVITGLFIFSKPSYFWKEAV CD39L3 SEQ ID NO: 3 Aminokis lots QIHKQEVLPPGLKYGIVLDAGSSRTTVYVYQWPAEKENNTGVV SQTFKCSVKGSGISSYGNNPQDVPRAFEECMQKVKGQVPSHLH GSTPIHLGATAGMRLLRLQNETAANEVLESIQSYFKSQPFDFRG AQIISGQEEGVYGWITANYLMGNFLEKNLWHMWVHPHGVETT GALDLGGASTQISFV AGEKMDLNTSDIMQVSLYGYVYTLYTHS FQCYGRNEAEKKFLAMLLQNSPTKNHLTNPCYPRDYSISFTMG HVFDSLCTVDQRPESYNPNDVITFEGTGDPSLCKEKVASIFDFK ACHDQETCSFDGVYQPKIKGPFVAFAGFYYTASALNLSGSFSLD TFNSSTWNFCSQNWSQLPLLLPKFDEVYARSY SANYIYHLFV NGYKFTEETWPQIHFEKEVGNSSIAWSLGYMLSLTNQIPAESPLI RLPIEP EP28 SEQ ID NO: 4 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE

- 37 046596

EIKTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 5 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EPl

- 38 046596

SEQ ID NO: 6 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQHQET pvylgatagmrllrmeseeladrvldvverslsnypfdfqga riitgqeegaygwitinyllgkfsqknqetfgaldlggastqvt fvpqnqtiesp dnalqfrlygkdynvythsflcygkdqalwq klakdiqvasneilrdpcfhpgykkvvnvsdlyktpctkrfem tlpfqqfeiqgignyqqchqsilelfntsycpysqcafngiflppl qgdfgafsafyfvmkflnltsekvsqekvtemmkkfcaqpwe eiktsyagvke kylseycfsgtyilslllqgyhftadswehihfi GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 7 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCATGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC

- 39 046596

CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAG CCACAGCA CC EP2 SEQ ID NO: 8 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQHQET PVYLGATAGMRLLRMESEELADRVMDVVERSLSNYPFDFQGA riitgqeegaygwitinyllgkfsqknqetfgaldlggastqvt fvpqnqtiespd nalqfrlygkdynvythsflcygkdqalwq klakdiqvasneilrdpcfhpgykkvvnvsdlyktpctkrfem tlpfqqfeiqgignyqqchqsilelfntsycpysqcafngiflppl qgdfgafsafyfvmkflnltsekvsqekvtemmkkfcaqpwe eiktsyagvkek ylseycfsgtyilslllqgyhftadswehihfi GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 9 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCATGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGATGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC

- 40 046596

TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAAGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTC AGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCG GCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC ERZ SEQ ID NO: 10 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKGFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLRTPLSHST SEQ ID NO: 11 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCATGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA

- 41 046596

TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAGAATCAGGAAACCTTCGGCGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACA GCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGGGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTG A AGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGCGCACACCTCTGAGCCACAGCA CC EP4 SEQ ID NO: 12 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFAQKVNEIGIYLTDCMERAMEVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA riitgqeegaygwitinyllgkfsqknqetfgaldlggastqvt fvpqnqtiespd nalqfrlygkdynvythsflcygkdqalwq klakdiqvasneilrdpcfhpgykkvvnvsdlyktpctkrfem tlpfqqfeiqgignyqqchqsilelfntsycpysqcafngiflppl qgdfgafsafyfvmkflnltsekvsqekvtemmkkfcaqpwe eiktsyagvkek ylseycfsgtyilslllqgyhftadswehihfi GKIQGSDAGWTLGYMLNLTNMIPAEQPLRTPLSHST SEQ ID DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAAGTACGGCAT

- 42 046596

NO: 13 CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGCGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCATGGAAGTGATCCCCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCAC CGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAGAATCAGGAAACCTTCGGCGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTC GTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCAC CAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG AGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGGACACCTCTGAGCCACAGCA CC EP5 SEQ ID NO: 14 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVMDVVERSLSNYPFDFQGA

- 43 046596

RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQFRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFY FVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWEHIHFI DKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 15 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGATGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG

- 44 046596

AGCACATCCACTTCATCGACAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP6 SEQ ID NO: 16 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGISLTDCMERAREVIPRSQHQETP VYLGATAGMRLLRMESEELADRVMDVVERSLSNYPFDFQGAR IITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVTF VPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQALRQKL AKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEMTL PFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPLQ GDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWEEI KTSYAGVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHIHFIG KIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 17 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTCCCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGATGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGCGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAG TCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC

- 45 046596

AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACG CTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP7 SEQ ID NO: 18 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEEENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLSDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDAVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQFRLY GKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGTGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPP LQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPW EEIKTSYAGVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHIH FIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 19 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGGAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGT CCGACTGCATGGAACGGGCCAGGGAAGTGAT CCCCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGCGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAAATCAGGAAACCTTC CGCCCTGGAC

- 46 046596

CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTG AACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCACCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTC CTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP8 SEQ ID NO: 20 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDAVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 21 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG

- 47 046596

CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATTCCCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGCGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAA GA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGTA AGTTCAGCCAGAAGAATCAGGAAACCTTCGGCGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGA AGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTAGTGAACGTGTCCGACCT GTACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGC CATTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAG CAGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTA CTGCCCCTACAGCCAGTGCGCC TTCAACGGCATCTTCCTGCC ACCTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTT CGTGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCC AGGAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAG CCCTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAAGA GAAGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCT GAGCCTGCTGCTGCA GGGCTACCACTTCACCGCCGATAGCTG GGAGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACG CCGGCTGGACACTGGGCTACATGCTGAATCTGACCAACATG ATCCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAG CACC EP9 SEQ ID NO: 22 Amino acids lots TQNKALPENVKYGIVLDAGS SHTS LYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNAL QFRLYGKDYNVYTHSFLCYGKDQALRQK LAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEMT

- 48 046596

LPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPLQ GDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWEEI KTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWEHIHFIG KIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 23 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGAGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAG TCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA

- 49 046596

cc ΕΡΙΟ SEQ ID NO: 24 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGTGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPP LQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPW EEIKTSYAGVKEKYLSEYCFSG TYILSLLLQGYHFTADSWEHIH FIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 25 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTATGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCACCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG

- 50 046596

TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGG CAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCTTTGAGCACACCTCTGAGCCACAGCA CC EP11 SEQ ID NO: 26 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQHQET pvylgatagmrllrmeseeladrvldvverslsnypfdfqga riitgqeegaygwitinyllgkfsqknqetfgaldlggastqvt fvpqnqtiesp dnalqfrlygkdynvythsflcygkdqalwq klakdiqvasneilrdpcfhpgykkvvnvsdlyktpctkrfem tlpfqqfeiqgtgnyqqchqsilelfntsycpysqcafngiflpp lqgdfgafsafyfvmkflnltsekvsqekvtemmkkfcaqpw eeiktsyagv kekylseycfsgtyilslllqgyhftadswehih figkiqgsdagwtlgymlnltnmipaeqplstplshst SEQ ID NO: 27 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCATGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG

- 51 046596

CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCACCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTG TTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACTAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGT ACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP12 SEQ ID NO: 28 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNDILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGTGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPP LQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPW EEIKTSYAGVKEKYLSEYCFSGTY ILSLLLQGYHFTADSWEHIH FIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 29 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG

- 52 046596

CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAATCAGGAAACCTTTCGGCGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGT GCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGATATCCTGCGGGACCCTTGCT TCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTGT ACAAGACCCCCTGCACCAAGA GATTCGAGATGACCCTGCCC TTCCAGCAGTTCGAGATCCAGGGCACCGGCAATTACCAGCA GTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACTG CCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCACC TCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCGT GATGAAGTTCCTGAACCTGACCAGCGAAGGTGTCCCAGG AAAAAGTGACAGAG ATGATGAAGAAGTTCTGCGCCCAGCCC TGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGAA GTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGAG CCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGGA GCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCCG GCTGGACACTGGGCTACATGCTGAATCTGACCAACATGATCC CCGCCGAGCAG CCCCTGAGCACACCTCTGAGCCACAGCACC EP13 SEQ ID NO: 30 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSG ILSLLPQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST

- 53 046596

SEQ ID NO: 31 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGA AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCCGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP14 SEQ ID NO: 32 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGIS KFVQKVNEIGIYLTDCMERARE VIPRS QHQET

- 54 046596

PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQFRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQ QCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 33 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCTTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGA AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA

- 55 046596

GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGTTACATGCTGAATCTGACCAACATGATC CCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCAC C EP15 SEQ ID NO: 34 Amino acids lots FVPQNQTIES PDNALQFRLYGKDYNVYTHSFLCYGKDQALWQ klakdiqvasneilrdpcfhpgykkvvkvsdlyktpctkrfem tlpfqqfeiqgignyqqchqsilelfntsycpysqcafngiflppl qgdfgafsafysvmkflnltsekvsqekvtemmkkfcaqpwe AGVKEKYLSEYCFSGTYILSLLPQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMISAEQPLSTPLSHST SEQ ID NO: 35 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCGCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAAGGTGTCCGACCT GTACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGC

- 56 046596

CCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCATACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTT CTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCCGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CTCCGCCGAGCAGCCCCTGAGCA CACCTCTGAGCCACAGCA CC EP17 SEQ ID NO: 36 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA riitgqeegaygwitinyllgkfsqknqetfgaldlggastqvt fvpqnqties pdnalqfrlygkdynvythsflcygkdqalwq klakdiqvasneilrdpcfhpgykkvvnvsdlyktpctkrfem tlpfqqfeiqgignyqqchqsilelfntsycpysqcafngiflppl qgdfgafsafyfvmkflnltsekvsqekvtemmkkfcaqpwe nekylsefcfsgtyilslllqgyhftadswehihfi GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 37 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA

- 57 046596

AGTTCAGCCAGAAGAATCAGGAAACCTTTCGGCGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCC TGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGAT TTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAACC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAACGAGA AGTACCTGAGCGAGTTTTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AG CACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP17.1 SEQ ID NO: 38 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEFCFSG ILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 39 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG

- 58 046596

CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCCCCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACT ACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAGAATCAGGAAACCTTTCGGCGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACC CACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCAT CCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA CCTGAGCGAGTTTTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP18 SEQ ID NO: 40 Aminokis lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIDIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ

- 59 046596

GKI QGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 41 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGACATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG C GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGA

- 60 046596

TCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGC ACC EP19 SEQ ID NO: 42 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSG ILSLLQQGYHFTADSWEDIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 43 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC

- 61 046596

CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCAGCAGGGCTACCACTTCACCG CCGATAGCTGG GAGGACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGC CGGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGA TCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGC ACC EP20 SEQ ID NO: 44 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNGILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHIHSI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 45 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT

- 62 046596

GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGGGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCG GCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGA CCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTCCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP21 SEQ ID NO: 46 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLRTPLSHST SEQ ID NO: 47 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCATGGAAGTGATCCCCAGAAGC

- 63 046596

CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAGAATCAGGAAACCTTTCGGCGCCCT GGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCG TGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTC CTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGCGCACACCTCTGAGCCACAGCA CC EP22 SEQ ID NO: 48 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNGILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE

- 64 046596

EIKTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLGTPLSHST SEQ ID NO: 49 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGGGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGTTGAATCTGACCAACATGATC CCCGCCGAGCAGCCCCTGGGCACACCTCTGAGCCACAGCAC C EP23

- 65 046596

SEQ ID NO: 50 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFMCYGKDQALRQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSG ILSLLLQGYHFTADSWEHIHSI GKIQGSDAGWTLGYMLNLTNMIPAEQPLRTPLSHST SEQ ID NO: 51 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTATGTG CTACGGAAAGGACCAGGCTCTGAGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAG TCGTGAACGTGTCCGACCTG TACAAGACCCCCTGTACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC

- 66 046596

CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTCCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGAACACCTCTGAG CCACAGCA CC EP24 SEQ ID NO: 52 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAKEVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSG ILSLLQQGYHFTADSWEHNHF IGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 53 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAAGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC

- 67 046596

TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTC AGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCAGCAGGGCTACCACTTCACCGCCGATAGCTGG GAGCAAACCACTTCAT CGGCAAGATTCAGGGCAGCGACGC CGGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGA TCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGC ACC ΕΡ1χΕΡ17_ K405N SEQ ID NO: 54 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVNEKYLSEFCFSGTYILSL LLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 55 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCATGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC

- 68 046596

GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAATCAGGAAACCTTTCGGCGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCT GCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGAT CCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAACC CTGGGA GGAAATCAAGACCTCTACGCTGGCGTGAACGAGA AGTACCTGAGCGAGTTTTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC ΕΡ1χΕΡ17 SEQ ID NO: 56 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA riitgqeegaygwitinyllgkfsqknqetfgaldlggastqvt fvpqnqtiesp dnalqfrlygkdynvythsflcygkdqalwq KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEFCF SGTYILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST

- 69 046596

SEQ ID NO: 57 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCATGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTTTTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP28aal-3 SEQ ID NO: 58 Amino acids lots APTTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGV VHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQH

- 70 046596

QETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQ GARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQ VTFVPQNQTIESPDNALQFRLYGKDYNVYTHSFLCYGKDQAL WQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRF EMTLPFQQFEIQGIGNY QQCHQSILELFNTSYCPYSQCAFNGIFL PPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQP WEEIKTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWEHI HFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 59 DNA GCCCCTACCACCCAGAACAAGGCCCTGCCCGAGAACGTGAA GTACGGCATCGTGCTGGACGCCGGCTCCTCCAACCTCCCT GTACATCTACAAGTGGCCTGCCGAGAAAGAAAACGACACCG GCGTGGTGCACCAAGTGGAAGAGTGCAGAGTGAAGGGCCCC GGCATCTCAAGTTCGTGCAGAAAGTGAACGAGATCGGCAT CTACCTGACCGACTGCATGGAACGGGCCAGA A ATCAGGAAACCTTTCGGCGCC CTGGACCTGGGCGGAGCCAGCACCCAAGTCACATTCGTGCC CCAGAACCAGACCATCGAGAGCCCCGACAACGCCCTGCAGT TCCGGCTGTACGGCAAGGACTACAACGTGTACACCCACAGC TTTCTGTGCTACGGCAAGGACCAGGCCCTGTGGCAGAAGCT GGCCAAGGACATCCAAGTGGCCTCCAACGAGATCCTGCGGG ACCCCTGCTTCCACC CCGGCTACAAGAAAGTGGTCAACGTGT CCGACCTGTACAAGACCCCTTGCACCAAGAGATTCGAGATG ACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAAC TACCAGCAGTGCCACCAGTCCATCCTGGAACTGTTCAACACC TCCTACTGCCCCTACTCCCAGTGCGCCTTCAACGGCATCTTC CTGCCTCCACTGCAGGGCGACTTCGGCGCCTTCTCCGCCTTC GTGATGAAGTTCCTGAACCTGACCTCCGAGAAAGTG TCCCAGGAAAAAGTGACCGAGATGATGAAGAAGTTCTGCGC CCAGCCCTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGA AAGAGAAGTACCTGTCCGAGTACTGCTTCTCCGGCACCTACA

- 71 046596

TCCTGTCCCTGCTGCTGCAGGGCTACCACTTCACCGCCGACA GCTGGGAGCACATCCACTTCATCGGCAAGATCCAGGGATCC GACGCTGGCTGGACCCTGGGCTACATGCTGAATCTGACCAA CATGATCCCCGCCGAGCAGCCCCTGTCCACCCCTCTGTCTCA CTCCACC EP14xEP17 SEQ ID NO: 60 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEFCFSG ILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 61 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCTTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC

- 72 046596

CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAG TTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTTTTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGTTACATGCTGAATCTGACCAACATGATC CCCGCCGAGCAGCCCCTGA GCACACCTCTGAGCCACAGCAC C EP10xEP19 _H436D SEQ ID NO: 62 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGTGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPP LQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPW EEIKTSYAGVKEKYLSEYCFSG TYILSLLQQGYHFTADSWEDIH FIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 63 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA

- 73 046596

AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAATCAGGAAACCTTCGGCGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGA AGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCACCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTG CGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA CTGCAGCAGGGCTACCACTTCACCGCCGATAGCTGG GAGGACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGC CGGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGA TCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGC ACC EP14xEP19 SEQ ID NO: 64 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSG ILSLLQQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 65 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT

- 74 046596

ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCCCCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCC GACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAATCAGGAAACCTTCGGCGCCTTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCC CTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAG ATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CT GAGGAAATCAAGACCTCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCAGCAGGGCTACCACTTCACCGCCGATAGCTGG GAGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGC CGGCTGGACACTGGGTTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP28aal- 15 SEQ ID NO: 66 Aminokis lots APTSSSTKKTQLTSSTQNKALPENVKYGIVLDAGSSHTSLYIYK WPAEKENDTGVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCM ERAREVIPRSQHQETPVYLGATAGMRLLRMESEELADRVLDVV

- 75 046596

ERSLSNYPFDFQGARIITGQEEGAYGWITINYLLGKFSQKNQETF GALDLGGASTQVTFVPQNQTIESPDNALQFRLYGKDYNVYTHS FLCYGKDQALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVS DLYKTPCTKRFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCP YSQCAFNGIF LPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVT EMMKKFCAQPWEEIKTSYAGVKEKYLSEYCFSGTYILSLLLQG YHFTADSWEHIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLS TPLSHST SEQ ID NO: 67 DNA GCCCCTACCAGCAGCAGCACCAAGAAAACCCAGCTGACCAG CAGCACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACG GCATCGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTAC ATCTACAAGTGGCCTGCCGAAAGAAAACGACACCGGCGT GGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCA TCAGCAAGTTCGTGCAGAAAGTGAACGAGA TCGGCATCTAC CTGACCGACTGCATGGAACGGGCCAGGGAAGTGATCCCCAG AAGCCAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCG CCGGCATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCC GACCGGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTA CCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGA AGAAGGCGCCTACGGCTGGATCACCATCA ACTACCTGCTGG GCAAGTTCAGCCAGAAGAATCAGGAAACCTTCGGCGCCCTG GACCTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAG AATCAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCG GCTGTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCT GTGCTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCA AGGACATCCAGGTGGCC AGCAACGAGATCCTGCGGGACCCT TGCTTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGAC CTGTACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCT GCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCA GCAGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCT ACTGCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGC CACCTCTGCA GGGGGATTTCGGCGCCTTCAGCGCCTTCTACT TCGTGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCC CAGGAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCA GCCCTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAAG

- 76 046596

AGAAGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATC CTGAGCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGC TGGGAGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGA CGCCGGCTGGACACTGGGCTACATGCTGAATCTGACCAACA TGATCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCAC AGCACC EP17xEP19 _H436D SEQ ID NO: 68 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEFCFSG ILSLLQQGYHFTADSWEDIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 69 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC

- 77 046596

TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTC AGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTTTTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCAGCAGGGCTACCACTTCACCGCCGATAGCTGG GAGGACATCCACTTCATCG GCAAGATTCAGGGCAGCGACGC CGGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGA TCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGC ACC EP17xEP19 SEQ ID NO: 70 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEFCFSG ILSLLQQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 71 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA

- 78 046596

TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAGAATCAGGAAACCTTCGGCGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACA GCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTG A ACC EP28aal- 16 SEQ ID NO: 72 Amino acids lots APTSSSTKKTQLTSSGTQNKALPENVKYGIVLDAGSSHTSLYIY KWPAEKENDTGVVHQVEECRVKGPGISKFVQKVNEIGIYLTDC MERAREVIPRSQHQETPVYLGATAGMRLLRMESEELADRVLD VVERS LSNYPFDFQGARIITGQEEGAYGWITINYLLGKFSQKNQ ETFGALDLGGASTQVTF VPQNQTIESPDNALQFRLYGKDYNVY THSFLCYGKDQALWQKLAKDIQVASNEILRDPCFHPGYKKVVN VSDLYKTPCTKRFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSY CPYSQCAFNGIFLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEK VTEMMKKFCAQPWEEIKTSY AGVKEKYLSEYCFSGTYILSLLL QGYHFTADSWEHIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQP

- 79 046596

LSTPLSHST SEQ ID NO: 73 DNA GCCCCTACCTCCTCCAGCACCAAGAAAACCCAGCTGACCTCC AGCGGCACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTA CGGCATCGTGCTGGACGCCGGCTCCTCCCACACCTCCCTGTA CATCTACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCG TGGTGCACCAAGTGGAAGAGTGCAGAGTGAAGGGCCCCGGC ATCTCCAAGTTCGTGCAGAAAGTGAACGAGA TCGGCATCTA CCTGACCGACTGCATGGAACGGGCCAGAGAAGTGATCCCTC GGTCCCAGCACCAGGAAACCCCTGTCTACCTGGGCGCCACC GCCGGCATGCGGCTGCTGCGGATGGAATCCGAGGAACTGGC CGACCGGGTGCTGGACGTGGTGGAACGGTCCCTGTCCAACT ACCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGG AAGAGGGCGCCTACGGCTGGATCAC CATCAACTACCTGCTG GGCAAGTTCTCCCAGAAGAATCAGGAAACCTTCGGCGCCCT GGACCTGGGCGGAGCCAGCACCCAAGTCACATTCGTGCCCC AGAACCAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTC CGGCTGTACGGCAAGGACTACAACGTGTACACCCACAGCTT TCTGTGCTACGGCAAGGACCAGGCCCTGTGGCAGAAGCTGG CCAAGGACATCCAAG TGGCCTCCAACGAGATCCTGCGGGAC CCCTGCTTCCACCCCGGCTACAAGAAAGTGGTCAACGTGTCC GACCTGTACAAGACCCCTTGCACCAAGAGATTCGAGATGAC CCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAACTA CCAGCAGTGCCACCAGTCCATCCTGGAACTGTTCAACACCTC CTACTGCCCCTACTCCCAGTGCGCCTTCAACGGCATCTTCCT GCCT CCACTGCAGGGCGACTTCGGCGCCTTCTCCGCCTTCTA CTTCGTGATGAAGTTCCTGAACCTGACCTCCGAGAAAGTGTC CCAGGAAAAAGTGACCGAGATGATGAAGAAGTTCTGCGCCC AGCCCTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAA GAGAAGTACCTGTCCGAGTACTGCTTCTCCGGCACCTACATC CTGTCCCTGCTGCTGCAGGGCTACCACTTCACCGCCGACAGC TGGGAGCACATCCACTTCATCGGCAAGATCCAGGGATCCGA CGCTGGCTGGACCCTGGGCTACATGCTGAATCTGACCAACAT GATCCCCGCCGAGCAGCCCCTGTCCACCCCTCTGTCTCACTC CACC EPlxEP14x

- 80 046596

EP19 SEQ ID NO: 74 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSGTYI LSLLQQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 75 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCATGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGA AGTTCCCTGAACCTGACCAGCGAGAAGGTGTCCCAG

- 81 046596

GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCAGCAGGGCTACCACTTCACCGCCGATAGCTGG GAGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGC CGGCTGGACACTGGGCTACATGCTGAATCTGACCAA CATGA TCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGC ACC ΕΡ1χΕΡ17χ EP19 SEQ ID NO: 76 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEFCFSGTYI LSLLQQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 77 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCATGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG

- 82 046596

CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTT CAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTT CTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCAGCAGGGCTACCACTTCACCGCCGATAGCTGG GAGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGC CGGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGA TCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGC ACC ΕΡ1χΕΡ14 SEQ ID NO: 78 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 79 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCATGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG

- 83 046596

CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAATCAGGAAACCTTTCGGCGCCTTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGT GCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAG AGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG ACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGTTACATGCTGAATCTGACCAACATGATC C CCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCAC C EP28aal-6 SEQ ID NO: 80 Amino acids lots APTSSSTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDT GVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRS QHQETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPF DFQGARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGA STQVTFVPQNQT IESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEKY LSEYCFSGTYILSLLLQGYHFTADSWE

- 84 046596

HIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 81 DNA GCCCCTACCAGCAGCAGCACCCAGAACAAGGCCCTGCCCGA GAACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCC ACACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAA AACGACACCGGCGTGGTGCATCAGGTGGAAGAGTGCAGAGT GAAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACG AGATCGGCATCTACCTGACCGACTGCATG GAACGGGCCAGG GAAGTGATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGTA TCTGGGAGCCACCGCCGGCATGAGACTGCTGAGAATGGAAA GCGAGGAACTGGCCGACCGGGTGCTGGACGTGGTGGAAAGA AGCCTGAGCAACTACCCATTCGATTTTCAAGGCGCCAGAATC ATCACCGGCCAGGAAGAAGGCGCCTACGGCTGGATCACCAT CAACTACCTGCTGGGCAAGTTCAGC CAGAAGAATCAGGAAA CCTTCGGCGCCCTGGACCTGGGCGGAGCTTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGG CAGAAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGAT CCTGCGGGACCCTTGCTTCC ACCCCGGCTACAAGAAAGTCGT GAACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGAT TCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCA TCGGCAATTACCAGCAGTGCCACCAGAGCATCCTGGAACTG TTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAAC GGCATCTTCCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTC TTCTACTTCGTGATGAAGTTCCTGAACCTGACCAGC GAGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGA AGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTAC GCTGGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCAG CGGCACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTT CACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGA CAGCGACGCCGGCTGGACACTGGGCTACATGCTG AATCTGACCAACATGATCCCCGCCGAGCAGCCCCTGAGCAC ACCTCTGAGCCACAGCACC EP28_E174 A

- 85 046596

SEQ ID NO: 82 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEAGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSG ILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 83 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCACCGGCCAGGAAGC CGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC

- 86 046596

CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAG CCACAGCA CC EP28_E174 A_S218A SEQ ID NO: 84 Aminokis lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEAGAYGWITINYLLGKFSQKNQETFGALDLGGAATQVT FVPQNQTIESPDNAL QFRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSG TYILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 85 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCACCGGCCAGGAAGC CGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTGCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG

- 87 046596

ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGG CATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGC TACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP14_N73 Q SEQ ID NO: 86 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKEQDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDN ALQFRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCF SGTYILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 87 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAACAGGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCCCCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG

- 88 046596

CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAATCAGGAAACCTTTCGGCGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGT GCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAG AGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG ACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCC CGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP14.T229 A SEQ ID NO: 88 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQAIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE

- 89 046596

EIKTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 89 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGGCCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGA AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP14_N292

- 90 046596

Q SEQ ID NO: 90 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVQVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSG TYILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 91 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGCAGGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGA AGTTCCCTGAACCTGACCAGCGAGAAGGTGTCCCAG

- 91 046596

GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACC AACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP14_N327 Q SEQ ID NO: 92 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFQTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSG TYILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 93 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG

- 92 046596

CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGT TCCAGACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGT ACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP14_N371 Q SEQ ID NO: 94 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSAFYSVMKFLQLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSG ILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 95 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCCCCAGAAGC

- 93 046596

CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAGAATCAGGAAACCTTTCGGCGCCCT GGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCG TGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGAAGTTCC TGCAGCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC EP14_N457 Q SEQ ID NO: 96 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL

- 94 046596

QGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWEHIHFI GKIQGSDAGWTLGYMLQLTNMIPAEQPLSTPLSHST SEQ ID NO: 97 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTCCG TGATGA AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGCAGCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC

- 95 046596

SEQ ID NO: 98 Reverse primer FOR semantic thread with MIL TGCCCTACGAGACAAACAATCAGGAAACCTTCGGCGCCCTG GACCTGGGCGGAGCTTCTACCCAAGTGA CD39(aa39 -469) SEQ ID NO: 99 Amino acids lots QNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKTRWFSIVPYETNNQETFGA LDLGGASTQVTFVPQNQ TIESPDNALQFRLYGKDYNVYTHSFL CYGKDQALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDL YKTPCTKRFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYS QCAFNGIFLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEM MKKFCAQPWEEIKTSYAGVKEK YLSEYCFSGTYILSLLLQGYH FTADSWEHIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLS SEQ ID NO: 100 DNA CAGAACAAAGCCCTGCCCGAGAACGTGAAGTACGGCATCGT GCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCTACA AGTGGCCTGCCGAGAAAGAAAACGATACCGGTGTCGTGCAC CAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAGCAA GTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGACCG ACTGCATGGAACGGGCCAGAAGTGATCCCCA GAAGCCAG CACCAGGAAACCCCCGTGTACCTGGGAGCCACAGCCGGCAT GAGACTGCTGCGGATGGAAAGCGAGGAACTGGCCGACAGA GTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCATT CGATTTTCAAGGGGCCAGAATCACCGGCCAGGAAGAGG GCGCTTACGGCTGGATCACCATCAACTACCTGCTGGGCAAGT TCAGCCAGAAAACCCGGTGGTTCAGCATCGTG CCCTACGAG ACAAACAATCAGGAAACCTTCGGAGCCCTGGACCTGGGCGG AGCCTCTACCCAAGTGACCTTCGTGCCCCAGAATCAGACCAT CGAGAGCCCCGACAACGCCCTGCAGTTCCGGCTGTACGGCA AGGACTACAATGTGTACACCCACAGCTTTCTGTGCTACGGAA AGGACCAGGCCCTGTGGCAGAAGCTGGCCAAGGACATCCAG

- 96 046596

GTGGCCAGCAACGAGATCCTGCGGGACCCTTGCTTCCACCCC GGCTACAAGAAAGTCGTGAACGTGTCCGACCTGTACAAGAC CCCCTGCACCAAGAGATTCGAGATGACCCTGCCCTTCCAGCA GTTCGAGATCCAGGGCATCGGCAACTACCAGCAGTGCCACC AGAGCATCCTGGAACTGTTCAACACCAGCTACTGCCCCTACA GCCAGTGCGCCTTCAACGGCATCTTCCTGCCA CCTCTGCAGG GGGACTTCGGCGCTTTCAGCGCCTTCTACTTCGTGATGAAGT TCCTGAACCTGACCAGCGAGAAGGTGTCCCAGGAAAAAGTG ACAGAGATGATGAAGAAGTTCTGCGCCCAGCCCTGGGAGGA AATCAAGACCTCCTACGCTGGCGTGAAAGAGAAGTACCTGA GCGAGTACTGCTTCAGCGGTACCTACATCCTGAGCCTGCTGC TGCAGGGCTACCACTTCACCGCCG ATAGCTGGGAGCACATC CACTTCATCGGCAAGATTCAGGGCAGCGACGCCGGCTGGAC ACTGGGCTACATGCTGAATCTGACCAACATGATCCCCGCCGA GCAGCCCCTGAGC CD39(aa46 -476) SEQ ID NO: 101 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARIITGQEE GAYGWITINYLLGKFSQKTRWFSIVPYETNNQETFGALDLGGA STQVTFVPQNQTIES PDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEKYLS EYCFSGTYILSLLLQGYHFTADSWE HIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 102 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGTGCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA

- 97 046596

GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAACCCGGTGGTT CAGCATCGTGCCCTACGAGACAAACAATCAGGAAACCTTCG GAGCCCTGGACCTGGGCGGAGCCTCTACCCAAGTGACCTTC GTGCCCCAGAATCAGACCATCGAGAGCCCCGACAACG CCCT GCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTACACCC ACAGCTTTCTGTGCTACGGAAAGGACCAGGCCCTGTGGCAG AAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGATCCT GCGGGACCCTTGCTTCCACCCCGGCTACAAGAAAGTCGTGA ACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGATTC GAGATGACCCTGCCCTTCCAGCAG TTCGAGATCCAGGGCATC GGCAACTACCAGCAGTGCCACCAGAGCATCCTGGAACTGTT CAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGG CATCTTCCTGCCACCTCTGCAGGGGGACTTCGGCGCTTTCAG CGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAGCGA GAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGAAG TTCTGCGCCCAGCCCTGG GAGGAAATCAAGACCTCCTACGCT GGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCAGCGG TACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTTCAC CGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGATTC AGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCTGAAT CTGACCAACATGATCCCCGCCGAGCAGCCCCTGAGCACACC TCTGTCTCACAGCA CC CD39(aa46 -461) SEQ ID NO: 103 Aminokis lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARirrGQEE GAYGWITINYLLGKFSQKTRWFSIVPYETNNQETFGALDLGGA STQVTFVPQNQT IESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEKY LSEYCFSGTYILSLLLQGYHFTADSWE

- 98 046596

HIHFIGKIQGSDAGWTLGYMLNLTNM SEQ ID NO: 104 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGTGCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAACCCGGTGGTT CAGCATCGTGCCCTACGAGACAAA CAATCAGGAAACCTTCG GAGCCCTGGACCTGGGCGGAGCCTCTACCCAAGTGACCTTC GTGCCCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCT GCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTACACCC ACAGCTTTCTGTGCTACGGAAAGGACCAGGCCCTGTGGCAG AAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGATCCT GCGGGACCCTTGCTTCC ACCCCGGCTACAAGAAAGTCGTGA ACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGATTC GAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATC GGCAACTACCAGCAGTGCCACCAGAGCATCCTGGAACTGTT CAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGG CATCTTCCTGCCACCTCTGCAGGGGGACTTCGGCGCTTTCAG CTACTTCGTGATGAAGTTCCTGAACCTGACCAGCGA GAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGAAG TTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTACGCT GGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCAGCGG TACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTTCAC CGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGATTC AG GGCAGCGACGCCGGCTGGACACTGGGCTACATGCTGAAT CTGACCAACATG CD39(aa46 461)_dMIL

- 99 046596

(193-204) SEQ ID NO: 105 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARirrGQEE GAYGWITINYLLGKFSQKNQETFGALDLGGASTQVTFVPQNQT IESPDNALQFRLY GKDYNVYTHSFLCYGKDQALWQKLAKDIQ VASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEMTLPFQQFE IQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPLQGDFGAF SAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWEEIKTSYA GVKEKYLSEYCFSGTYILSL LLQGYHFTADSWEHIHFIGKIQGSD AGWTLGYMLNLTNM SEQ ID NO: 106 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGTGCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAAATCAGGAAAC CTTCGGAGCCCTGGACCTGGGC AGCCTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCCCTGTG GCAGAAGCTGGCCAAGCATCCAGGTGGCCAGCAACGAGA TCCTGCGGGACCCTTGCTTCCACCCCGGCTACAAGAAAGTCG TGAACGTGTCCGACCT GTACAAGACCCCCTGCACCAAGAGA TTCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGC ATCGGCAACTACCAGCAGTGCCACCAGAGCATCCTGGAACT GTTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAA CGGCATCTTCCTGCCACCTCTGCAGGGGGACTTCGGCGCTTT CAGCGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAG CGAGAAGG TGTCCCAGGAAAAAGTGACAGAGATGATGAAG

- 100 046596

AAGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTA CGCTGGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCA GCGGTACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACT TCACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAG ATTCAGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCT GAATCTGACCAACATG CD39(aa46 461)_delt a-cysl SEQ ID NO: 107 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEEARVK GPGISKFVQKVNEIGIYLTDAMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARirrGQEE GAYGWITINYLLGKFSQKTRWFSIVPYETNNQETFGALDLGGA STQVTFVPQNQTIES PDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEKYLS EYCFSGTYILSLLLQGYHFTADSWE HIHFIGKIQGSDAGWTLGYMLNLTNM SEQ ID NO: 108 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGGCCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACGCCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAACCCGGTGGTT CAGCATCGTGCCCTACGAGACAAA CAATCAGGAAACCTTCG GAGCCCTGGACCTGGGCGGAGCCTCTACCCAAGTGACCTTC GTGCCCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCT GCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTACACCC

- 101 046596

ACAGCTTTCTGTGCTACGGAAAGGACCAGGCCCTGTGGCAG AAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGATCCT GCGGGACCCTTGCTTCCACCCCGGCTACAAGAAAGTCGTGA ACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGATTC GAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATC GGCAACTACCAGCAGTGCCACCAGAG CATCCTGGAACTGTT CAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGG CATCTTCCTGCCACCTGCAGGGGGACTTCGGCGCTTTCAG CGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAGCGA GAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGAAG TTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTACGCT GGCGTGAAAGAGAAGTACCTG AGCGAGTACTGCTTCAGCGG TACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTTCAC CGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGATTC AGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCTGAAT CTGACCAACATG CD39(aa46 461)_delt a-cys2 SEQ ID NO: 109 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARirrGQEE GAYGWITINYLLGKFSQKTRWFSIVPYETNNQETFGALDLGGA STQVTFVPQNQT IESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPAFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQAHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEKY LSEYCFSGTYILSLLLQGYHFTADSWE HIHFIGKIQGSDAGWTLGYMLNLTNM SEQ ID NO: 110 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGTGCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGAG

- 102 046596

AAGTGATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAAC CCGGTGGTT CAGCATCGTGCCCTACGAGACAAACAATCAGGAAACCTTCG GAGCCCTGGACCTGGGCGGAGCCTCTACCCAAGTGACCTTC GTGCCCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCT GCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTACACCC ACAGCTTTCTGTGCTACGGAAAGGACCAGGCCCTGTGGCAG AAGCTGGCCAAGGACATCCAGGTGG CCAGCAACGAGATCCT GCGGGACCCTGCCTTCCACCCCGGCTACAAGAAAGTCGTGA ACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGATTC GAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATC GGCAACTACCAGCAGGCCCACCAGAGCATCCTGGAACTGTT CAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGG CATCTTCCTGCCACCT CTGCAGGGGGACTTCGGCGCTTTCAG CGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAGCGA GAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGAAG TTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTACGCT GGCGTGAAAGAGAAGTACCTGAGCGGTACTGCTTCAGCGG TACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTTCAC TGGGAGCACATCCACTTCATCGGCAAGATTC AGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCTGAAT CTGACCAACATG CD39(aa46 461)_delt a-cys3 SEQ ID NO: 111 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARirrGQEE GAYGWITINYLLGKFSQKTRWFSIVPYETNNQETFGALDLGGA STQVTFVPQNQT IESPDNALQFRLYGKDYNVYTHSFLAYGKDQ

- 103 046596

ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPATK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWE HIHFIG KIQGSDAGWTLGYMLNLTNM SEQ ID NO: 112 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGTGCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAACCCGGTGGTT CAGCATCGTGCCCTACGAGACAAA CAATCAGGAAACCTTCG GAGCCCTGGACCTGGGCGGAGCCTCTACCCAAGTGACCTTC GTGCCCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCT GCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTACACCC ACAGCTTTCTGGCCTACGGAAAGGACCAGGCCCTGTGGCAG AAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGATCCT GCGGGACCCTTGCTTCC ACCCCGGCTACAAGAAAGTCGTGA ACGTGTCCGACCTGTACAAGACCCCCGCCACCAAGAGATTC GAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATC GGCAACTACCAGCAGTGCCACCAGAGCATCCTGGAACTGTT CAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGG CATCTTCCTGCCACCTCTGCAGGGGGACTTCGGCGCTTTCAG CTACTTCGTGATGAAGTTCCTGAACCTGACCAGCGA GAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGAAG TTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTACGCT GGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCAGCGG TACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTTCAC CGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGATTC AG GGCAGCGACGCCGGCTGGACACTGGGCTACATGCTGAAT

- 104 046596

CTGACCAACATG CD39(aa46 461)_delt a-cys4 SEQ ID NO: 113 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARirrGQEE G A YGWITIN YLLGKFS QKTRWFSIVP YETNNQETFG ALDLGG A STQVTFVPQN QTIESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYAPYSQAAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKE KYLSEYCFSGTYILSLLLQGYHFTADSWE HIHFIGKIQGSDAGWTLGYMLNLTNM SEQ ID NO: 114 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGTGCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAACCCGGTGGTT CAGCATCGTGCCCTACGAGACAAA CAATCAGGAAACCTTCG GAGCCCTGGACCTGGGCGGAGCCTCTACCCAAGTGACCTTC GTGCCCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCT GCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTACACCC ACAGCTTTCTGTGCTACGGAAAGGACCAGGCCCTGTGGCAG AAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGATCCT GCGGGACCCTTGCTTCC ACCCCGGCTACAAGAAAGTCGTGA ACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGATTC GAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATC

- 105 046596

GGCAACTACCAGCAGTGCCACCAGAGCATCCTGGAACTGTT CAACACCAGCTACGCCCCCTACAGCCAGGCCGCCTTCAACG GCATCTTCCTGCCACCTCTGCAGGGGGACTTCGGCGCTTTCA GCGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAGCG AGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGAA GTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACC TCCTACG CTGGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCAGC GGTACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTTC ACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGAT TCAGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCTGA ATCTGACCAACATG CD39(aa46 461)_delt a-cys5 SEQ ID NO: 115 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARirrGQEE GAYGWITINYLLGKFSQKTRWFSIVPYETNNQETFGALDLGGA STQVTFVPQNQT IESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFAA QPWEEIKTSYAGVKEKY LSEYAFSGTYILSLLLQGYHFTADSWE HIHFIGKIQGSDAGWTLGYMLNLTNM SEQ ID NO: 116 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGTGCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC

- 106 046596

AACTACCTGCTGGGCAAGTTCAGCCAGAAAACCCGGTGGTT CAGCATCGTGCCCTACGAGACAAACAATCAGGAAACCTTCG GAGCCCTGGACCTGGGCGGAGCCTCTACCCAAGTGACCTTC GTGCCCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCT GCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTACACCC ACAGCTTTCTGTGCTACGGAAAGGACCAGGCCCTG TGGCAG AAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGATCCT GCGGGACCCTTGCTTCCACCCCGGCTACAAGAAAGTCGTGA ACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGATTC GAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATC GGCAACTACCAGCAGTGCCACCAGAGCATCCTGGAACTGTT CAACACCAGCTACTGCCCCTACAG CCAGTGCGCCTTCAACGG CATCTTCCTGCCACCTCTGCAGGGGGACTTCGGCGCTTTCAG CGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAGCGA GAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGAAG TTCGCCGCCCAGCCCTGGGAGGAAATCAAGACCTCTACGCT GGCGTGAAAGAGAAGTACCTGAGCGAGTACGCCTTCAGCGG TACCTACATCCTGAGCC TGCTGCTGCAGGGCTACCACTTCAC CGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGATTC AGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCTGAAT CTGACCAACATG CD39(aa46 461)_dMIL (193- 204)_delt a-cysl SEQ ID NO: 117 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEEARVK GPGISKFVQKVNEIGIYLTDAMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARIITGQEE GAYGWITINYLLGKFSQKNQETFGALDLGGASTQVTFVPQNQT IESPDNALQFRLYGK DYNVYTHSFLCYGKDQALWQKLAKDIQ VASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEMTLPFQQFE IQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPLQGDFGAF SAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWEEIKTSYA

- 107 046596

GVKEKYLSEYCFSGTYILSLLLQGYHFTADSWEHIHFIGKIQGSD AGWTLGYMLNLTNM SEQ ID NO: 118 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGGCCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACGCCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAAATCAGGAAAC CTTCGGAGCCCTGGACCTGGGC AGCCTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCCCTGTG GCAGAAGCTGGCCAAGCATCCAGGTGGCCAGCAACGAGA TCCTGCGGGACCCTTGCTTCCACCCCGGCTACAAGAAAGTCG TGAACGTGTCCGACCT GTACAAGACCCCCTGCACCAAGAGA TTCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGC ATCGGCAACTACCAGCAGTGCCACCAGAGCATCCTGGAACT GTTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAA CGGCATCTTCCTGCCACCTCTGCAGGGGGACTTCGGCGCTTT CAGCGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAG CGAGAAGG TGTCCCAGGAAAAAGTGACAGAGATGATGAAG AAGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTA CGCTGGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCA GCGGTACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACT TCACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAG ATTCAGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCT CCAACATG CD39(aa46 461)_dMIL

- 108 046596

(193204)_delt a-cys2 SEQ ID NO: 119 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARirrGQEE GAYGWITINYLLGKFSQKNQETFGALDLGGASTQVTFVPQNQT IESPDNALQFRLY GKDYNVYTHSFLCYGKDQALWQKLAKDIQ VASNEILRDPAFHPGYKKVVNVSDLYKTPCTKRFEMTLPFQQF EIQGIGNYQQAHQSILELFNTSYCPYSQCAFNGIFLPPLQGDFGA FSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWEEIKTSYA GVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHIHFIGKIQGSD AGWTLGYMLNLTNM SEQ ID NO: 120 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGTGCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAAATCAGGAAAC CTTCGGAGCCCTGGACCTGGGC AGCCTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCCCTGTG GCAGAAGCTGGCCAAGCATCCAGGTGGCCAGCAACGAGA TCCTGCGGGACCCTGCCTTCCACCCCGGCTACAAGAAAGTCG TGAACGTGTCCGACCT GTACAAGACCCCCTGCACCAAGAGA TTCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGC ATCGGCAACTACCAGCAGGCCCACCAGAGCATCCTGGAACT GTTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAA CGGCATCTTCCTGCCACCTCTGCAGGGGGACTTCGGCGCTTT

- 109 046596

CAGCGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAG CGAGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAG AAGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTA CGCTGGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCA GCGGTACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACT TCACCGCCGATAGCTGGGAGCACATCCACTTCATCG GCAAG ATTCAGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCT GAATCTGACCAACATG CD39(aa46 461)_dMIL (193204)_delt a-cys3 SEQ ID NO: 121 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARirrGQEE GAYGWITINYLLGKFSQKNQETFGALDLGGASTQVTFVPQNQT IESPDNALQFRLY GKDYNVYTHSFLAYGKDQALWQKLAKDIQ VASNEILRDPCFHPGYKKVVNVSDLYKTPATKRFEMTLPFQQF EIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPLQGDFGA FSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWEEIKTSYA GVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHIHFIGKIQGSD AGWTLGYMLNLTNM SEQ ID NO: 122 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGTGCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAAATCAGGAAAC

- 110 046596

CTTCGGAGCCCTGGACCTGGGCGGAGCCTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCAGCTTTCTGGCCTACGGAAAGGACCAGGCCCTGTG GCAGAAGCTGGCCAAGGACATCCAGGTGGCCAAGCAACGAGA TCCTGCGGGACCCTTGCTTCCACCCCGGCTACA AGAAAGTCG TGAACGTGTCCGACCTGTACAAGACCCCCGCCACCAAGAGA TTCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGC ATCGGCAACTACCAGCAGTGCCACCAGAGCATCCTGGAACT GTTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAA CGGCATCTTCCTGCCACCTGCAGGGGGACTTCGGCGCTTT CAGCGCCTTCTACTTCGTGATGAAG TTCCTGAACCTGACCAG CGAGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAG AAGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTA CGCTGGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCA GCGGTACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACT TCACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAG ATTCAGGGCAGCGACGCCGGCT GGACACTGGGCTACATGCT GAATCTGACCAACATG CD39(aa46 461)_dMIL (193- 204)_delt a-cys4 SEQ ID NO: 123 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARirrGQEE GAYGWITINYLLGKFSQKNQETFGALDLGGASTQVTFVPQNQT IESPDNALQFRLY GKDYNVYTHSFLCYGKDQALWQKLAKDIQ VASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEMTLPFQQFE IQGIGNYQQCHQSILELFNTSYAPYSQAAFNGIFLPPLQGDFGAF SAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWEEIKTSYA GVKEKYLSEYCFSGTYILSL LLQGYHFTADSWEHIHFIGKIQGSD AGWTLGYMLNLTNM

- 111 046596

SEQ ID NO: 124 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGTGCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAAATCAGGAAAC CTTCGGAGCCCTGGACCTGGGC AGCCTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCCCTGTG GCAGAAGCTGGCCAAGCATCCAGGTGGCCAGCAACGAGA TCCTGCGGGACCCTTGCTTCCACCCCGGCTACAAGAAAGTCG TGAACGTGTCCGACCT GTACAAGACCCCCTGCACCAAGAGA TTCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGC ATCGGCAACTACCAGCAGTGCCACCAGAGCATCCTGGAACT GTTCAACACCAGCTACGCCCCCTACAGCCAGGCCGCCTTCAA CGGCATCTTCCTGCCACCTCTGCAGGGGGACTTCGGCGCTTT CAGCGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAG CGAGAAGG TGTCCCAGGAAAAAGTGACAGAGATGATGAAG AAGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTA CGCTGGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCA GCGGTACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACT TCACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAG ATTCAGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCT CCAACATG CD39(aa46 461)_dMIL (193- 204)_delt

- 112 046596

a-cys5 SEQ ID NO: 125 Amino acids lots NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELADRVLDVVERSLSNYPFDFQGARirrGQEE GAYGWITINYLLGKFSQKNQETFGALDLGGASTQVTFVPQNQT IESPDNALQFRLY GKDYNVYTHSFLCYGKDQALWQKLAKDIQ VASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEMTLPFQQFE IQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPLQGDFGAF SAFYFVMKFLNLTSEKVSQEKVTEMMKKFAAQPWEEIKTSYA GVKEKYLSEYAFSGTYILSL LLQGYHFTADSWEHIHFIGKIQGS DAGWTLGYMLNLTNM SEQ ID NO: 126 DNA AACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCA CACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAA ACGATACCGGTGTCGTGCACCAGGTGGAAGAGTGCAGAGTG AAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGA GATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGAG AAGTGATCCCCAGAAGCCAGCACCAGGAAACC CCCGTGTAC CTGGGAGCCACAGCCGGCATGAGACTGCTGCGGATGGAAAG CGAGGAACTGGCCGACAGAGTGCTGGACGTGGTGGAAAGAA GCCTGAGCAACTACCCATTCGATTTTCAAGGGGCCAGAATCA TCACCGGCCAGGAAGAGGGCGCTTACGGCTGGATCACCATC AACTACCTGCTGGGCAAGTTCAGCCAGAAAAATCAGGAAAC CTTCGGAGCCCTGGACCTGGGC AGCCTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCCCTGTG GCAGAAGCTGGCCAAGCATCCAGGTGGCCAGCAACGAGA TCCTGCGGGACCCTTGCTTCCACCCCGGCTACAAGAAAGTCG TGAACGTGTCCGACCT GTACAAGACCCCCTGCACCAAGAGA TTCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGC ATCGGCAACTACCAGCAGTGCCACCAGAGCATCCTGGAACT GTTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAA CGGCATCTTCCTGCCACCTCTGCAGGGGGACTTCGGCGCTTT CAGCGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAG CGAGAAGG TGTCCCAGGAAAAAGTGACAGAGATGATGAAG

- 113 046596

AAGTTCGCCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTA CGCTGGCGTGAAAGAGAAGTACCTGAGCGAGTACGCCTTCA GCGGTACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACT TCACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAG ATTCAGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCT GAATCTGACCAACATG CD39(aa38 476)_delt a-337-344 SEQ ID NO: 127 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKTRWFSIVPYETNNQETFGA LDLGGASTQVTFVPQN QTIESPDNALQFRLYGKDYNVYTHSFL CYGKDQALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDL YKTPCTKRFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSFNGIF LPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQ PWEEIKTSYAGVKEKYLSEYCF SGTYILSLLLQGYHFTADSWEH IHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 128 DNA ACACAGAACAAAGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGATACCGGTGTCGTG CACCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGAAGTGATCCCC AGAAGC CAGCACCAGGAAACCCCCGTGTACCTGGGAGCCACAGCCGG CATGAGACTGCTGCGGATGGAAAGCGAGGAACTGGCCGACA GAGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGGGCCAGAATCACCGGCCAGGAAGA GGGCGCTTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAAACCCGGTGGTTCAGCATCG TGCCCTAC GAGACAAACAATCAGGAAACCTTCGGAGCCCTGGACCTGGG CGGAGCCTCTACCCAAGTGACCTTCGTGCCCCAGAATCAGAC CATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCTGTACG

- 114 046596

GCAAGGACTACAATGTGTACACCCACAGCTTTCTGTGCTACG GAAAGGACCAGGCCCTGTGGCAGAAGCTGGCCAAGGACATC CAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGCTTCCA CCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTGTACA AGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCCCTTCC AGCAGTTCGAGATCCAGGGCATCGGCAACT ACCAGCAGTGC CACCAGAGCATCCTGGAACTGTTCAACACCAGCTTCAACGG CATCTTCCTGCCACCTCTGCAGGGGGACTTCGGCGCTTTCAG CGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAGCGA GAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGAAG TTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCTACGCT GGCGTGAAAGAGAAGTACCTGAGCG AGTACTGCTTCAGCGG TACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTTCAC CGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGATTC AGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCTGAAT CTGACCAACATGATCCCCGCCGAGCAGCCCCTGAGCACACC TCTGTCTCACAGCACC CD39(aa38 476)_C338 A_C343A SEQ ID NO: 129 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKTRWFSIVPYETNNQETFGA LDLGGASTQVTFVPQN QTIESPDNALQFRLYGKDYNVYTHSFL CYGKDQALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDL YKTPCTKRFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYAPYS QAAFNGIFLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTE MMKKFCAQPWEEIKTSYAGVK EKYLSEYCFSGTYILSLLLQGY HFTADSWEHIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTP LSHST SEQ ID NO: 130 DNA ACACAGAACAAAGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGATACCGGTGTCGTG

- 115 046596

CACCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGAGAAGTGATCCCCAGAAGC CAGCACCAGGAAACCCCCGTGTACCTGGGAGCCACAGCCGG CATGAGACTGCTGCGGATGGAAAGCGAGGAACTGGCCGACA GAGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACT ACCCA TTCGATTTTCAAGGGGCCAGAATCACCGGCCAGGAAGA GGGCGCTTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAAACCCGGTGGTTCAGCATCGTGCCCTAC GAGACAAACAATCAGGAAACCTTCGGAGCCCTGGACCTGGG CGGAGCCTCTACCCAAGTGACCTTCGTGCCCCAGAATCAGAC CATCGAGAGCCCCGACAACGCCCTGCAGTTCC GGCTGTACG GCAAGGACTACAATGTGTACACCCACAGCTTTCTGTGCTACG GAAAGGACCAGGCCCTGTGGCAGAAGCTGGCCAAGGACATC CAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGCTTCCA CCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTGTACA AGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCCCTTCC AGCAGTTCGAGATCCAGGGCAT CGGCAACTACCAGCAGTGC CACCAGAGCATCCTGGAACTGTTCAACACCAGCTACGCCCCC TACAGCCAGGCCGCCTTCAACGGCATCTTCCTGCCACCTCTG CAGGGGGACTTCGGCGCTTTCAGCGCCTTCTACTTCGTGATG AAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAGGAAAA AGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCCCTGG AGGAAATCAAGACC TCCTACGCTGGCGTGAAAGAGAAGTAC CTGAGCGAGTACTGCTTCAGCGGTACCTACATCCTGAGCCTG CTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGGAGCA CATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCCGGCT GGACACTGGGCTACATGCTGAATCTGACCAACATGATCCCC GCCGAGCAGCCCCTGAGCACACCTCTGTCTCACAGCACC Expression mark aal- 16 SEQ ID Aminokis APTSSSTKKTQLTSSG

- 116 046596

NO: 131 lots SEQ ID NO: 132 DNA GCCCCCACCAGCAGCAGCACCAAGAAGACCCAGCTGACCAG CAGCGGC Expression mark aal- 15 SEQ ID NO: 133 Amino acids lots APTSSSTKKTQLTSS SEQ ID NO: 134 DNA GCCCCTACCAGCAGCAGCACCAAGAAAACCCAGCTGACCAG CAGC Expression mark aal- 6 SEQ ID NO: 135 Amino acids lots APTSSS SEQ ID NO: 136 DNA GCCCCTACCAGCAGCAGC Expression mark aal- 3 SEQ ID NO: 137 Amino acids lots APT SEQ ID NO: 138 DNA GCCCCTACC Expression mark aal-

- 117 046596

9 SEQ ID NO: 139 Amino acids lots APTSSSTKK SEQ ID NO: 140 DNA GCCCCTACCAGCAGCAGCACCAAGAAA Expression mark aal- 12 SEQ ID NO: 141 Amino acids lots APTSSSTKKTQL SEQ ID NO: 142 DNA GCCCCTACCAGCAGCAGCACCAAGAAAACCCAGCTG Expression mark aa4- 12 SEQ ID NO: 143 Amino acids lots SSSTKKTQL SEQ ID NO: 144 DNA AGCAGCAGCACCAAGAAAACCCAGCTG EP28_8M SEQ ID NO: 145 Amino acids lots TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQDEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQVT FVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGRDQALWQ KLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEM TLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFLPPL QGDFGAFSNFYYVMKFLNLTSEKVSQEKVTEMMKKFCAQPWE EIKTSYAGQERWLRDYCFSGTYILSL LLQGYHFTADSWEHIHFI

- 118 046596

GKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 146 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCACCGGCCAGGACGA GGGCGCCTACGGCTGGATCACCATCAACCTGCTGGGCA AGTTCAGCCAGAATCAGGAAACCTTC CGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGCCGGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGC TTCCACCCCGGCTACAAG GTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAACTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGGGATTTCGGCGCCTTCAGCAACTTCTACTACG TGATGA AGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCTTACGCCGGACAGGAACGGT GGCTGCGGGACTACTGTTTCAGCGGCACCTACATCCTGTCCC TGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGGAGC ACATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCCGGC TGGACACTGGGCTACATGCTGAATCTGACCAACATGATCCCC GCCGAGCAGCCCCTGAGCACACCTCTGTCTCACAGCACC CD39(aa38 476)_dMIL

- 119 046596

(193204)_SCAPPA SEQ ID NO: 147 Amino acids lots TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYAC EVTHQGLSSPVTKSFNRGEGGGGSTQNKALPENVKYGIVLDAG SSHTSLYIYKWPAEKENDTGVVHQVEECRVKGPGISKFVQKVN EIGIYLTDCMERARE VIPRSQHQETPVYLGATAGMRLLRMESEE LADRVLDVVERSLSNYPFDFQGARIITGQEEGAYGWITINYLLG KFSQKNQETFGALDLGGASTQVTFVPQNQTIESPDNALQFRLY GKDYNVYTHSFLCYGKDQALWQKLAKDIQVASNEILRDPCFHP GYKKVVNVSDLYKTPCTKRFEMTLPFQQFEIQ GIGNYQQCHQSI LELFNTSYCPYSQCAFNGIFLPPLQGDFGAFSAFYFVMKFLNLTS EKVSQEKVTEMMKKFCAQPWEEIKTSYAGVKEKYLSEYCFSG TYILSLLLQGYHFTADSWEHIHFIGKIQGSDAGWTLGYMLNLTN MIPAEQPLSTPLSHST SEQ ID NO: 148 DNA ACGGTGGCCGCTCCCAGCGTGTTCATCTTCCCCCCCAGCGAC GAGCAGCTGAAGAGCGGCACCGCCAGCGTGGTGTGCCTGCT GAACAACTTCTACCCCCGGGAGGCCAAGGTGCAGTGGAAGG TGGACAACGCCCTGCAGAGCGGCAACAGCCAGGAAAGCGTC ACCGAGCAGGACAGCAAGGACTCCACCTACAGCCTGAGCAG CACCCTGACCCTGAGCAAGGCCGACTACGAGAAG CACAAGG TGTACGCTGCGAGGTGACCCACCAGGGCCTGTCCAGCCCC GTGACCAAGAGCTTCAACCGGGGCGAGGGAGGCGGAGGATC TACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCA TCGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGG CATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCCCCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTAC CTGCTGGGCA

- 120 046596

AGTTCAGCCAGAAGAATCAGGAAACCTTTCGGCGCCCTGGAC CTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAAT CAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCT GTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCTGTG CTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGG ACATCCAGGTGGCCAGCAACGAGATCC TGCGGGACCCTTGC TTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTG TACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCC CTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGC AGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCTACT GCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCAC CTCTGCAGGGAT TTCGGCGCCTTCAGCGCCTTCTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCC CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGG CATCCACTTCATCGCAAGATTCAGGGCAGCGACGCC GGCTGGACACTGGGCTACATGCTGAATCTGACCAACATGAT CCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCA CC CD39(aa38 476)_dMIL (193204)_UBI SEQ ID NO: 149 Amino acids lots MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFA GKQLEDGRTLSDYNIQKESTLHLVLRLRGGGGGGSTQNKALPE NVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVK GPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGAT AGMRLLRMESEELA DRVLD VVERS LSNYPFDFQGARirTGQEE GAYGWITINYLLGKFSQKNQETFGALDLGGASTQVTFVPQNQT IESPDNALQFRLYGKDYNVYTHSFLCYGKDQALWQKLAKDIQ VASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRFEMTLPFQQFE IQGIGNYQQCHQSILELFNTSYCPYSQCA FNGIFLPPLQGDFGAF

- 121 046596

SAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQPWEEIKTSYA GVKEKYLSEYCFSGTYILSLLLQGYHFTADSWEHIHFIGKIQGSD AGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 150 DNA ATGCAAATCTTCGTGAAGACCCTGACTGGTAAGACCATCACC CTCGAGGTGGAGCCCAGTGACACCATCGAGAATGTCAAGGC AAAGATCCAAGATAAGGAAGGCATCCCCTCCTGATCAGCAGA GGTTGATCTTTGCTGGGAAACAGCTGGAAGATGGACGCACC CTGTCTGACTACAACATCCAGAAAGAGTCCACTCTGCACTTG GTCCTGCGCTTGAGGGGGGGTGGAGGCGGAGGATCTA CCCA GAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCATCGTGC TGGATGCCGGCAGCAGCCACACCAGCCTGTACATCTACAAG TGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTGCATCA GGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAGCAAGT TCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGACCGAC TGCATGGAACGGGCCAGGGAAGT GATCCCCAGAAGCCAGCA CCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGGCATGA GACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACCGGGTG CTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCATTCGA TTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGAAGGCG CCTACGGCTGGATCACCATCAACTACCTGCTGGGCAAGTTCA GCCAGAAATCAGGAAACCTTC GGCGCCCTGGACCTGGGC GGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAATCAGACC ATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCTGTACGG CAAGGACTACAATGTGTACACCCACAGCTTTCTGTGCTACGG AAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGGACATCC AGGTGGCCAGCAACGAGATCCTGCGGGACCCTTGCTTCCACAAA CCCGGCTACAAGAAA GTCGTGAACGTGTCCGACCTGTACAA GACCCCCTGCACCAAGAGATTCGAGATGACCCTGCCCTTCCA GCAGTTCGAGATCCAGGGCATCGGCAATTACCAGCAGTGCC ACCAGAGCATCCTGGAACTGTTCAACACCAGCTACTGCCCCT ACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCACCTCTGC AGGGGGATTTCGGCGCCTTCAGCGCCTTCTACTTCGTGATGA TCCTGAACCTGACCAGCGAGAAGGTGTCCCAGGAAAAA GTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCCCTGGGA GGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGAAGTACC

- 122 046596

TGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGAGCCTGC TGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGGAGCAC ATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCCGGCTG GACACTGGGCTACATGCTGAATCTGACCAACATGATCCCCGC CGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCACC CD39(aa38 476)_dMIL (193- 204)_HSAI HSAdomain!G4SCD39dMIL SEQ ID NO: 151 Amino acids lots DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLV NEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGE MADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFH DNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQA ADKAACLPKLDELRGGGGSTQNKALPENVKY GIVLDAGSSHT SLYIYKWPAEKENDTGVVHQVEECRVKGPGISKFVQKVNEIGI YLTDCMERAREVIPRSQHQETPVYLGATAGMRLLRMESEELAD RVLDVVERSLSNYPFDFQGARIITGQEEGAYGWITINYLLGKFS QKNQETFGALDLGGASTQVTFVPQNQTIESPDNALQFRLYGKD LSLLLQGYHFTADSW EHIHFIGKIQGSDAGWTLGYMLNLTNMI PAEQPLSTPLSHST SEQ ID NO: 152 DNA GACGCCCACAAGAGCGAGGTGGCCCACCGGTTCAAGGACCT GGGCGAGGAAAACTTCAAGGCCCTGGTGCTGATCGCCTTCG CCCAGTACCTGCAGCAGAGCCCCTTCGAAGATCACGTAAAG TTAGTCAACGAGGTTACGGAATTCGCAAAGACATGCGTTGCT GACGAATCCGCTGAGAATTGTGACAAGAGTTTGCACACTTTA TTCGGAGATAAGTTGTGTACTG TAGCTACTTTGAGAGAGACT TACGGTGAAATGGCTGACTGCTGTGCAAAACAGGAACCAGA ACGTAACGAATGTTTCCTTCAGCATAAGGATGATAACCCTAA CCTTCCAAGCTTGTTAGGCCAGAAGTCGACGTGATGTGCAC CGCCTTCCATGATAATGAAGAGACTTTTCTTAAAAAGTACCT

- 123 046596

ATACGAGATTGCAAGGCGTCATCCATATTTTTACGCCCCAGA GCTGTTGTTTTTCGCAAAGAGATACAAAGCTGCATTTACTGA GTGTTGCCAAGCTGCCGACAAGGCCGCTTGTTTGCTACCAAA GTTGGACGAATTGAGAGGAGGCGGAGGATCTACCCAGAACA AGGCCCTGCCCGAGAACGTGAAGTACGGCATCGTGCTGGAT GCCGGCAGCAGCCACCAGCCTGTACATC TACAAGTGGCC TGCCGAGAAAGAAAACGACACCGGCGTGGTGCATCAGGTGG AAGAGTGCAGAGTGAAGGGCCCTGGCATCAGCAAGTTCGTG CAGAAAGTGAACGAGATCGGCATCTACCTGACCGACTGCAT GGAACGGGCCAGGGAAGTGATCCCCAGAAGCCAGCACCAG GAAACCCCCGTGTATCTGGGAGCCACCGCCGGCATGAGACT GCTGAGAATGGAAAGCGAGGAACT CCGACCGGGTGCTGG ACGTGGTGGAAAGAAGCCTGAGCAACTACCCATTCGATTTTC AAGGCGCCAGAATCATCACCGGCCAGGAAAGGCGCCTAC GGCTGGATCACCATCAACTACCTGCTGGGCAAGTTCAGCCA GAAGAATCAGGAAACCTTCGGCGCCCTGGACCTGGGCGGAG CTTCTACCCAAGTGACCTTCGTGCCCCAGAATCAGACCATCG AGAGCCCCGACAACGCCCT GCAGTTCCGGCTGTACGGCAAG GACTACAATGTGTACACCCACAGCTTTCTGTGCTACGGAAAG GACCAGGCTCTGTGGCAGAAGCTGGCCAAGGACATCCAGGT GGCCAGCAACGAGATCCTGCGGGACCCTTGCTTCCACCCCG GCTACAAGAAAGTCGTGAACGTGTCCGACCTGTACAAGACC CCCTGCACCAAGAGATTCGAGATGACCCTGCCCTTCCAGCAG TTCGA GATCCAGGGCATCGGCAATTACCAGCAGTGCCACCA GAGCATCCTGGAACTGTTCAACACCAGCTACTGCCCCTACAG CCAGTGCGCCTTCAACGGCATCTTCCTGCCACCTCTGCAGGG GGATTTCGGCGCCTTCAGCGCCTTCTACTTCGTGATGAAGTT CCTGAACCTGACCAGCGAGAAGGTGTCCCAGGAAAAAGTGA CAGAGATGATGAAGAAGTTCTGCGCCCAGCCCTGGGAGGAA ATCAAGACCTCCTACGCTGGCGTGAAAGAGAAGTACCTGAG CGAGTACTGCTTCAGCGGCACCTACATCCTGAGCCTGCTGCT GCAGGGCTACCACTTCACCGCCGATAGCTGGGAGCACATCC ACTTCATCGGCAAGATTCAGGGCAGCGACGCCGGCTGGACA CTGGGCTACATGCTGAATCTGACCAACATGATCCCCGCCGAG CAGCCCCTGAGCACACCTCTGAGCCACACC

- 124 046596

CD39(aa38 476)_dMIL (193- 204)_HSAI I SEQ ID NO: 153 Amino acids lots DEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEF AEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSI SSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDV CKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTL EKCCAAADPHECYAKVFDEFKPGGGGST QNKALPENVKYGIV LDAGSSHTSLYIYKWPAEKENDTGVVHQVEECRVKGPGISKFV QKVNEIGIYLTDCMERAREVIPRSQHQETPVYLGATAGMRLLR MESEELADRVLDVVERSLSNYPFDFQGARIITGQEEGAYGWITI NYLLGKFSQKNQETFGALDLGGASTQVTFVPQNQTIESPDNAL KDYNVYTHSFLCYGKDQALWQKLAKDIQVASNEILR DPCFHPGYKKVVNVSDLYKTPCTKRFEMTLPFQQFEIQGIGNY QQCHQSILELFNTSYCPYSQCAFNGIFLPPLQGDFGAFSAFYFV MKFLNLTSEKVSQEKVTEMMKKFCAQPWEEIKTSYAGVKEKY LSEYCFSGTYILSL LLQGYHFTADSWEHIHFIGKIQGSDAGWTL GYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 154 DNA GACGAGGGTAAGGCATCATCTGCCAAGCAGAGATTAAAATG TGCATCTTTGCAAAAATTTGGAGAGAGAGCTTTTAAGGCATG GGCTGTTGCCCGACTAAGCCAAAGATTCCCAAAAGCCGAAT TTGCTGAAGTATCCAAGCTGGTGACTGATTTGACTAAAGTAC ATACAGAATGTTGCCATGGCGACCTTTTAGAATGTGCTGATG ACAGAGCAGATTTGGCTAAGTATATCTGCGAAAATCA AGAT TCAATCAGCTCTAAGCTGAAGGAATGTTGCGAGAAACCACT GTTAGAAAAATCGCATTGTATTGCTGAAGTTGAAAATGATG AGATGCCTGCTGACTTGCCTTCTCTTGCCGCTGATTTTGTTGA GTCGAAGGATGTCTGTAAGAATTATGCTGAAGCTAAAGACG TTTTCCTGGGTATGTTCTTATATGAGTACGCAAGACGTCACC CAGATTACTCTGTGGTTCTGCTACTGAGA TTGGCTAAAACAT ACGAGACAACGCTGGAGAAGTGCTGTGCTGCCGCTGACCCT CATGAGTGCTATGCAAAGGTTTTTGATGAATTCAAACCAGGA

- 125 046596

GGCGGAGGATCTACCCAGAACAAGGCCCTGCCCGAGAACGT GAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCCACACCA GCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAAAACGAC ACCGGCGTGGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGG CCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACGAGATCG GCATCTACCTGACCGACTGCATGGAACGGGCCA GGGAAGTG ATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGTATCTGGG AGCCACCGCCGGCATGAGACTGCTGAGAATGGAAAGCGAGG AACTGGCCGACCGGGTGCTGGACGTGGTGGAAAGAAGCCTG AGCAACTACCCATTCGATTTTCAAGGCGCCAGAATCATCACC GGCCAGGAAGAAGGCGCCTACGGCTGGATCACCATCAACTA CCTGCTGGGCAAGTTCAGCCAGAAGAAT CAGGAAACCTTCG GCGCCCTGGACCTGGGCGGAGCTTCTACCCAAGTGACCTTCG TGCCCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCTG CAGTTCCGGCTGTACGGCAAGGACTACAATGTGTACACCCA CAGCTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGGCAGA AGCTGCCAAGGACATCCAGGTGGCCAGCAACGATCCTG CGGGACCCTTGCTTCCACCCCG GCTACAAGAAAGTCGTGAA CGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGATTCG AGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCG GCAATTACCAGCAGTGCCACCAGAGCATCCTGGAACTGTTC AACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGGC ATCTTCCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTCAGC GTGATGAAGTTCCTGAACCTGACCAGCGAG AAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGAAGTT CTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTACGCTG GCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCAGCGGC ACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTTCACC GCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGATTCA GGGCAGCGA CGCCGGCTGGACACTGGGCTACATGCTGAATC TGACCAACATGATCCCCGCCGAGCAGCCCCTGAGCACACCT CTGAGCCACAGCACC EP14 with MIL SEQ ID Aminokis TQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGVVHQ

- 126 046596

NO: 155 lots VEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQHQET PVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQGA RIITGQEEGAYGWITINYLLGKFSQKTRWFSIVPYETNNQETFGA LDLGGASTQVTFVPQNQTIESPDNALQFRLYGKDYNVYTHSFL CYGKDQALWQKLA KDIQVASNEILRDPCFHPGYKKVVNVSDL YKTPCTKRFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYS QCAFNGIFLPPLQGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEM MKKFCAQPWEEIKTSYAGVKEKYLSEYCFSGTYILSLLLQGYH FTADSWEHIHFIGKIQGSDAGW TLGYMLNLTNMIPAEQPLSTPL SHST SEQ ID NO: 156 DNA ACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACGGCAT CGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTACATCT ACAAGTGGCCTGCCGAGAAAGAAAACGACACCGGCGTGGTG CATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCATCAG CAAGTTCGTGCAGAAAGTGAACGAGATCGGCATCTACCTGA CCGACTGCATGGAACGGGCCAGGGAAGTGATCC CCAGAAGC CAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCGCCGG CATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCCGACC GGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTACCCA TTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGAAGA AGGCGCCTACGGCTGGATCACCATCAACTACCTGCTGGGCA AGTTCAGCCAGAAGACCAGATGGTTCAGCAT CGTGCCCTAC GAGACAAACAATCAGGAAACCTTCGGCGCCCTGGACCTGGG CGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAGAATCAGAC CATCGAGAGCCCCGACAACGCCCTGCAGTTCCGGCTGTACG GCAAGGACTACAATGTGTACACCCAGCTTTCTGTGCTACG GAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCAAGGACATC CAGGTGGCCAGCAACGAGATCCTGC GGGACCCTTGCTTCCA CCCCGGCTACAAGAAAGTCGTGAACGTGTCCGACCTGTACA AGACCCCCTGCACCAAGAGATTCGAGATGACCCTGCCCTTCC AGCAGTTCGAGATCCAGGGCATCGGCAATTACCAGCAGTGC CACCAGAGCATCCTGGAACTGTTCAACACCAGCTACTGCCCC TACAGCCAGTGCGCCTTCAACGGCATCTTCCTGCCACCTCTG CAGGGGGATTTCGGCGC CTTCAGCGCCTTCTACTCCGTGATG AAGTTCCTGAACCTGACCAGCGAGAAGGTGTCCCAGGAAAA

- 127 046596

AGTGACAGAGATGATGAAGAAGTTCTGCGCCCAGCCCTGGG AGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGAAGTAC CTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGAGCCTG CTGCTGCAGGGCTACCACTTCACCGCCGATAGCTGGGAGCA CATCCACTTCATCGGCAAGATTCAGGGCAGCGACGCCGGCT GGACACTGGGCTACATGCTGAATCTGACCAACAT GATCCCC GCCGAGCAGCCCCTGAGCACACCTCTGAGCCACAGCACC SEQ ID NO: 157 Direct primer TCGCGATCCTGGAAGGCGTGCACTGCGCCCCTACCAGCAGC AGCACCAAGAAAACCCAGCTGACCAGCAGCACCCAGAACAA GGCCCTGC SEQ ID NO: 158 Reverse primer TAGAAGGCACAGTCGAGG SEQ ID NO: 159 Direct primer CTGGTCGCGATCCTGGAAGGCGTGCACTGCGCCCCTACCAGC AGCAGCACCCAGAACAAGGCCCTG SEQ ID NO: 160 Direct primer CTGGTCGCGATCCTGGAAGGCGTGCACTGCGCCCCTACCAGC AGCAGCACCCAGAACAAGGCCCTG SEQ ID NO: 161 Direct primer CTGGTCGCGATCCTGGAAGGCGTGCACTGCGCCCCTACCACC CAGACAAGGCCCTG SEQ ID NO: 162 Direct primer CTGGTCGCGATCCTGGAAGGCGTGCACTGCGCCCCTACCAGC AGCAGCACCAAGAAAACCCAGAACAAGGCCCTG SEQ ID NO: 163 Direct primer CTGGTCGCGATCCTGGAAGGCGTGCACTGCGCCCCTACCAGC AGCAGCACCAAGAAAACCCAGCTGACCCAGAACAAGGCCCT G SEQ ID NO: 164 Direct primer CTGGTCGCGATCCTGGAAGGCGTGCACTGCAGCAGCAGCAC CAAGAAAACCCAGCTGACCCAGAACAAGGCCCTG SEQ ID NO: 165 Primer P270 CATACGATTTAGGTGA SEQ ID NO: 166 Primer P271 TAGAAGGCACAGTCGAGG SEQ ID NO: 167 Ubiquity new label MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFA GKQLEDGRTLSDYNIQKESTLHLVLRLRGG SEQ ID NO: 168 Scappa's Mark TVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYAC

- 128 046596

EVTHQGLSSPVTKSFNRGE SEQ ID NO: 169 Label representing domain I HSA DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQSPFEDHVKLV NEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGE MADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFH DNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQA ADKAACLLPKLDELR SEQ ID NO: 170 Label representing domain II HSA DEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEF AEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSI SSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDV CKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTL EKCCAAADPHECYAKVFDEFKP SEQ ID NO: 171 Primer P928 CTGCCGAGAAAGAACAGGACACCGGCGTGG SEQ ID NO: 172 Primer P929 CCACGCCGGTGTCCTGTTCTTTCTCGGCAG SEQ ID NO: 173 Primer P930 CGTGCCCCAGAATCAGGCCATCGAGAGCC SEQ ID NO: 174 Primer P931 GGCTCTCGATGGCCTGATTCTGGGGCACG SEQ ID NO: 175 Primer P932 GGCTACAAGAAAGTCGTGCAGGTGTCCGACCTGTACAAGAC SEQ ID NO: 176 Primer P933 GTCTTGTACAGGTCGGACACCTGCACGACTTTCTTGTAGCC SEQ ID NO: 177 Primer P934 GCATCCTGGAACTGTTCCAGACCAGCTACTGCCCC SEQ ID NO: 178 Primer P935 GGGGCAGTAGCTGGTCTGGAACAGTTCCAGGATGC SEQ ID NO: 179 Primer P936 CCGTGATGAAGTTCCTGCAGCTGACCAGCGAGAAG SEQ ID NO: 180 Primer P937 CTTCTCGCTGGTCAGCTGCAGGAACTTCATCACGG SEQ ID Primer CACTGGGCTACATGCTGCAGCTGACCAACATGATCC

- 129 046596

NO: 181 P938 SEQ ID NO: 182 Primer P939 GGATCATGTTGGTCAGCTGCAGCATGTAGCCCAGTG SEQ ID NO: 183 Primer P878 CTACATCCTGAGCCTGCTGCAGCAGGGCTACCACTTCAC SEQ ID NO: 184 Primer P879 GTGAAGTGGTAGCCCTGCTGCAGCAGGCTCAGGATGTAG SEQ ID NO: 185 Primer Р88О GAGAAGTACCTGAGCGAGTTTTGCTTCAGCGGCACCTACATC C SEQ ID NO: 186 Primer P881 GGATGTAGGTGCCGCTGAAGCAAAACTCGCTCAGGTACTTCT C SEQ ID NO: 187 Primer P882 GTTCGAGATCCAGGGCACCGGCAATTACCAGCAGTG SEQ ID NO: 188 Primer P883 CACTGCTGGTAATTGCCGGTGCCCTGGATCTCGAAC SEQ ID NO: 189 Primer P884 CGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAG SEQ ID NO: 190 Primer P885 CTTGCCGATGAAGTGGATGTGCTCCCAGCTATCGGCG SEQ ID NO: 191 R113M, matrix GAGATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAT GGAAGTGATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGT ATCTGGGAGCCACCGCCGGCATGAGACTGCTGAGAATG SEQ ID NO: 192 R113M, straight GAGATCGGCATCTACCTGACCGACT SEQ ID NO: 193 R113M, reverse CATTCTCAGCAGTCTCAT SEQ ID NO: 194 F33OS, matrix CTTCAGCGCCTTCTACTcCGTGATGAAGTTCCTGAACCTGACC AGCGAGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGA AGAAGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGAC SEQ ID NO: 195 F33OS, straight CTTCAGCGCCTTCTACTCC SEQ ID NO: 196 F33OS, reverse GGTCTTGATTTCCTCCCAG SEQ ID Y377F, CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA

- 130 046596

NO: 197 matrix AGTACCTGAGCGAGTtCTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATA SEQ ID NO: 198 L389C, matrix CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCaGCAGGGGCTACCACTTCACCGCCGATA SEQ ID NO: 199 Y377F/L3 89Q, matrix CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTTCTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCaGCAGGGCTACCACTTCACCGCCGATA SEQ ID NO: 200 Direct primer CTGGGAGGAAATCAAGACC SEQ ID NO: 201 Reverse primer TATCGGCGGTGAAGTGGTA SEQ ID NO: 202 Primer for WT CTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAAAGAGA AGTACCTGAGCGAGTACTGCTTCAGCGGCACCTACATCCTGA GCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATA SEQ ID NO: 203 Direct for Mutl74 CACCGGCCAGGAAGCCGGCGCCTACG SEQ ID NO: 204 Back FOR Mutl74 CGTAGGCGCCGGCTTCCTGGCCGGTG SEQ ID NO: 205 Direct to Mut218 GGACCTGGGCGGAGCTGCTACCCAAGTGACCTTC SEQ ID NO: 206 Back FOR Mut218 GAAGGTCACTTGGGTAGCAGCTCCGCCCAGGTCC SEQ ID NO: 207 Direct for protein with MIL CTGGATCACCATCAACTACCTGCTGGGCAAGTTCAGCCAGA AGACCAGATGGTTCAGCATCGTGCCCTACGAGACAAACA SEQ ID NO: 208 Reverse for protein with MIL TCACTTGGGTAGAAGCTCCGCCCAGGTCCAGGGCGCCGAAG GTTTCCTGATTGTTTGTCTCGTAGGGCA EPlaal-3

- 131 046596

SEQ ID NO: 209 Amino acids lots APTTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGV VHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQH QETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQ GARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQ VTFVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQAL WQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRF EMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFL PPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQP WEEIKTSYAGVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHI HFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 210 DNA GCCCCTACCACCCAGAACAAGGCCCTGCCCGAGAACGTGAA GTACGGCATCGTGCTGGATGCCGGCAGCAGCCACACCAGCC TGTACATCTACAAGTGGCCTGCCGAGAAAGAAAACGACACC GGCGTGGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGGCCC TGGCATCAGCAAGTTCGTGCAGAAAGTGAACGAGATCGGCA TCTACCTGACCGACTGCATGGAACGGGCCATG GAAGTGATC CCCAGAAGCCAGCACCAGGAAACCCCCGTGTATCTGGGAGC CACCGCCGGCATGAGACTGCTGAGAATGGAAAGCGAGGAAC TGGCCGACCGGGTGCTGGACGTGGTGGAAAGAAGCCTGAGC AACTACCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGC CAGGAAGAAGGCGCCTACGGCTGGATCACCATCAACTACCT GCTGGGCAAGTTCAGCCAGAAGA ATCAGGAAACCTTTCGGCG CCCTGGACCTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGC CCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCTGCAG TTCCGGCTGTACGGCAAGGACTACAATGTGTACACCCACAG CTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGGCAGAAGCT GGCCAAGGACATCCAGGTGGCCAGCAACGATCCTGCGGG ACCCTTGCTTCCACCCC GGCTACAAGAAAGTCGTGAACGTGT CCGACCTGTACAAGACCCCCTGCACCAAGAGATTCGAGATG ACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAAT TACCAGCAGTGCCACCAGAGCATCCTGGAACTGTTCAACAC CAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGGCATCTT CCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTT CTACTTCG TGATGAAGTTCCTGAACCTGACCAGCGAGAAGGT GTCCCAGGAAAAAGTGACAGAGATGATGAAGAAGTTCTGCG

- 132 046596

CCCAGCCCTGGGAGGAAATCAAGACCTCCTACGCTGGCGTG AAAGAGAAGTACCTGAGCGAGTACTGCTTCAGCGGCACCTA CATCCTGAGCCTGCTGCTGCAGGGCTACCACTTCACCGCCGA TAGCTGGGAGCACATCCACTTCATCGGCAAGATTCAGGGCA GCGACGCCGGCTGGACACTGGGCTACATGCTGAATCTGACC AACATGATCCCCGCCGAGCAGCCCCTGAGCACACC TCTGAG CCACAGCACC EP1xEP17a al-3 SEQ ID NO: 211 Amino acids lots APTTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGV VHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQH QETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQ GARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQ VTFVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQAL WQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRF EMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFL PPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQP WEEIKTSYAGVKEKYLSEFCFSGTYIL SLLLQGYHFTADSWEHI HFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 212 DNA GCCCCTACCACCCAGAACAAGGCCCTGCCCGAGAACGTGAA GTACGGCATCGTGCTGGATGCCGGCAGCAGCCACACCAGCC TGTACATCTACAAGTGGCCTGCCGAGAAAGAAAACGACACC GGCGTGGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGGCCC TGGCATCAGCAAGTTCGTGCAGAAAGTGAACGAGATCGGCA TCTACCTGACCGACTGCATGGAACGGGCCATG GAAGTGATC CCCAGAAGCCAGCACCAGGAAACCCCCGTGTATCTGGGAGC CACCGCCGGCATGAGACTGCTGAGAATGGAAAGCGAGGAAC TGGCCGACCGGGTGCTGGACGTGGTGGAAAGAAGCCTGAGC AACTACCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGC CAGGAAGAAGGCGCCTACGGCTGGATCACCATCAACTACCT GCTGGGCAAGTTCAGCCAGAAGA ATCAGGAAACCTTTCGGCG CCCTGGACCTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGC CCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCTGCAG TTCCGGCTGTACGGCAAGGACTACAATGTGTACACCCACAG CTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGGCAGAAGCT

- 133 046596

GGCCAAGGACATCCAGGTGGCCAGCAACGAGATCCTGCGGG ACCCTTGCTTCCACCCCGGCTACAAGAAAGTCGTGAACGTGT CCGACCTGTACAAGACCCCCTGCACCAAGAGATTCGAGATG ACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAAT TACCAGCAGTGCCACCAGAGCATCCTGGAACTGTTCAACAC CAGCTACTGCCCCTACAGCCAGTGCGCCTTCAAC GGCATCTT CCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTT CTACTTCGTGATGAAGTTCCTGAACCTGACCAGCGAGAAGGT GTCCCAGGAAAAAGTGACAGAGATGATGAAGAAGTTCTGCG CCCAGCCCTGGGAGGAAATCAAGACCTCTACGCTGGCGTG AAAGAGAAGTACCTGAGCGAGTTTTGCTTCAGCGGCACCTA CATCCTGAGCCTGCTGCTGCAGC TACCACTTCACCGCCGA TAGCTGGGAGCACATCCACTTCATCGGCAAGATTCAGGGCA GCGACGCCGGCTGGACACTGGGCTACATGCTGAATCTGACC AACATGATCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAG CCACAGCACC EP1xEP17a al-6 SEQ ID NO: 213 Amino acids lots APTSSSTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDT GVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRS QHQETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPF DFQGARIITGQEEGAYGWrriNYLLGKFSQKNQETFGALDLGGA STQVTFVPQNQT IESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEKY LSEFCFSGTYILSLLLQGYHFTADSWE HIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 214 DNA GCCCCTACCAGCAGCAGCACCCAGAACAAGGCCCTGCCCGA GAACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCC ACACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAA AACGACACCGGCGTGGTGCATCAGGTGGAAGAGTGCAGAGT GAAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACG AGATCGGCATCTACCTGACCGACTGCATG GAACGGGCCATG GAAGTGATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGTA

- 134 046596

TCTGGGAGCCACCGCCGGCATGAGACTGCTGAGAATGGAAA GCGAGGAACTGGCCGACCGGGTGCTGGACGTGGTGGAAAGA AGCCTGAGCAACTACCCATTCGATTTTCAAGGCGCCAGAATC ATCACCGGCCAGGAAGAAGGCGCCTACGGCTGGATCACCAT CAACTACCTGCTGGGCAAGTTCAGCCAGAATCAGGAAA CCTTCGGCGCCCTGGACCTGGGCGGAGCTTCTACC CAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGG CAGAAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGAT CCTGCGGGACCCTTGCTTCCACCCCGGCTACAAGAAAGTCGT GAACGTGTCCGACCTGTACAAGACC CCCTGCACCAAGAGAT TCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCA TCGGCAATTACCAGCAGTGCCACCAGAGCATCCTGGAACTG TTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAAC GGCATCTTCCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTC AGCGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAGC GAGAAGGTGTCCCAG GAAAAAGTGACAGAGATGATGAAGA AGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTAC GCTGGCGTGAAAGAGAAGTACCTGAGCGAGTTCTGCTTCAG CGGCACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTT CACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGA TTCAGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCTG AATCTGACCAACATGATCCC CGCCGAGCAGCCCCTGAGCAC ACCTCTGAGCCACAGCACC ΕΡ1χΕΡ17_ K405Naal15 SEQ ID NO: 215 Amino acids lots APTSSSTKKTQLTSSTQNKALPENVKYGIVLDAGSSHTSLYIYK WPAEKENDTGVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCM ERAMEVIPRSQHQETPVYLGATAGMRLLRMESEELADRVLDV VERSLSNYPFDFQGARIITGQEEGAYGWITINYLLGKFSQKNQE TFGALDLGGASTQVTF VPQNQTIESPDNALQFRLYGKDYNVYT HSFLCYGKDQALWQKLAKDIQVASNEILRDPCFHPGYKKVVN VSDLYKTPCTKRFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSY

- 135 046596

CPYSQCAFNGIFLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEK VTEMMKKFCAQPWEEIKTSYAGVNEKYLSEFCFSGTYILSLLLQ GYHFTADSWEHIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPL STPLSHST SEQ ID NO: 216 DNA GCCCCTACCAGCAGCAGCACCAAGAAAACCCAGCTGACCAG CAGCACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACG GCATCGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTAC ATCTACAAGTGGCCTGCCGAAAGAAAACGACACCGGCGT GGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCA TCAGCAAGTTCGTGCAGAAAGTGAACGAGA TCGGCATCTAC CTGACCGACTGCATGGAACGGGCCATGGAAGTGATCCCCAG AAGCCAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCG CCGGCATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCC GACCGGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTA CCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGA AGAAGGCGCCTACGGCTGGATCACCATCA ACTACCTGCTGG GCAAGTTCAGCCAGAAGAATCAGGAAACCTTCGGCGCCCTG GACCTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAG AATCAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCG GCTGTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCT GTGCTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCA AGGACATCCAGGTGGCC AGCAACGAGATCCTGCGGGACCCT TGCTTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGAC CTGTACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCT GCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCA GCAGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCT ACTGCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGC CACCTCTGCA GGGGGATTTCGGCCTTCAGCGCCTTCTACT TCGTGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCC CAGGAAAAAGTGACAGAGATGATGAAGAAGTTCTGCGCCCA ACCCTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGAACG AGAAGTACCTGAGCGAGTTTTGCTTCAGCGGCACCTACATCC TGAGCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCT AGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGAC GCCGGCTGGACACTGGGCTACATGCTGAATCTGACCAACAT

- 136 046596

GATCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACA GCACC ΕΡ1χΕΡ17χ EP19aal-3 SEQ ID NO: 217 Amino acids lots APTTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGV VHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQH QETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQ GARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQ VTFVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQAL WQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRF EMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFL PPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQP WEEIKTSYAGVKEKYLSEFCFSGTYI LSLLQQGYHFTADSWEHI HFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 218 DNA GCCCCTACCACCCAGAACAAGGCCCTGCCCGAGAACGTGAA GTACGGCATCGTGCTGGATGCCGGCAGCAGCCACACCAGCC TGTACATCTACAAGTGGCCTGCCGAGAAAGAAAACGACACC GGCGTGGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGGCCC TGGCATCAGCAAGTTCGTGCAGAAAGTGAACGAGATCGGCA TCTACCTGACCGACTGCATGGAACGGGCCATG GAAGTGATC CCCAGAAGCCAGCACCAGGAAACCCCCGTGTATCTGGGAGC CACCGCCGGCATGAGACTGCTGAGAATGGAAAGCGAGGAAC TGGCCGACCGGGTGCTGGACGTGGTGGAAAGAAGCCTGAGC AACTACCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGC CAGGAAGAAGGCGCCTACGGCTGGATCACCATCAACTACCT GCTGGGCAAGTTCAGCCAGAAGA ATCAGGAAACCTTTCGGCG CCCTGGACCTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGC CCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCTGCAG TTCCGGCTGTACGGCAAGGACTACAATGTGTACACCCACAG CTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGGCAGAAGCT GGCCAAGGACATCCAGGTGGCCAGCAACGATCCTGCGGG ACCCTTGCTTCCACCCC GGCTACAAGAAAGTCGTGAACGTGT CCGACCTGTACAAGACCCCCTGCACCAAGAGATTCGAGATG ACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAAT TACCAGCAGTGCCACCAGAGCATCCTGGAACTGTTCAACAC

- 137 046596

CAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGGCATCTT CCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTT CTACTTCGTGATGAAGTTCCTGAACCTGACCAGCGAGAAGGT GTCCCAGGAAAAAGTGACAGAGATGATGAAGAAGTTCTGCG CCCAGCCCTGGGAGGAAATCAAGACCTCTACGCTGGCGTG AAAGAGAAGTACCTGAGCGAGTTCTGCTTCA GCGGCACCTA CATCCTGAGCCTGCTGCAGCAGGGCTACCACTTCACCGCCGA TAGCTGGGAGCACATCCACTTCATCGGCAAGATTCAGGGCA GCGACGCCGGCTGGACACTGGGCTACATGCTGAATCTGACC AACATGATCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAG CCACAGCACC ΕΡ1χΕΡ17χ EP19aal-6 SEQ ID NO: 219 Amino acids lots APTSSSTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDT GVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRS QHQETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPF DFQGARIITGQEEGAYGWrriNYLLGKFSQKNQETFGALDLGGA STQVTFVPQNQT IESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEKY LSEFCFSGTYILSLLQQGYHFTADSWE HIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 220 DNA GCCCCTACCAGCAGCAGCACCCAGAACAAGGCCCTGCCCGA GAACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCC ACACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAA AACGACACCGGCGTGGTGCATCAGGTGGAAGAGTGCAGAGT GAAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACG AGATCGGCATCTACCTGACCGACTGCATG GAACGGGCCATG GAAGTGATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGTA TCTGGGAGCCACCGCCGGCATGAGACTGCTGAGAATGGAAA GCGAGGAACTGGCCGACCGGGTGCTGGACGTGGTGGAAAGA AGCCTGAGCAACTACCCATTCGATTTTCAAGGCGCCAGAATC ATCACCGGCCAGGAAGAAGGCGCCTACGGCTGGATCACCAT CAACTACCTGCTGGGCAAGTTCAGC CAGAAGAATCAGGAAA

- 138 046596

CCTTCGGCGCCCTGGACCTGGGCGGAGCTTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGG CAGAAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGAT CCTGCGGGACCCTTGCTTCCACCCCGGCTACAAG AAAGTCGT GAACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGAT TCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCA TCGGCAATTACCAGCAGTGCCACCAGAGCATCCTGGAACTG TTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAAC GGCATCTTCCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTC AGCGCCTTCTACTTCGTGAT GAAGTTCCTGAACCTGACCAGC GAGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGA AGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTAC GCTGGCGTGAAAGAGAAGTACCTGAGCGAGTTCTGCTTCAG CGGCACCTACATCCTGAGCCTGCTGCAGCAGGGCTACCACTT CACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGA TTCAGGGCAGCGACGCCGGCT GGACACTGGGCTACATGCTG AATCTGACCAACATGATCCCCGCCGAGCAGCCCCTGAGCAC ACCTCTGAGCCACAGCACC EP1xEP14a al-3 SEQ ID NO: 221 Amino acids lots APTTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGV VHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQH QETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQ GARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQ VTFVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQAL WQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRF EMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFL PPLQGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQP WEEIKTSYAGVKEKYLSEYCFSGTYIL SLLLQGYHFTADSWEHI HFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 222 DNA GCCCCTACCACCCAGAACAAGGCCCTGCCCGAGAACGTGAA GTACGGCATCGTGCTGGATGCCGGCAGCAGCCACACCAGCC TGTACATCTACAAGTGGCCTGCCGAGAAAGAAAACGACACC

- 139 046596

GGCGTGGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGGCCC TGGCATCAGCAAGTTCGTGCAGAAAGTGAACGAGATCGGCA TCTACCTGACCGACTGCATGGAACGGGCCATGGAAGTGATC CCCAGAAGCCAGCACCAGAAACCCCCGTGTATCTGGGAGC CACCGCCGGCATGAGACTGCTGAGAATGGAAAGCGAGGAAC TGGCCGACCGGGTGCTGGACGTGGTG GAAAGAAGCCTGAGC AACTACCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGC CAGGAAGAAGGCGCCTACGGCTGGATCACCATCAACTACCT GCTGGGCAAGTTCAGCCAGAAGAATCAGGAAACCCTTCGGCG CCTTGGACCTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGC CCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCTGCAG TTCCGGCTGTACGGCAA ACTACAATGTGTACACCCACAG CTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGGCAGAAGCT GGCCAAGGACATCCAGGTGGCCAGCAACGAGATCCTGCGGG ACCCTTGCTTCCACCCCGGCTACAAGAAAGTCGTGAACGTGT CCGACCTGTACAAGACCCCCTGCACCAAGATTCGAGATG ACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAAT CCACCAGAGCATCCTGGAACTGTTCAACAC CAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGGCATCTT CCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTT CTACTCCGTGATGAAGTTCCTGAACCTGACCAGCGAGAAGG TGTCCCAGGAAAAAGTGACAGAGATGATGAAGAAGTTCTGC GCCCAGCCCTGGGAGGAAATCAAGACCTCCTACGCTGGCGT GAAA GAGAAGTACCTGAGCGAGTACTGCTTCAGCGGCACCT ACATCCTGAGCCTGCTGCTGCAGGGCTACCACTTCACCGCCG ATAGCTGGGAGCACATCCACTTCATCGGCAAGATTCAGGGC AGCGACGCCGGCTGGACACTGGGTTACATGCTGAATCTGAC CAACATGATCCCCGCCGAGCAGCCCCTGAGCACACCTCTGA GCCACAGCACC EP1xEP14a al-6 SEQ ID NO: 223 Amino acids lots APTSSSTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDT GVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRS QHQETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPF DFQGARIITGQEEGAYGWrriNYLLGKFSQKNQETFGALDLGGA

- 140 046596

STQVTFVPQNQTIESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEE IKTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWE HIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 224 DNA GCCCCTACCAGCAGCAGCACCCAGAACAAGGCCCTGCCCGA GAACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCC ACACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAA AACGACACCGGCGTGGTGCATCAGGTGGAAGAGTGCAGAGT GAAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACG AGATCGGCATCTACCTGACCGACTGCATG GAACGGGCCATG GAAGTGATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGTA TCTGGGAGCCACCGCCGGCATGAGACTGCTGAGAATGGAAA GCGAGGAACTGGCCGACCGGGTGCTGGACGTGGTGGAAAGA AGCCTGAGCAACTACCCATTCGATTTTCAAGGCGCCAGAATC ATCACCGGCCAGGAAGAAGGCGCCTACGGCTGGATCACCAT CAACTACCTGCTGGGCAAGTTCAGC CAGAAGAATCAGGAAA CCTTCGGCGCCTTGGACCTGGGCGGAGCTTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGG CAGAAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGAT CCTGCGGGACCCTTGCTTCC ACCCCGGCTACAAGAAAGTCGT GAACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGAT TCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCA TCGGCAATTACCAGCAGTGCCACCAGAGCATCCTGGAACTG TTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAAC GGCATCTTCCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTC TTCTACTCCGTGATGAAGTTCCTGAACCTGACCAGC GAGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGA AGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTAC GCTGGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCAG CGGCACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTT CACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGA

- 141 046596

TTCAGGGCAGCGACGCCGGCTGGACACTGGGTTACATGCTG AATCTGACCAACATGATCCCCGCCGAGCAGCCCCTGAGCAC ACCTCTGAGCCACAGCACC EP17xEP19 aal-3 SEQ ID NO: 225 Amino acids lots APTTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGV VHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQH QETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQ GARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQ VTFVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQAL WQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRF EMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFL PPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQP WEEIKTSYAGVKEKYLSEFCFSGTY ILSLLQQGYHFTADSWEHI HFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 226 DNA GCCCCTACCACCCAGAACAAGGCCCTGCCCGAGAACGTGAA GTACGGCATCGTGCTGGATGCCGGCAGCAGCCACACCAGCC TGTACATCTACAAGTGGCCTGCCGAGAAAGAAAACGACACC GGCGTGGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGGCCC TGGCATCAGCAAGTTCGTGCAGAAAGTGAACGAGATCGGCA TCTACCTGACCGACTGCATGGAACGGGCCAGG GAAGTGATC CCCAGAAGCCAGCACCAGGAAACCCCCGTGTATCTGGGAGC CACCGCCGGCATGAGACTGCTGAGAATGGAAAGCGAGGAAC TGGCCGACCGGGTGCTGGACGTGGTGGAAAGAAGCCTGAGC AACTACCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGC CAGGAAGAAGGCGCCTACGGCTGGATCACCATCAACTACCT GCTGGGCAAGTTCAGCCAGAAGA ATCAGGAAACCTTTCGGCG CCCTGGACCTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGC CCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCTGCAG TTCCGGCTGTACGGCAAGGACTACAATGTGTACACCCACAG CTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGGCAGAAGCT GGCCAAGGACATCCAGGTGGCCAGCAACGATCCTGCGGG ACCCTTGCTTCCACCCC GGCTACAAGAAAGTCGTGAACGTGT CCGACCTGTACAAGACCCCCTGCACCAAGAGATTCGAGATG ACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAAT

- 142 046596

TACCAGCAGTGCCACCAGAGCATCCTGGAACTGTTCAACAC CAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGGCATCTT CCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTT CTACTTCGTGATGAAGTTCCTGAACCTGACCAGCGAGAAGGT GTCCCAGGAAAAAGTGACAGAGATGATGAAGAAGTTCTGCG CCCAGCCCTGGGAGGAAATCAAGACCTCCTAC GCTGGCGTG AAAGAGAAGTACCTGAGCGAGTTTTGCTTCAGCGGCACCTA CATCCTGAGCCTGCTGCAGCAGGGCTACCACTTCACCGCCGA TAGCTGGGAGCACATCCACTTCATCGGCAAGATTCAGGGCA GCGACGCCGGCTGGACACTGGGCTACATGCTGAATCTGACC AACATGATCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAG CCACAGCACC EP17xEP19 aal-6 SEQ ID NO: 227 Aminokis lots APTSSSTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDT GVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRS QHQETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPF DFQGARIITGQEEGAYGWrriNYLLGKFSQKNQETFGALDLGGA STQVTFVPQNQ TIESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEK YLSEFCFSGTYILSLLQQGYHFTADSWE HIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 228 DNA GCCCCTACCAGCAGCAGCACCCAGAACAAGGCCCTGCCCGA GAACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCC ACACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAA AACGACACCGGCGTGGTGCATCAGGTGGAAGAGTGCAGAGT GAAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACG AGATCGGCATCTACCTGACCGACTGCATG GAACGGGCCAGG GAAGTGATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGTA TCTGGGAGCCACCGCCGGCATGAGACTGCTGAGAATGGAAA GCGAGGAACTGGCCGACCGGGTGCTGGACGTGGTGGAAAGA AGCCTGAGCAACTACCCATTCGATTTTCAAGGCGCCAGAATC ATCACCGGCCAGGAAGAAGGCGCCTACGGCTGGATCACCAT

- 143 046596

CAACTACCTGCTGGGCAAGTTCAGCCAGAAGAATCAGGAAA CCTTCGGCGCCCTGGACCTGGGCGGAGCTTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGG CAGAAGCTGGCCAAGGACATCCAGGTGGCCAGCAA CGAGAT CCTGCGGGACCCTTGCTTCCACCCCGGCTACAAGAAAGTCGT GAACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGAT TCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCA TCGGCAATTACCAGCAGTGCCACCAGAGCATCCTGGAACTG TTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAAC GGCATCTTCCTGCCACCTCTGCAGG GGGATTTCGGCGCCTTC AGCGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAGC GAGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGA AGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTAC GCTGGCGTGAAAGAGAAGTACCTGAGCGAGTTTTGCTTCAG CGGCACCTACATCCTGAGCCTGCTGCAGCAGGGCTACCACTT CACCGCCGATAGCTGGGAGCA CATCCACTTCATCGGCAAGA TTCAGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCTG AATCTGACCAACATGATCCCCGCCGAGCAGCCCCTGAGCAC ACCTCTGAGCCACAGCACC EP14aal-3 SEQ ID NO: 229 Amino acids lots APTTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGV VHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQH QETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQ GARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQ VTFVPQNQTIESPDNALQ WEEIKTSYAGVKEKYLSEYCFSGTY ILSLLLQGYHFTADSWEHI HFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 230 DNA GCCCCTACCACCCAGAACAAGGCCCTGCCCGAGAACGTGAA GTACGGCATCGTGCTGGACGCCGGCTCCTCCCACACCTCCCT GTACATCTACAAGTGGCCTGCCGAGAAAGAAAACGACACCG

- 144 046596

GCGTGGTGCACCAAGTGGAAGAGTGCAGAGTGAAGGGCCCC GGCATCTCAAGTTCGTGCAGAAAGTGAACGAGATCGGCAT CTACCTGACCGACTGCATGGAACGGGCCAGAGAAGTGATCC CTCGGTCCCAGCACCAGGAAACCCCTGTCTACCTGGGCGCCA CCGCCGGCATGCGGCTGCTGCGGATGGAATCCGAGGAACTG GCCGACCGGGTGCTGGACGTGGTG GAACGGTCCCTGTCCAA CTACCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGCCA GGAAGAGGGCGCCTACGGCTGGATCACCATCAACTACCTGC TGGGCAAGTTCTCCCAGAAGAATCAGGAAACCTTTCGGCGCC CTGGACCTGGGCGGAGCCAGCACCCAAGTCACATTCGTGCC CCAGAACCAGACCATCGAGAGCCCCGACAACGCCCTGCAGT TCCGGCTGTACGGCAA GGACTACAACGTGTACACCCACAGC TTTCTGTGCTACGGCAAGGACCAGGCCCTGTGGCAGAAGCT GGCCAAGGACATCCAAGTGGCCTCCAACGAGATCCTGCGGG ACCCCTGCTTCCACCCCGGCTACAAGAAAGTGGTCAACGTGT CCGACCTGTACAAGACCCCTTGCACCAAGATTCGAGATG ACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAAC TGCCACCAGTCCATCCTGGAACTGTTCAACACC TCCTACTGCCCCTACTCCCAGTGCGCCTTCAACGGCATCTTC CTGCCTCCACTGCAGGGCGACTTCGGCGCCTTCTCCGCCTTC TACTCCGTGATGAAGTTCCTGAACCTGACCTCCGAGAAAGTG TCCCAGGAAAAAGTGACCGATGATGAAGAAGTTCTGCGC CCAGCCCTGGGAGGAAATCAAGACCTCCTACGCTGGCGTGA AAGAGAAGTACCTGTCCGAGTACTGCTTCTCCGGCACCTACA TCCTGTCCCTGCTGCTGCAGGGCTACCACTTCACCGCCGACA GCTGGAGCACATCCACTTCATCGGCAAGATCCAGGGATCC GACGCTGGCTGGACCCTGGGCTACATGCTGAATCTGACCAA CATGATCCCCGCCGAGCAGCCCCTGTCCACCCCTCTGTCTCA CTCCACC EP14aal-6 SEQ ID NO: 231 Amino acids lots APTSSSTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDT GVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRS QHQETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPF DFQGARIITGQEEGAYGWrriNYLLGKFSQKNQETFGALDLGGA STQVTFVPQNQ TIESPDNALQFRLYGKDYNVYTHSFLCYGKDQ

- 145 046596

ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEKYLSEYCFSGTYILSLLLQGYHFTADSWE HIHFIG KIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 232 DNA GCCCCTACCAGCAGCAGCACCCAGAACAAGGCCCTGCCCGA GAACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCC ACACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAA AACGACACCGGCGTGGTGCATCAGGTGGAAGAGTGCAGAGT GAAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACG AGATCGGCATCTACCTGACCGACTGCATG GAACGGGCCAGG GAAGTGATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGTA TCTGGGAGCCACCGCCGGCATGAGACTGCTGAGAATGGAAA GCGAGGAACTGGCCGACCGGGTGCTGGACGTGGTGGAAAGA AGCCTGAGCAACTACCCATTCGATTTTCAAGGCGCCAGAATC ATCACCGGCCAGGAAGAAGGCGCCTACGGCTGGATCACCAT CAACTACCTGCTGGGCAAGTTCAGC CAGAAGAATCAGGAAA CCTTCGGCGCCTTGGACCTGGGCGGAGCTTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGG CAGAAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGAT CCTGCGGGACCCTTGCTTCC ACCCCGGCTACAAGAAAGTCGT GAACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGAT TCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCA TCGGCAATTACCAGCAGTGCCACCAGAGCATCCTGGAACTG TTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAAC GGCATCTTCCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTC TTCTACTCCGTGATGAAGTTCCTGAACCTGACCAGC GAGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGA AGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTAC GCTGGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCAG CGGCACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTT CACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGA CAGCGACGCCGGCTGGACACTGGGTTACATGCTG

- 146 046596

AATCTGACCAACATGATCCCCGCCGAGCAGCCCCTGAGCAC ACCTCTGAGCCACAGCACC ΕΡ1χΕΡ14χ EP19aal-3 SEQ ID NO: 233 Amino acids lots APTTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGV VHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRSQH QETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQ GARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQ VTFVPQNQTIESPDNALQFR LYGKDYNVYTHSFLCYGKDQAL WQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRF EMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFL PPLQGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCAQP WEEIKTSYAGVKEKYLSEYCFSGTYI LSLLQQGYHFTADSWEHI HFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 234 DNA GCCCCTACCACCCAGAACAAGGCCCTGCCCGAGAACGTGAA GTACGGCATCGTGCTGGATGCCGGCAGCAGCCACACCAGCC TGTACATCTACAAGTGGCCTGCCGAGAAAGAAAACGACACC GGCGTGGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGGCCC TGGCATCAGCAAGTTCGTGCAGAAAGTGAACGAGATCGGCA TCTACCTGACCGACTGCATGGAACGGGCCATG GAAGTGATC CCCAGAAGCCAGCACCAGGAAACCCCCGTGTATCTGGGAGC CACCGCCGGCATGAGACTGCTGAGAATGGAAAGCGAGGAAC TGGCCGACCGGGTGCTGGACGTGGTGGAAAGAAGCCTGAGC AACTACCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGC CAGGAAGAAGGCGCCTACGGCTGGATCACCATCAACTACCT GCTGGGCAAGTTCAGCCAGAAGA ATCAGGAAACCTTTCGGCG CCCTGGACCTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGC CCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCTGCAG TTCCGGCTGTACGGCAAGGACTACAATGTGTACACCCACAG CTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGGCAGAAGCT GGCCAAGGACATCCAGGTGGCCAGCAACGATCCTGCGGG ACCCTTGCTTCCACCCC GGCTACAAGAAAGTCGTGAACGTGT CCGACCTGTACAAGACCCCCTGCACCAAGAGATTCGAGATG ACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAAT TACCAGCAGTGCCACCAGAGCATCCTGGAACTGTTCAACAC

- 147 046596

CAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGGCATCTT CCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTT CTACTCCGTGATGAAGTTCCTGAACCTGACCAGCGAGAAGG TGTCCCAGGAAAAAGTGACAGAGATGATGAAGAAGTTCTGC GCCCAGCCCTGGGAGGAAATCAAGACCTCTACGCTGGCGT GAAAGAGAAGTACCTGAGCGGTACTGCTTC AGCGGCACCT ACATCCTGAGCCTGCTGCAGCAGGGCTACCACTTCACCGCCG ATAGCTGGGAGCACATCCACTTCATCGGCAAGATTCAGGGC AGCGACGCCGGCTGGACACTGGGCTACATGCTGAATCTGAC CAACATGATCCCCGCCGAGCAGCCCCTGAGCACACCTCTGA GCCACAGCACC ΕΡ1χΕΡ14χ EP19aal-6 SEQ ID NO: 235 Amino acids lots APTSSSTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDT GVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAMEVIPRS QHQETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPF DFQGARIITGQEEGAYGWrriNYLLGKFSQKNQETFGALDLGGA STQVTFVPQNQT IESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYSVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEKY LSEYCFSGTYILSLLQQGYHFTADSW EHIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 236 DNA GCCCCTACCAGCAGCAGCACCCAGAACAAGGCCCTGCCCGA GAACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCC ACACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAA AACGACACCGGCGTGGTGCATCAGGTGGAAGAGTGCAGAGT GAAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACG AGATCGGCATCTACCTGACCGACTGCATG GAACGGGCCATG GAAGTGATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGTA TCTGGGAGCCACCGCCGGCATGAGACTGCTGAGAATGGAAA GCGAGGAACTGGCCGACCGGGTGCTGGACGTGGTGGAAAGA AGCCTGAGCAACTACCCATTCGATTTTCAAGGCGCCAGAATC ATCACCGGCCAGGAAGAAGGCGCCTACGGCTGGATCACCAT CAACTACCTGCTGGGCAAGTTCAGC CAGAAGAATCAGGAAA

- 148 046596

CCTTCGGCGCCCTGGACCTGGGCGGAGCTTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGG CAGAAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGAT CCTGCGGGACCCTTGCTTCCACCCCGGCTACAAG AAAGTCGT GAACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGAT TCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCA TCGGCAATTACCAGCAGTGCCACCAGAGCATCCTGGAACTG TTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAAC GGCATCTTCCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTC AGCGCCTTCTACTCCGTGAT GAAGTTCCTGAACCTGACCAGC GAGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGA AGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTAC GCTGGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCAG CGGCACCTACATCCTGAGCCTGCTGCAGCAGGGCTACCACTT CACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGA TTCAGGGCAGCGACGCCGGCT GGACACTGGGCTACATGCTG AATCTGACCAACATGATCCCCGCCGAGCAGCCCCTGAGCAC ACCTCTGAGCCACAGCACC EP17aal-3 SEQ ID NO: 237 Amino acids lots APTTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGV VHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQH QETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQ GARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQ VTFVPQNQTIESPDNALQ FRLYGKDYNVYTHSFLCYGKDQAL WQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTKRF EMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGIFL PPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCAQP WEEIKTSYAGVNEKYLSEFCFSGTYIL SLLLQGYHFTADSWEHI HFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 238 DNA GCCCCTACCACCCAGAACAAGGCCCTGCCCGAGAACGTGAA GTACGGCATCGTGCTGGATGCCGGCAGCAGCCACACCAGCC TGTACATCTACAAGTGGCCTGCCGAGAAAGAAAACGACACC GGCGTGGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGGCCC

- 149 046596

TGGCATCAGCAAGTTCGTGCAGAAAGTGAACGAGATCGGCA TCTACCTGACCGACTGCATGGAACGGGCCAGGGAAGTGATC CCCAGAAGCCAGCACCAGGAAACCCCCGTGTATCTGGGAGC CACCGCCGGCATGAGACTGCTGAGAATGGAAAGCGAGGAAC TGGCCGACCGGGTGCTGGACGTGGTGGAAAGAAGCCTGAGC AACTACCCATTCGATTTTCAAGGCGCCA GAATCATCACCGGC CAGGAAGAAGGCGCCTACGGCTGGATCACCATCAACTACCT GCTGGGCAAGTTCAGCCAGAAGAATCAGGAAACCCTTCGGCG CCCTGGACCTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGC CCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCTGCAG TTCCGGCTGTACGGCAAGGACTACAATGTGTACACCCACAG CTTTCTGTGCTACGGAAAGGA CCAGGCTCTGTGGCAGAAGCT GGCCAAGGACATCCAGGTGGCCAGCAACGATCCTGCGGG ACCCTTGCTTCCACCCCGGCTACAAGAAAGTCGTGAACGTGT CCGACCTGTACAAGACCCCCTGCACCAAGAGATTCGAGATG ACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAAT TACCAGCAGTGCCACCAGAGCATCCTGGAACTGTTCAACAC CAGCTACTGCCCCT ACAGCCAGTGCGCCTTCAACGGCATCTT CCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTT CTACTTCGTGATGAAGTTCCTGAACCTGACCAGCGAGAAGGT GTCCCAGGAAAAAGTGACAGAGATGATGAAGAAGTTCTGCG CCCAACCCTGGGAGGAAATCAAGACCTCCTACGCTGGCGTG AACGAGAAGTACCTGAGCGAGTTTTGCTTCAGCGGCACCTA CATCC TGAGCCTGCTGCTGCAGGGCTACCACTTCACCGCCGA TAGCTGGGAGCACATCCACTTCATCGGCAAGATTCAGGGCA GCGACGCCGGCTGGACACTGGGCTACATGCTGAATCTGACC AACATGATCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAG CCACAGCACC EP17aal-6 SEQ ID NO: 239 Amino acids lots APTSSSTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDT GVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRS QHQETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPF DFQGARIITGQEEGAYGWrriNYLLGKFSQKNQETFGALDLGGA STQVTFVPQNQ TIESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK

- 150 046596

RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVNEKYLSEFCFSGTYILSLLLQGYHFTADSWE HIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 240 DNA GCCCCTACCAGCAGCAGCACCCAGAACAAGGCCCTGCCCGA GAACGTGAAGTACGGCATCGTGCTGGATGCCGGCAGCAGCC ACACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAA AACGACACCGGCGTGGTGCATCAGGTGGAAGAGTGCAGAGT GAAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACG AGATCGGCATCTACCTGACCGACTGCATG GAACGGGCCAGG GAAGTGATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGTA TCTGGGAGCCACCGCCGGCATGAGACTGCTGAGAATGGAAA GCGAGGAACTGGCCGACCGGGTGCTGGACGTGGTGGAAAGA AGCCTGAGCAACTACCCATTCGATTTTCAAGGCGCCAGAATC ATCACCGGCCAGGAAGAAGGCGCCTACGGCTGGATCACCAT CAACTACCTGCTGGGCAAGTTCAGC CAGAAGAATCAGGAAA CCTTCGGCGCCCTGGACCTGGGCGGAGCTTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGG CAGAAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGAT CCTGCGGGACCCTTGCTTCC ACCCCGGCTACAAGAAAGTCGT GAACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGAT TCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCA TCGGCAATTACCAGCAGTGCCACCAGAGCATCCTGGAACTG TTCAACACCAGCTACTGCCCCTACAGCCAGTGCGCCTTCAAC GGCATCTTCCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTC TTCTACTTCGTGATGAAGTTCCTGAACCTGACCAGC GAGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGA AGTTCTGCGCCCAACCCTGGGAGGAAATCAAGACCTCCTAC GCTGGCGTGAACGAGAAGTACCTGAGCGAGTTTTGCTTCAG CGGCACCTACATCCTGAGCCTGCTGCTGCAGGGCTACCACTT CACCGCCGATAGCTGGGAGCACATCCACTTCATCGGCAAGA GGCAGCGACGCCGGCTGGACACTGGGCTACATGCTG AATCTGACCAACATGATCCCCGCCGAGCAGCCCCTGAGCAC

- 151 046596

ACCTCTGAGCCACAGCACC EP17aal- 15 SEQ ID NO: 241 Amino acids lots APTSSSTKKTQLTSSTQNKALPENVKYGIVLDAGSSHTSLYIYK WPAEKENDTGVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCM ERAREVIPRSQHQETPVYLGATAGMRLLRMESEELADRVLDVV ERSLSNYPFDFQGARIITGQEEGAYGWITINYLLGKFSQKNQETF GALDLGGASTQV TFVPQNQTIESPDNALQFRLYGKDYNVYTHS FLCYGKDQALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVS DLYKTPCTKRFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCP YSQCAFNGIFLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVT EMMKKFCAQPWEEIKTSY AGVNEKYLSEFCFSGTYILSLLLQG YHFTADSWEHIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLS TPLSHST SEQ ID NO: 242 DNA GCCCCTACCAGCAGCAGCACCAAGAAAACCCAGCTGACCAG CAGCACCCAGAACAAGGCCCTGCCCGAGAACGTGAAGTACG GCATCGTGCTGGATGCCGGCAGCAGCCACACCAGCCTGTAC ATCTACAAGTGGCCTGCCGAAAGAAAACGACACCGGCGT GGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGGCCCTGGCA TCAGCAAGTTCGTGCAGAAAGTGAACGAGA TCGGCATCTAC CTGACCGACTGCATGGAACGGGCCAGGGAAGTGATCCCCAG AAGCCAGCACCAGGAAACCCCCGTGTATCTGGGAGCCACCG CCGGCATGAGACTGCTGAGAATGGAAAGCGAGGAACTGGCC GACCGGGTGCTGGACGTGGTGGAAAGAAGCCTGAGCAACTA CCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGCCAGGA AGAAGGCGCCTACGGCTGGATCACCATCA ACTACCTGCTGG GCAAGTTCAGCCAGAAGAATCAGGAAACCTTCGGCGCCCTG GACCTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGCCCCAG AATCAGACCATCGAGAGCCCCGACAACGCCCTGCAGTTCCG GCTGTACGGCAAGGACTACAATGTGTACACCCACAGCTTTCT GTGCTACGGAAAGGACCAGGCTCTGTGGCAGAAGCTGGCCA AGGACATCCAGGTGGCC AGCAACGAGATCCTGCGGGACCCT TGCTTCCACCCCGGCTACAAGAAAGTCGTGAACGTGTCCGAC CTGTACAAGACCCCCTGCACCAAGAGATTCGAGATGACCCT GCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAATTACCA

- 152 046596

GCAGTGCCACCAGAGCATCCTGGAACTGTTCAACACCAGCT ACTGCCCCTACAGCCAGTGCGCCTTCAACGGCATCTTCCTGC CACCTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTTCTACT TCGTGATGAAGTTCCTGAACCTGACCAGCGAGAAGGTGTCC CAGGAAAAAGTGACAGAGATGATGAAAGTTCTGCGCCCA ACCCTGGGAGGAAATCAAGACCTCCTACGCTGG CGTGAACG AGAAGTACCTGAGCGAGTTTTGCTTCAGCGGCACCTACATCC TGAGCCTGCTGCTGCAGGGCTACCACTTCACCGCCGATAGCT GGGAGCACATCCACTTCATCGGCAAGATTCAGGGCAGCGAC GCCGGCTGGACACTGGGCTACATGCTGAATCTGACCAACAT GATCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAGCCACA GCACC EP19aal-3 SEQ ID NO: 243 Amino acids lots APTTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDTGV VHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRSQH QETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPFDFQ GARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGASTQ VTFVPQNQTIESPDNALQ WEEIKTSYAGVKEKYLSEYCFSGTY ILSLLQQGYHFTADSWEDI HFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 244 DNA GCCCCTACCACCCAGAACAAGGCCCTGCCCGAGAACGTGAA GTACGGCATCGTGCTGGATGCCGGCAGCAGCCACACCAGCC TGTACATCTACAAGTGGCCTGCCGAGAAAGAAAACGACACC GGCGTGGTGCATCAGGTGGAAGAGTGCAGAGTGAAGGGCCC TGGCATCAGCAAGTTCGTGCAGAAAGTGAACGAGATCGGCA TCTACCTGACCGACTGCATGGAACGGGCCAGG GAAGTGATC CCCAGAAGCCAGCACCAGGAAACCCCCGTGTATCTGGGAGC CACCGCCGGCATGAGACTGCTGAGAATGGAAAGCGAGGAAC TGGCCGACCGGGTGCTGGACGTGGTGGAAAGAAGCCTGAGC AACTACCCATTCGATTTTCAAGGCGCCAGAATCATCACCGGC CAGGAAGAAGGCGCCTACGGCTGGATCACCATCAACTACCT GCTGGGCAAGTTCAGCCAGAAGA ATCAGGAAACCTTTCGGCG

- 153 046596

CCCTGGACCTGGGCGGAGCTTCTACCCAAGTGACCTTCGTGC CCCAGAATCAGACCATCGAGAGCCCCGACAACGCCCTGCAG TTCCGGCTGTACGGCAAGGACTACAATGTGTACACCCACAG CTTTCTGTGCTACGGAAAGGACCAGGCTCTGTGGCAGAAGCT GGCCAAGGACATCCAGGTGGCCAGCAACGATCCTGCGGG ACCCTTGCTTCCACCCCGCTACAAGAAAGTC GTGAACGTGT CCGACCTGTACAAGACCCCCTGCACCAAGAGATTCGAGATG ACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCATCGGCAAT TACCAGCAGTGCCACCAGAGCATCCTGGAACTGTTCAACAC CAGCTACTGCCCCTACAGCCAGTGCGCCTTCAACGGCATCTT CCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTCAGCGCCTT CTACTTCGTGATGAAGTTCCTGA ACCTGACCAGCGAGAAGGT GTCCCAGGAAAAAGTGACAGAGATGATGAAGAAGTTCTGCG CCCAGCCCTGGGAGGAAATCAAGACCTCTACGCTGGCGTG AAAGAAGTACCTGAGCGAGTACTGCTTCAGCGGCACCTA CATCCTGAGCCTGCTGCAGCAGGGCTACCACTTCACCGCCGA TAGCTGGGAGGACATCCACTTCATCGGCAAGATTCAGGGCA GCGACGCCGGCTGGAC ACTGGGCTACATGCTGAATCTGACC AACATGATCCCCGCCGAGCAGCCCCTGAGCACACCTCTGAG CCACAGCACC EP19aal-6 SEQ ID NO: 245 Amino acids lots APTSSSTQNKALPENVKYGIVLDAGSSHTSLYIYKWPAEKENDT GVVHQVEECRVKGPGISKFVQKVNEIGIYLTDCMERAREVIPRS QHQETPVYLGATAGMRLLRMESEELADRVLDVVERSLSNYPF DFQGARIITGQEEGAYGWITINYLLGKFSQKNQETFGALDLGGA STQVTFVPQNQT IESPDNALQFRLYGKDYNVYTHSFLCYGKDQ ALWQKLAKDIQVASNEILRDPCFHPGYKKVVNVSDLYKTPCTK RFEMTLPFQQFEIQGIGNYQQCHQSILELFNTSYCPYSQCAFNGI FLPPLQGDFGAFSAFYFVMKFLNLTSEKVSQEKVTEMMKKFCA QPWEEIKTSYAGVKEKY LSEYCFSGTYILSLLQQGYHFTADSW EDIHFIGKIQGSDAGWTLGYMLNLTNMIPAEQPLSTPLSHST SEQ ID NO: 246 DNA GCCCCTACCAGCAGCAGCACCCAGAACAAGGCCCTGCCCGA GAACGTGAAGTACGGCATCGTGCTGGATGCCCGGCAGCAGCC ACACCAGCCTGTACATCTACAAGTGGCCTGCCGAGAAAGAA AACGACACCGGCGTGGTGCATCAGGTGGAAGAGTGCAGAGT

- 154 046596

GAAGGGCCCTGGCATCAGCAAGTTCGTGCAGAAAGTGAACG AGATCGGCATCTACCTGACCGACTGCATGGAACGGGCCAGG GAAGTGATCCCCAGAAGCCAGCACCAGGAAACCCCCGTGTA TCTGGGAGCCACCGCCGGCATGAGACTGCTGAGAATGGAAA GCGAGGAACTGGCCGACCGGGTGCTGGACGTGGTGGAAAGA AGCCTGAGCAACTACCCATTCGATTTTCAAG GCGCCAGAATC ATCACCGGCCAGGAAGAAGGCGCCTACGGCTGGATCACCAT CAACTACCTGCTGGGCAAGTTCAGCCAGAAGAATCAGGAAA CCTTCGGCGCCCTGGACCTGGGCGGAGCTTCTACCCAAGTGA CCTTCGTGCCCCAGAATCAGACCATCGAGAGCCCCGACAAC GCCCTGCAGTTCCGGCTGTACGGCAAGGACTACAATGTGTAC ACCCACAGCTTTCTGTGCTACGGAAAGGA CCAGGCTCTGTGG CAGAAGCTGGCCAAGGACATCCAGGTGGCCAGCAACGAGAT CCTGCGGGACCCTTGCTTCCACCCCGGCTACAAGAAAGTCGT GAACGTGTCCGACCTGTACAAGACCCCCTGCACCAAGAGAT TCGAGATGACCCTGCCCTTCCAGCAGTTCGAGATCCAGGGCA TCGGCAATTACCAGCAGTGCCACCAGAGCATCCTGGAACTG TTCAACACCAGCTACTGC CCCTACAGCCAGTGCGCCTTCAAC GGCATCTTCCTGCCACCTCTGCAGGGGGATTTCGGCGCCTTC AGCGCCTTCTACTTCGTGATGAAGTTCCTGAACCTGACCAGC GAGAAGGTGTCCCAGGAAAAAGTGACAGAGATGATGAAGA AGTTCTGCGCCCAGCCCTGGGAGGAAATCAAGACCTCCTAC GCTGGCGTGAAAGAGAAGTACCTGAGCGAGTACTGCTTCAG CGGCACCTACAT CCTGAGCCTGCTGCAGCAGGGCTACCACTT CACCGCCGATAGCTGGGAGGACATCCACTTCATCGGCAAGA TTCAGGGCAGCGACGCCGGCTGGACACTGGGCTACATGCTG AATCTGACCAACATGATCCCCGCCGAGCAGCCCCTGAGCAC ACCTCTGAGCCACAGCACC SEQ ID NO: 247 Amino acids lots EFRHDS SEQ ID NO: 248 DNA GAATTCCGGCACGACAGC SEQ ID NO: 249 Amino acids lots NNNNNNN SEQ ID DNA SATSATSATSATSAS NO: 250

- 155 046596

List of sequences <110> NOVARTIS AG <120> SOLUBILIZED APYRASES, METHODS AND APPLICATION <130> PAT057510-EP-EPA <140> EP 18184269.1 <141> 07/18/2018 <160> 253 <170> PatentIn version 3.5 <21 0> 1 < 211> 510 <212> PROTEIN <213> Homo sapiens <400> 1

Met Glu Asp Thr Lys Glu Ser Asn Val Lys Thr Phe Cys Ser Lys Asn

5 10 15

Ile Leu Ala Ile Leu Gly Phe Ser Ser Ile Ile Ala Val Ile Ala Leu 20 25 30

Leu Ala Val Gly Leu Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys 35 40 45

Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile 50 55 60

Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln 65 70 75 80

Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln 85 90 95

Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala

100 105 110

Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu

115 120 125

Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu

130 135 140

Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro 145 150 155 160

Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala

- 156 046596

165 170 175

Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys

180 185 190

Thr Arg Trp Phe Ser Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr

195 200 205

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

210 215 220

Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg

225 230 235 240

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

245 250 255

Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val

260 265 270

Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys

275 280 285

Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg

290 295 300

Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly

305 310 315 320

Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser

325 330 335

Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro

340 345 350

Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys

355 360 365

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

370 375 380

Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser

385 390 395 400

Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly

405 410 415

- 157 046596

Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp

420 425 430

Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala 435 440 445

Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala

450 455 460

Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr Tyr Val Phe Leu 465 470 475 480

Met Val Leu Phe Ser Leu Val Leu Phe Thr Val Ala Ile Ile Gly Leu

485 490 495

Leu Ile Phe His Lys Pro Ser Tyr Phe Trp Lys Asp Met Val

500 505 510 <210>2 <211> 511 <212> PROTEIN <213> Rattus norvegicus <400> 2

Met Glu Asp Ile Lys Asp Ser Lys Val Lys Arg Phe Cys Ser Lys Asn 1 5 10 15

Ile Leu Ile Ile Leu Gly Phe Ser Ser Val Leu Ala Val Ile Ala Leu 20 25 30

Ile Ala Val Gly Leu Thr His Asn Lys Pro Leu Pro Glu Asn Val Lys 35 40 45

Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Asn Leu Tyr Ile 50 55 60

Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val Gln Leu 65 70 75 80

Leu Glu Glu Cys Gln Val Lys Gly Pro Gly Ile Ser Lys Tyr Ala Gln 85 90 95

Lys Thr Asp Glu Ile Ala Ala Tyr Leu Ala Glu Cys Met Lys Met Ser

100 105 110

Thr Glu Arg Ile Pro Ala Ser Lys Gln His Gln Thr Pro Val Tyr Leu

115 120 125

- 158 046596

Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Lys Gln Ser

130 135 140

Ala Asp Glu Val Leu Ala Ala Val Ser Arg Ser Leu Lys Ser Tyr Pro 145 150 155 160

Phe Asp Phe Gln Gly Ala Lys Ile Ile Thr Gly Gln Glu Glu Gly Ala

165 170 175

Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Arg Phe Thr Gln Glu

180 185 190

Gln Ser Trp Leu Asn Phe Ile Ser Asp Ser Gln Lys Gln Ala Thr Phe

195 200 205

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

210 215 220

Leu Asn Gln Thr Leu Glu Ala Pro Glu Thr Ser Leu Gln Phe Arg Leu

225 230 235 240

Tyr Gly Thr Asp Tyr Thr Val Tyr Thr His Ser Phe Leu Cys Tyr Gly

245 250 255

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Gln Asp Ile Gln Val Ser

260 265 270

Ser Gly Gly Ile Leu Lys Asp Pro Cys Phe Tyr Pro Gly Tyr Lys Lys 275 280 285

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

290 295 300

Glu Lys Lys Leu Pro Phe Asn Gln Phe Gln Val Gln Gly Thr Gly Asp

305 310 315 320

Tyr Glu Gln Cys His Gln Ser Ile Leu Lys Phe Phe Asn Asn Ser His

325 330 335

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Val Phe Leu Pro Pro Leu

340 345 350

Gln Gly Ser Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Asp Phe

355 360 365

Phe Lys Lys Met Ala Asn Asp Ser Val Ser Ser Gln Glu Lys Met Thr

- 159 046596

370 375 380

Glu Ile Thr Lys Asn Phe Cys Ser Lys Pro Trp Glu Glu Val Lys Ala

385 390 395 400

Ser Tyr Pro Thr Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser 405 410 415

Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr Asn Phe Thr Gly

420 425 430

Thr Ser Trp Asp Gln Ile His Phe Met Gly Lys Ile Lys Asp Ser Asn

435 440 445

Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro

450 455 460

Ala Glu Gln Pro Leu Ser Pro Pro Leu Pro His Ser Thr Tyr Ile Ser

465 470 475 480

Leu Met Val Leu Phe Ser Leu Val Leu Val Ala Met Val Ile Thr Gly

485 490 495

Leu Phe Ile Phe Ser Lys Pro Ser Tyr Phe Trp Lys Glu Ala Val

500 505 510 <210>3 <211> 441 <212> PROTEIN <213> Homo sapiens <400> 3

Gln Ile His Lys Gln Glu Val Leu Pro Pro Gly Leu Lys Tyr Gly Ile 1 5 10 15

Val Leu Asp Ala Gly Ser Ser Arg Thr Thr Val Tyr Val Tyr Gln Trp 20 25 30

Pro Ala Glu Lys Glu Asn Asn Thr Gly Val Val Ser Gln Thr Phe Lys 35 40 45

Cys Ser Val Lys Gly Ser Gly Ile Ser Ser Tyr Gly Asn Asn Pro Gln 50 55 60

Asp Val Pro Arg Ala Phe Glu Glu Cys Met Gln Lys Val Lys Gly Gln 65 70 75 80

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

- 160 046596

90 95

Ala Gly Met Arg Leu Leu Arg Leu Gln Asn Glu Thr Ala Ala Asn Glu

100 105 110

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

115 120 125

Arg Gly Ala Gln Ile Ile Ser Gly Gln Glu Glu Gly Val Tyr Gly Trp

130 135 140

Ile Thr Ala Asn Tyr Leu Met Gly Asn Phe Leu Glu Lys Asn Leu Trp 145 150 155 160

His Met Trp Val His Pro His Gly Val Glu Thr Thr Gly Ala Leu Asp

165 170 175

Leu Gly Gly Ala Ser Thr Gln Ile Ser Phe Val Ala Gly Glu Lys Met

180 185 190

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

195 200 205

Tyr Thr Leu Tyr Thr His Ser Phe Gln Cys Tyr Gly Arg Asn Glu Ala

210 215 220

Glu Lys Lys Phe Leu Ala Met Leu Leu Gln Asn Ser Pro Thr Lys Asn

225 230 235 240

His Leu Thr Asn Pro Cys Tyr Pro Arg Asp Tyr Ser Ile Ser Phe Thr

245 250 255

Met Gly His Val Phe Asp Ser Leu Cys Thr Val Asp Gln Arg Pro Glu

260 265 270

Ser Tyr Asn Pro Asn Asp Val Ile Thr Phe Glu Gly Thr Gly Asp Pro 275 280 285

Ser Leu Cys Lys Glu Lys Val Ala Ser Ile Phe Asp Phe Lys Ala Cys 290 295 300

His Asp Gln Glu Thr Cys Ser Phe Asp Gly Val Tyr Gln Pro Lys Ile

305 310 315 320

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

325 330 335

- 161 046596

Leu Asn Leu Ser Gly Ser Phe Ser Leu Asp Thr Phe Asn Ser Ser Thr

340 345 350

Trp Asn Phe Cys Ser Gln Asn Trp Ser Gln Leu Pro Leu Leu Leu Pro

355 360 365

Lys Phe Asp Glu Val Tyr Ala Arg Ser Tyr Cys Phe Ser Ala Asn Tyr

370 375 380

Ile Tyr His Leu Phe Val Asn Gly Tyr Lys Phe Thr Glu Glu Thr Trp 385 390 395 400

Pro Gln Ile His Phe Glu Lys Glu Val Gly Asn Ser Ser Ile Ala Trp

405 410 415

Ser Leu Gly Tyr Met Leu Ser Leu Thr Asn Gln Ile Pro Ala Glu Ser 420 425 430

Pro Leu Ile Arg Leu Pro Ile Glu Pro 435 440 <210>4 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 4

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

- 162 046596

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

- 163 046596

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly

385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210>5 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 5 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900

- 164 046596 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatca agacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatg ct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 < 210>6 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 6

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

- 165 046596

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

- 166 046596

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210>7 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 7 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260

- 167 046596 acacctctga gccacagcac c 1281 <210>8 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 8

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Met

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

- 168 046596

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210>9 <211> 1281 <212> DNA

- 169 046596 <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 9 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgatggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccaaggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 10 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 10

- 170 046596

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

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

245 250 255

- 171 046596

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Arg Thr Pro Leu Ser His Ser Thr 420 425 <210> 11 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 11 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180

- 172 046596 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tgg tggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcg tgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agggattc ga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcc t tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggca g cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgcgc 1260 acacctctga gccacagcac c 1281 <210> 12 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 12

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Ala Gln Lys Val Asn Glu Ile

- 173 046596

55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

- 174 046596

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Arg Thr Pro Leu Ser His Ser Thr 420 425 <210> 13 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400>13 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgcgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600

- 175 046596 acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagatt cga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcg cct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggca aga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagg 1260 acacctctga gccacagcac c 1281 <210> 14 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 14

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Met

100 105 110

- 176 046596

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

- 177 046596

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Asp Lys Ile Gln Gly Ser Asp Ala Gly

385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 15 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 15 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgatggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960

- 178 046596 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcgacaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 12 81 <210> 16 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 16

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Ser Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Met

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

- 179 046596

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Arg Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

- 180 046596

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 17 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 17 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatctc cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgatggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgc ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281

- 181 046596 <210> 18 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 18

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Glu Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Ser Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

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

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

- 182 046596

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Thr Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 19 <211> 1281 <212> DNA <213> Artificial sequence <220>

- 183 046596 <221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 19 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgagg aagaaaacga caccggc gtg 120 gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgtccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg cggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcct ac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta ca atgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcacc ggcaattacc agcagtgcca ccagagcatc 84 0 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga t gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacc tctga gccacagcac c 1281 <210> 20 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 20

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

- 184 046596

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

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

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

- 185 046596

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 21 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 21 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgattccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300

- 186 046596 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg cggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggt aagttcagcc agaagaat ca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggctct gt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtagtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 ccattccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttca a cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctggggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 22 <211> 427 < 212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 22

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile

55 60

- 187 046596

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Arg Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

- 188 046596

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 23 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 23 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctga ggcagaagct ggccaaggac 660

- 189 046596 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcag tgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc cc gccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 24 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 24

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

- 190 046596

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Thr Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

- 191 046596

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu 405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr 420 425 <210> 25 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 25 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta tggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcacc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080

- 192 046596 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc cc gccgagca gcctttgagc 1260 acacctctga gccacagcac c 1281 <210> 26 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 26

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

- 193 046596

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Thr Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

- 194 046596

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr 420 425 <210> 27 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 27 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcacc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ctagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgccca gc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 28 <211> 427 <212> PROTEIN

- 195 046596 <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 28

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

- 196 046596

Ser Asn Asp Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Thr Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 29 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide

- 197 046596 <400> 29 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatcagg tggaagagtg cagagtgaag gg ccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagag cc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga tatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtc gtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcacc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg tc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 30 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 30

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

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

25 30

- 198 046596

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

- 199 046596

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Pro Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 31 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 31 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctggggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360

- 200 046596 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcc cca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tcc accccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcc t tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgccgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 32 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 32

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro

70 75 80

- 201 046596

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

- 202 046596

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 33 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 33 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccttgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780

- 203 046596 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagc gcct tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcag cgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gttacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 34 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 34

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

- 204 046596

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Lys Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Pro Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

- 205 046596

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly

385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Ser Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 35 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 35 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggcgctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaagg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccaggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgc cca tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgccca gc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgccgcaggg ctaccacttc 1140

- 206 046596 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatct ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 36 <21 1> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 36

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

- 207 046596

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Asn Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425

- 208 046596 <210> 37 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 37 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccaac cctgggagga aatcaagacc tcctacgctg gcgtgaacga gaagtacctg 1080 agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 38 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

- 209 046596 <221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 38

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

- 210 046596

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 39 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 39 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60

- 211 046596 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggcca ggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccagg aaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggctct gt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaatt acc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgct g gcgtgaaaga gaagtacctg 1080 agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct acc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 40 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 40

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg

- 212 046596

40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Asp Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

- 213 046596

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 41 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 41 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcgacatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480

- 214 046596 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggct ctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggca attacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210 > 42 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 42

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

- 215 046596

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

- 216 046596

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu Asp Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly

385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 43 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 43 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840

- 217 046596 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140 accgccgata gagga catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 44 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 44

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

- 218 046596

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Gly Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Ser Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly

- 219 046596

385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 45 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 45 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacgg gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccactcc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260

- 220 046596 acacctctga gccacagcac c 1281 <210> 46 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 46

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

- 221 046596

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Arg Thr Pro Leu Ser His Ser Thr 420 425 <210> 47 <211> 1281

- 222 046596 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 47 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgcgc 1260 acacctctga gccacagcac c 1281 <210 > 48 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide

- 223 046596 <400> 48

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Gly Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

- 224 046596

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Gly Thr Pro Leu Ser His Ser Thr 420 425 <210> 49 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 49 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180

- 225 046596 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggt ggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgt gcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacgg gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattc ga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcc t tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggca g cgacgccggc 1200 tggacactgg gctacatgtt gaatctgacc aacatgatcc ccgccgagca gcccctgggc 1260 acacctctga gccacagcac c 1281 <210> 50 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 50

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg

40 45

- 226 046596

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Met Cys Tyr Gly

195 200 205

Lys Asp Gln Ala Leu Arg Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

- 227 046596

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Ser Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Arg Thr Pro Leu Ser His Ser Thr 420 425 <210> 51 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 51 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540

- 228 046596 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttatgtgcta cggaaaggac caggctctga ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct t ccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgtacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt g cgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccactcc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgaga 1260 acacctctga gccacagcac c 1281 < 210> 52 <211> 427 < 212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 52

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Lys Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

- 229 046596

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

- 230 046596

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Asn His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly

385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 53 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 53 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaagga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960

- 231 046596 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140 accgccgata gctgggagca caaccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 12 81 <210> 54 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 54

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

- 232 046596

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Asn Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

- 233 046596

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 55 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 55 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccaac cctgggagga aatcaagacc tcctacgctg gcgtgaacga gaagtacctg 1080 agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281

- 234 046596 <210> 56 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 56

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

- 235 046596

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 57 <211> 1281 <212> DNA <213> Artificial sequence

- 236 046596 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 57 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 58 <211>430 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 58

Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly 1 5 10 15

- 237 046596

Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys 20 25 30

Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu 35 40 45

Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val 50 55 60

Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu 65 70 75 80

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

90 95

Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp

100 105 110

Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp

115 120 125

Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly

130 135 140

Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln 145 150 155 160

Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr

165 170 175

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

180 185 190

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

195 200 205

Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile

210 215 220

Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly

225 230 235 240

Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr

245 250 255

- 238 046596

Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly

260 265 270

Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn

275 280 285

Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu

290 295 300

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

305 310 315 320

Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val

325 330 335

Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys

340 345 350

Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe

355 360 365

Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr

370 375 380

Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser

385 390 395 400

Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile

405 410 415

Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430 <210> 59 <211> 1290 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 59 gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggac 60 gccggctcct cccacacctc cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120 gtgg tgcaccaagt ggaagagtgc agagtgaagg gccccggcat ctccaagttc 180 gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccagagaa 240

- 239 046596 gtgatccctc ggtcccagca ccaggaaacc cctgtctacc tgggcgccac cgccggcatg 300 cggctgctgc ggatggaatc cgaggaactg gccgaccggg tgctggacgt ggtggaacgg 360 tccctgtcca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagag 420 ggcgcctacg gctggatcac catcaactac ctgctgggca agttctccca gaagaatcag 480 gaaaccttcg gcgccctgga cctgggcgga gccagcaccc aagtcacatt cgtgccccag 540 aaccagacca tcgagagccc cgacaacgcc ctgcag ttcc ggctgtacgg caaggactac 600 aacgtgtaca cccacagctt tctgtgctac ggcaaggacc aggccctgtg gcagaagctg 660 gccaaggaca tccaagtggc ctccaacgag atcctgcggg acccctgctt ccaccccggc 720 tacaagaaag tggtcaacgt gtccgacctg tacaagaccc cttgcaccaa gagattcgag 780 atgaccctgc ccttccagca gttcgagatc cagggcatcg acca gcagtgccac 840 cagtccatcc tggaactgtt caacacctcc tactgcccct actcccagtg cgccttcaac 900 ggcatcttcc tgcctccact gcagggcgac ttcggcgcct tctccgcctt ctacttcgtg 960 atgaagttcc tgaacctgac ctccgagaaa gtgtc ccagg aaaaagtgac cgagatgatg 1020 aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080 aagtacctgt ccgagtactg cttctccggc acctacatcc tgtccctgct gctgcagggc 1140 taccacttca ccgccgacag ctgggagcac atccacttca tcggcaagat ccagggatcc 1200 gacgctggct ggaccctggg ctacatgctg aatctgacca acatgatccc cgcc gagcag 1260 cccctgtcca cccctctgtc tcactccacc 1290 <210> 60 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 60

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile

55 60

- 240 046596

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

- 241 046596

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 61 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 61 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccttgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660

- 242 046596 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcag tgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag ga aaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gttacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 62 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 62

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

- 243 046596

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Thr Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

- 244 046596

Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu Asp Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly

385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 63 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 63 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcacc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020

- 245 046596 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140 accgccgata gctgggagga catccacttc atcggca aga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 64 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 64

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

- 246 046596

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

- 247 046596

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr 420 425 <210> 65 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 65 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccttgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgccca gc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gttacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 66 <211> 442

- 248 046596 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 66

Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Thr Ser Ser Thr

5 10 15

Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu Asp 20 25 30

Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu 35 40 45

Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val 50 55 60

Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly 65 70 75 80

Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro Arg 85 90 95

Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met

100 105 110

Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp

115 120 125

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

130 135 140

Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile 145 150 155 160

Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe Gly

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

- 249 046596

Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser

225 230 235 240

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

245 250 255

Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu

260 265 270

Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr

275 280 285

Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys

290 295 300

Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln

305 310 315 320

Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu

325 330 335

Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met

340 345 350

Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala

355 360 365

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

370 375 380

Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp

385 390 395 400

Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp

405 410 415

Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln

420 425 430

Pro Leu Ser Thr Pro Leu Ser His Ser Thr

435 440 <210> 67 <211> 1326 <212> DNA <213> Artificial sequence

- 250 046596 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 67 gcccctacca gcagcagcac caagaaaacc cagctgacca gcagcaccca gaacaaggcc 60 ctgcccgaga acgtgaagta cggcatcgtg ctggatgccg gcagcagcca caccagcctg 120 tacatctaca agtggcctgc cgagaaagaa aacgacaccg gcgtggtgca tcaggtggaa 180 gagtgcagag tgaagggccc tggcatcagc aagttcgtgc agaaagtgaa cgagatcggc 240 atctacctga ccgactgcat ggaacgggcc agggaagtga tccccagaag ccagcaccag 300 gaaacccccg tgtatctggg agccaccgcc ggcatgagac tgctgagaat ggaaagcgag 360 gaactggccg accgggtgct ggacgtggtg gaaagaagcc tgagcaacta cccattcgat 420 tttcaaggcg cca gaatcat caccggccag gaagaaggcg cctacggctg gatcaccatc 480 aactacctgc tgggcaagtt cagccagaag aatcaggaaa ccttcggcgc cctggacctg 540 ggcggagctt ctacccaagt gaccttcgtg ccccagaatc agaccatcga gagccccgac 600 agttccggct gtacggcaag gactacaatg tgtacaccca cagctttctg 660 tgctacggaa aggaccaggc tctgtggcag aagctggcca aggacatcca ggtggccagc 720 aacgagatcc tgcgggaccc ttgcttccac cccggctaca agaaagtcgt gaacgtgtcc 780 gacctgtaca agaccccctg caccaagaga ttcgagatga ccctgccctt ccagcagttc 840 gagatccagg gcatcggcaa ttacc agcag tgccaccaga gcatcctgga actgttcaac 900 accagctact gcccctacag ccagtgcgcc ttcaacggca tcttcctgcc acctctgcag 960 ggggatttcg gcgccttcag cgccttctac ttcgtgatga agttcctgaa cctgaccagc 1020 gagaaggtgt c ccaggaaaa agtgacagag atgatgaaga agttctgcgc ccagccctgg 1080 gaggaaatca agacctccta cgctggcgtg aaagagaagt acctgagcga gtactgcttc 1140 agcggcacct acatcctgag cctgctgctg cagggctacc acttcaccgc cgatagctgg 1200 gagcacatcc acttcatcgg caagattcag ggcagcgacg ccggctggac actgggctac 1260 atgctgaatc tgaccaacat gatccccgcc gagcagcccc t gagcacacc tctgagccac 1320 agcacc 1326 <210> 68 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide

- 251 046596 <400> 68

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

- 252 046596

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu Asp Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly

385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 69 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 69 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180

- 253 046596 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggt ggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgt gcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattc ga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcc t tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtttt gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140 accgccgata gctgggagga catccacttc atcggcaaga ttcag ggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 70 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 70

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg

40 45

- 254 046596

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

- 255 046596

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 71 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 71 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540

- 256 046596 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtttt gcttcagcgg cacctacat c ctgagcctgc tgcagcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1 281 <210> 72 <211>443 < 212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 72

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

5 10 15

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 20 25 30

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 35 40 45

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 50 55 60

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 65 70 75 80

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 85 90 95

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

- 257 046596

100 105 110

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

115 120 125

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

130 135 140

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr 145 150 155 160

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

165 170 175

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

180 185 190

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

195 200 205

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

210 215 220

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala 225 230 235 240

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 245 250 255

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

260 265 270

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

275 280 285

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

290 295 300

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

305 310 315 320

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

325 330 335

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

340 345 350

- 258 046596

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

355 360 365

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

370 375 380

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

385 390 395 400

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly

405 410 415

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

420 425 430

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

435 440 <210> 73 <211> 1329 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 73 gcccctacct cctccagcac caagaaaacc cagctgacct ccagcggcac ccagaacaag 60 gccctgcccg agaacgtgaa gtacggcatc gtgctggacg ccggctcctc ccacacctcc 120 ctgta catct acaagtggcc tgccgagaaa gaaaacgaca ccggcgtggt gcaccaagtg 180 gaagagtgca gagtgaaggg ccccggcatc tccaagttcg tgcagaaagt gaacgagatc 240 ggcatctacc tgaccgactg catggaacgg gccagagaag tgatccctcg gtcccagcac 300 caggaaaccc ctgtctacct gggcgccacc gccggcatgc ggctgctgcg gatggaatcc 360 gaggaactgg ccgaccgggt gctggacgtg gtggaacggt ccctgtccaa ctacccattc 420 gattttcaag ccagaat catcaccggc caggaagagg gcgcctacgg ctggatcacc 480 atcaactacc tgctgggcaa gttctcccag aagaatcagg aaaccttcgg cgccctggac 540 ctgggcggag ccagcaccca agtcacattc gtgccccaga accagaccat cgagagcccc 600 gacaacgccc tgcagtt ccg gctgtacggc aaggactaca acgtgtacac ccacagcttt 660 ctgtgctacg gcaaggacca ggccctgtgg cagaagctgg ccaaggacat ccaagtggcc 720 tccaacgaga tcctgcggga cccctgcttc caccccggct acaagaaagt ggtcaacgtg 780 tccgacctgt acaagacccc ttgcaccaag agattcgaga tgaccctgcc cttccagcag 840

- 259 046596 ttcgagatcc agggcatcgg caactaccag cagtgccacc agtccatcct ggaactgttc 900 aacacctcct actgccccta ctcccagtgc gccttcaacg gcatcttcct gcctccactg 960 cagggcgact tcggcgcctt ctccgccttc tacttcgt ga tgaagttcct gaacctgacc 1020 tccgagaaag tgtcccagga aaaagtgacc gagatgatga agaagttctg cgcccagccc 1080 tgggaggaaa tcaagacctc ctacgctggc gtgaaagaga agtacctgtc cgagtactgc 1140 ttctccggca cctacatcct gt ccctgctg ctgcagggct accacttcac cgccgacagc 1200 tgggagcaca tccacttcat cggcaagatc cagggatccg acgctggctg gaccctgggc 1260 tacatgctga atctgaccaa catgatcccc gccgagcagc ccctgtccac ccctctgtct 1320 cactccacc 1329 <210> 74 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 74

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

- 260 046596

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

- 261 046596

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly

385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 75 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 75 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgccca gc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140

- 262 046596 accgccgata gctggggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 76 <21 1> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 76

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

- 263 046596

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425

- 264 046596 <210> 77 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 77 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccatgga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagttct gcttcagcgg cacctacatc ctgagcctgc tgcagcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 78 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

- 265 046596 <221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 78

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

- 266 046596

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 79 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 79 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60

- 267 046596 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggcca tgga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gcca ggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccttgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggct ctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggca attacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gttacatgct gaatctgacc aa catgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 80 <211>433 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 80

Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val 1 5 10 15

Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr 20 25 30

Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His

- 268 046596

40 45

Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val 50 55 60

Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg 65 70 75 80

Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr 85 90 95

Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu

100 105 110

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

115 120 125

Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly

130 135 140

Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln 145 150 155 160

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

165 170 175

Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn

180 185 190

Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His

195 200 205

Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala 210 215 220

Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe 225 230 235 240

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

245 250 255

Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu

260 265 270

Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu

275 280 285

- 269 046596

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

290 295 300

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

305 310 315 320

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

325 330 335

Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu

340 345 350

Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu

355 360 365

Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr

370 375 380

His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile

385 390 395 400

Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr

405 410 415

Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser

420 425 430

Thr <210> 81 <211> 1299 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 81 gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60 gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120 aacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180 agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240 gccagggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300 gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360

- 270 046596 gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420 caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480 aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctacc ca agtgaccttc 540 gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600 aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660 cagaagctgg ccaaggacat agcaacgaga t cctgcggga cccttgcttc 720 caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ca gcgccttc 960 tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020 gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080 gtgaaagaga agtacctgag cgagtactgc tt cagcggca cctacatcct gagcctgctg 1140 ctgcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200 cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260 gccgagcagc ccctgagcac acctctgagc cacagcacc 1299 <210> 82 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 82

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro

70 75 80

- 271 046596

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Ala Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

- 272 046596

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 83 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 83 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaagc cggcgcctac 420 ggctggatca a cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720

- 273 046596 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gc gccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 84 <211 > 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 84

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

- 274 046596

Ala Arg Ile Ile Thr Gly Gln Glu Ala Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

- 275 046596

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly

385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 85 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 85 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaagc cggcgcctac 420 ggctggatca a cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agctgctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctacttcgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140

- 276 046596 accgccgata gctggggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 86 <21 1> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 86

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Gln Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

- 277 046596

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425

- 278 046596 <210> 87 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 87 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaacagga caccggcgtg 120 gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgccca gc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 88 <211> 427 <212> PROTEIN <213> Artificial sequence

- 279 046596 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 88

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Ala Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys

- 280 046596

225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 89 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 89 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60

- 281 046596 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatcagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggcca ggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccagg aaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcaggcc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggctct gt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaatt acc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aa catgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 90 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 90

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

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

25 30

- 282 046596

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Gln Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

- 283 046596

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 91 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 91 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420

- 284 046596 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtac g gcaaggacta caatgtgtac 600 acccacagct ttctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgcagg tgtccgacct gtacaagacc ccctgca cca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcagggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaa aagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 92 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 92

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro

70 75 80

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

- 285 046596

90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Gln Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

- 286 046596

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 93 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 93 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840

- 287 046596 ctggaactgt tccagaccag ctactgcccc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag ga aaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctggga gca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 94 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 94

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

- 288 046596

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Gln Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

- 289 046596

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly

385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 95 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 95 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960 ctgcagctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgc ccagc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200

- 290 046596 tggacactgg gctacatgct gaatctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 96 <211> 427 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 96

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu

5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

- 291 046596

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

195 200 205

Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr

355 360 365

Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser

370 375 380

Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly 385 390 395 400

Trp Thr Leu Gly Tyr Met Leu Gln Leu Thr Asn Met Ile Pro Ala Glu

405 410 415

Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 97

- 292 046596 <211> 1281 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 97 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcatca gg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggaaaggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaattacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcgcct tctactccgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgccca gc cctgggagga aatcaagacc tcctacgctg gcgtgaaaga gaagtacctg 1080 agcgagtact gcttcagcgg cacctacatc ctgagcctgc tgctgcaggg ctaccacttc 1140 accgccgata gctgggagca catccacttc atcggcaaga ttcagggcag cgacgccggc 1200 tggacactgg gctacatgct gcagctgacc aacatgatcc ccgccgagca gcccctgagc 1260 acacctctga gccacagcac c 1281 <210> 98 <211> 69 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer

- 293 046596 <400> 98 tgccctacga gacaaacaat caggaaacct tcggcgccct ggacctgggc ggagcttcta 60 cccaagtga 69 <210> 99 <211> 431 <212> PROTEIN <213> Homo sapiens <400> 99

Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu Asp 1 5 10 15

Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu 20 25 30

Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val 35 40 45

Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly 50 55 60

Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro Arg 65 70 75 80

Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met 85 90 95

Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp

100 105 110

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

115 120 125

Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile

130 135 140

Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Thr Arg Trp Phe Ser Ile 145 150 155 160

Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr Phe Gly Ala Leu Asp Leu

165 170 175

Gly Gly Ala Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile

180 185 190

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

- 294 046596

195 200 205

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

210 215 220

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

225 230 235 240

Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser

245 250 255

Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro

260 265 270

Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His

275 280 285

Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser Gln

290 295 300

Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly

305 310 315 320

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

325 330 335

Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys

340 345 350

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

355 360 365

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

370 375 380

Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His

385 390 395 400

Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr

405 410 415

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

420 425 430 <210> 100 <211> 1293 <212> DNA

- 295 046596 <213> Homo sapiens <400> 100 cagaacaaag ccctgcccga gaacgtgaag tacggcatcg tgctggatgc cggcagcagc 60 cacaccagcc tgtacatcta caagtggcct gccgagaaag aaaacgatac cggtgtcgtg 120 caccaggtgg a agagtgcag agtgaagggc cctggcatca gcaagttcgt gcagaaagtg 180 aacgagatcg gcatctacct gaccgactgc atggaacggg ccagagaagt gatccccaga 240 agccagcacc aggaaacccc cgtgtacctg ggagccacag ccggcatgag actgctgcgg 300 atggaaagc g aggaactggc cgacagagtg ctggacgtgg tggaaagaag cctgagcaac 360 tacccattcg attttcaagg ggccagaatc atcaccggcc aggaagaggg cgcttacggc 420 tggatcacca tcaactacct gctgggcaag ttcagccaga aaacccggtg gttcagcatc 480 gtgccctacg agacaaacaa tcaggaa acc ttcggagccc tggacctggg cggagcctct 540 acccaagtga ccttcgtgcc ccagaatcag accatcgaga gccccgacaa cgccctgcag 600 ttccggctgt acggcaagga ctacaatgtg tacacccaca gctttctgtg ctacggaaag 660 gaccaggccc tgtggcagaa gctgg ccaag gacatccagg tggccagcaa cgagatcctg 720 cgggaccctt gcttccaccc cggctacaag aaagtcgtga acgtgtccga cctgtacaag 780 accccctgca ccaagagatt cgagatgacc ctgcccttcc agcagttcga gatccaggc 840 atcggcaact accagcagtg ccaccagagc atcctggaac tgttcaacac cagctactgc 900 ccctacagcc agtgcgcctt caacggcatc ttcc tgccac ctctgcaggg ggacttcggc 960 gctttcagcg ccttctactt cgtgatgaag ttcctgaacc tgaccagcga gaaggtgtcc 1020 caggaaaaag tgacagagat gatgaagaag ttctgcgccc agccctggga ggaaatcaag 1080 acctcctacg ctggcgt gaa agagaagtac ctgagcgagt actgcttcag cggtacctac 1140 atcctgagcc tgctgctgca gggctaccac ttcaccgccg atagctggga GCACATCCAC 1200 TTCATCGCA AGATTCAGGGGCGCCCCCCCCCCACACACACACACACACACACTACAT GCTGAATCTG 1260 ACCACACCCCGCGA GCAGCCCCTG AGC 1293 <211> 431 <2 212> protein <22> protein <22> protein <22> protein <22> sapiens <400> 101

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

5 10 15

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

25 30

- 296 046596

Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro 65 70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val

165 170 175

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

180 185 190

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

195 200 205

Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp

210 215 220

Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro 225 230 235 240

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

245 250 255

Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln

260 265 270

Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe

275 280 285

- 297 046596

Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe

290 295 300

Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe

305 310 315 320

Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys

325 330 335

Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile

340 345 350

Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys

355 360 365

Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe

370 375 380

Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly 385 390 395 400

Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met 405 410 415

Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430 <210> 102 <211> 1293 <212> DNA <213> Homo sapiens <400> 102 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtg c accaggtgga agagtgcaga 120 gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa aacccggtgg ttcagcatcg tgccctacga gacaaacaat 480 caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540

- 298 046596 cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600 tacaatgtgt acacccacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660 ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacc cttg cttccacccc 720 ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga ccccctgcac caagagattc 780 gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcagtgc 840 caccagagca tcctggaact gttcaacacc agctactgcc c ctacagcca gtgcgccttc 900 aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960 gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020 atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080 gagaagtacc tgagcgagta ctgcttcagc gg tacctaca tcctgagcct gctgctgcag 1140 ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200 agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatgat ccccgccgag 1260 cagcccctga gcacacctct gtctcacagc acc 1293 <210> 103 <211> 416 <212> PROTEIN <213> Homo sapiens <400> 103

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

5 10 15

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro

70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

- 299 046596

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val

165 170 175

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

180 185 190

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

195 200 205

Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp

210 215 220

Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro

225 230 235 240

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

245 250 255

Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln

260 265 270

Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe

275 280 285

Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe

290 295 300

Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe

305 310 315 320

Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys

325 330 335

Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile

340 345 350

Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys

355 360 365

- 300 046596

Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe 370 375 380

Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly 385 390 395 400

Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met

405 410 415 <210> 104 <211> 1248 <212> DNA <213> Homo sapiens <400> 104 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtg c accaggtgga agagtgcaga 120 gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa aacccggtgg ttcagcatcg tgccctacga gacaaacaat 480 caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540 cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccgg ctgta cggcaaggac 600 tacaatgtgt acacccacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660 ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacccttg cttccacccc 720 ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga ccccctgcac caagagattc 780 gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagca gtgc 840 caccagagca tcctggaact gttcaacacc agctactgcc cctacagcca gtgcgccttc 900 aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960 gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaa aaagt gacagagatg 1020 atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080 gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140 ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200 agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248

- 301 046596 <210> 105 <211> 404 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 105

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

5 10 15

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro 65 70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro

165 170 175

Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr

180 185 190

Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys

195 200 205

- 302 046596

Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro

210 215 220

Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr 225 230 235 240

Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln

245 250 255

Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile

260 265 270

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

275 280 285

Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser

290 295 300

Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val 305 310 315 320

Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro

325 330 335

Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu

340 345 350

Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln

355 360 365

Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly

370 375 380

Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn

385 390 395 400

Leu Thr Asn Met <210> 106 <211> 1212 <212> DNA <213> Artificial Sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 106

- 303 046596 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120 gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acc cattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa aaatcaggaa accttcggag ccctggacct gggcggagcc 480 tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540 cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctt tct gtgctacgga 600 aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 660 ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 720 aagaccccct gcaccaagag attcgagatg accctgccct tccag cagtt cgagatccag 780 ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 840 tgcccctaca gccagtgcgc cttcaacggc atcttcctgc cacctctgca gggggacttc 900 ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960 tcccaggaaa aagtgacaga gatgatgaag aagttctgc g cccagccctg ggaggaaatc 1020 aagacctcct acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggtacc 1080 tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1140 cacttcatcg gcaagattca gggcagcgac g ccggctgga cactgggcta catgctgaat 1200 ctgaccaaca tg 1212 <210> 107 <211> 416 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 107

Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser 1 5 10 15

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Ala Arg Val Lys Gly Pro Gly Ile Ser Lys

- 304 046596

40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Ala Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro 65 70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val

165 170 175

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

180 185 190

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

195 200 205

Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp

210 215 220

Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro

225 230 235 240

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

245 250 255

Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln

260 265 270

Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe

275 280 285

- 305 046596

Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe

290 295 300

Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe

305 310 315 320

Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys

325 330 335

Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile

340 345 350

Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys

355 360 365

Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe

370 375 380

Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly 385 390 395 400

Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met 405 410 415 <210> 108 <211> 1248 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 108 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agaggccaga 120 agggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgacgcca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa a acccggtgg ttcagcatcg tgccctacga gacaaacaat 480 caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540 cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600

- 306 046596 tacaatgtgt acacccacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660 ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacccttg cttccacccc 720 ggctacaaga aagtcgtgaa cgtgtccgac ctgtaca aga ccccctgcac caagagattc 780 gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcagtgc 840 caccagagca tcctggaact gttcaacacc agctactgcc cctacagcca gtgcgccttc 900 aacggcatct tcctgccacc tctgcagggg gacttcggc g ctttcagcgc cttctacttc 960 gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020 atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080 gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140 ggctaccact tcaccgccga tagctgggag cacatccact tcatc ggcaa gattcagggc 1200 agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248 <210> 109 <211> 416 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 109

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

5 10 15

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro 65 70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

- 307 046596

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val

165 170 175

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

180 185 190

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

195 200 205

Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp

210 215 220

Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Ala Phe His Pro

225 230 235 240

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

245 250 255

Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln

260 265 270

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

275 280 285

Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe

290 295 300

Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe

305 310 315 320

Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys

325 330 335

Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile

340 345 350

Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys

355 360 365

- 308 046596

Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe

370 375 380

Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly

385 390 395 400

Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met

405 410 415 <210>110 <211> 1248 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 110 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120 g tgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa a acccggtgg ttcagcatcg tgccctacga gacaaacaat 480 caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540 cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600 tacaatgtgt acacc cacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660 ctggccaagg acatccaggt ggccagcaac gagatcctgc gggaccctgc cttccacccc 720 ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga ccccctgcac caagagattc 780 gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcaggcc 840 caccagagca tcctggaact gttca acacc agctactgcc cctacagcca gtgcgccttc 900 aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960 gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020 atgaagaagt tctg cgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080 gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140

- 309 046596 ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200 agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248 <210>111 <211> 416 <212> PROTEIN <213> Artificial sequence <220 >

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400>111

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

5 10 15

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro 65 70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val

165 170 175

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

180 185 190

- 310 046596

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

195 200 205

Leu Ala Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp

210 215 220

Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro

225 230 235 240

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

245 250 255

Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln

260 265 270

Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe

275 280 285

Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe

290 295 300

Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe

305 310 315 320

Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys

325 330 335

Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile

340 345 350

Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys

355 360 365

Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe

370 375 380

Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly 385 390 395 400

Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met 405 410 415 <210>112 <211> 1248 <212> DNA <213> Artificial sequence

- 311 046596 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 112 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120 g tgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa a acccggtgg ttcagcatcg tgccctacga gacaaacaat 480 caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540 cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600 tacaatgtgt acacc cacag ctttctggcc tacggaaagg accaggccct gtggcagaag 660 ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacccttg cttccacccc 720 ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga cccccgccac caagagattc 780 gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcagtgc 840 caccagagca tcctggaact gtt caacacc agctactgcc cctacagcca gtgcgccttc 900 aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960 gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020 atgaagaagt tct gcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080 gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140 ggctaccact tcaccgccga tagctgggag cacatccact tcatcggcaa gattcagggc 1200 agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248 <210> 113 <211> 416 <212> PROTEIN <213> artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400>113

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

5 10 15

- 312 046596

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro 65 70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val

165 170 175

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

180 185 190

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

195 200 205

Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp

210 215 220

Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro

225 230 235 240

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

245 250 255

Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln

260 265 270

- 313 046596

Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe

275 280 285

Asn Thr Ser Tyr Ala Pro Tyr Ser Gln Ala Ala Phe Asn Gly Ile Phe

290 295 300

Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe

305 310 315 320

Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys

325 330 335

Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile

340 345 350

Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys

355 360 365

Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe

370 375 380

Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly 385 390 395 400

Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met 405 410 415 <210>114 <211> 1248 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 114 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120 g tgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagaggc gcttacggct ggatcaccat caactacctg 420

- 314 046596 ctgggcaagt tcagccagaa aacccggtgg ttcagcatcg tgccctacga gacaaacaat 480 caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540 cagaatcaga ccatcgagag ccccgacaac gccctgcag t tccggctgta cggcaaggac 600 tacaatgtgt acacccacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660 ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacccttg cttccacccc 720 ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga ccccctgcac caagagattc 780 gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcagtgc 840 caccagagca tcctggaact gttcaacacc agctacgccc cctacagcca ggccgccttc 900 aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960 gtgatgaagt tcctgaacct gaccagcgag aaggtgtc cc aggaaaaagt gacagagatg 1020 atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080 gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140 ggctaccact tcaccgccga tagctggga g cacatccact tcatcggcaa gattcagggc 1200 agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248 <210> 115 <211> 416 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 115

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

5 10 15

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro 65 70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

- 315 046596

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Gln Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val

165 170 175

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

180 185 190

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

195 200 205

Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp

210 215 220

Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro

225 230 235 240

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

245 250 255

Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln

260 265 270

Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe

275 280 285

Asn Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe

290 295 300

Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe

305 310 315 320

Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys

325 330 335

Val Thr Glu Met Met Lys Lys Phe Ala Ala Gln Pro Trp Glu Glu Ile

- 316 046596

340 345 350

Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Ala

355 360 365

Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe

370 375 380

Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly

385 390 395 400

Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met

405 410 415 <210>116 <211> 1248 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 116 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120 g tgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa a acccggtgg ttcagcatcg tgccctacga gacaaacaat 480 caggaaacct tcggagccct ggacctgggc ggagcctcta cccaagtgac cttcgtgccc 540 cagaatcaga ccatcgagag ccccgacaac gccctgcagt tccggctgta cggcaaggac 600 tacaatgtgt acacc cacag ctttctgtgc tacggaaagg accaggccct gtggcagaag 660 ctggccaagg acatccaggt ggccagcaac gagatcctgc gggacccttg cttccacccc 720 ggctacaaga aagtcgtgaa cgtgtccgac ctgtacaaga ccccctgcac caagagattc 780 gagatgaccc tgcccttcca gcagttcgag atccagggca tcggcaacta ccagcagtgc 840 caccagagca tcctggaact gt tcaacacc agctactgcc cctacagcca gtgcgccttc 900 aacggcatct tcctgccacc tctgcagggg gacttcggcg ctttcagcgc cttctacttc 960 gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020

- 317 046596 atgaagaagt tcgccgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080 gagaagtacc tgagcgagta cgccttcagc ggtacctaca tcctgagcct gctgctgcag 1140 ggctaccact tcaccgccga tagctgggag cacatccact tcat cggcaa gattcagggc 1200 agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatg 1248 <210> 117 <211> 404 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 117

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

5 10 15

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Ala Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Ala Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro 65 70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro

165 170 175

- 318 046596

Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr

180 185 190

Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys

195 200 205

Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro

210 215 220

Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr 225 230 235 240

Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln

245 250 255

Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile

260 265 270

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

275 280 285

Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser

290 295 300

Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val 305 310 315 320

Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro

325 330 335

Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu

340 345 350

Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln

355 360 365

Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly

370 375 380

Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn

385 390 395 400

Leu Thr Asn Met

- 319 046596 <210>118 <211> 1212 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 118 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agaggccaga 120 agggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgacgcca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa a aatcaggaa accttcggag ccctggacct gggcggagcc 480 tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540 cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 600 aaggaccagg ccctgtgg ca gaagctggcc aaggacatcc aggtggccag caacgagatc 660 ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 720 aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 780 ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 840 tgcccctaca gccagtgcgc cttcaac ggc atcttcctgc cacctctgca gggggacttc 900 ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960 tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1020 aagacctcc t acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggtacc 1080 tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1140 cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1200 ctgaccaaca tg 1212 <210> 119 <211> 404 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide

- 320 046596 <400>119

Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser 1 5 10 15

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro 65 70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro

165 170 175

Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr

180 185 190

Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys

195 200 205

Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro

210 215 220

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

225 230 235 240

Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln

- 321 046596

245 250 255

Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Ala His Gln Ser Ile

260 265 270

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

275 280 285

Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser

290 295 300

Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val 305 310 315 320

Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro

325 330 335

Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu

340 345 350

Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln

355 360 365

Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly

370 375 380

Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn

385 390 395 400

Leu Thr Asn Met <210> 120 <211> 1212 <212> DNA <213> Artificial Sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 120 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120 g tgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300

- 322 046596 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa aaatcaggaa accttcggag acct gggcggagcc 480 tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540 cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 600 aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggcca g caacgagatc 660 ctgcgggacc ctgccttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 720 aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 780 ggcatcggca actaccagca ggcccaccag agcatcctgg aactgttcaa caccagctac 840 tgcccctaca gccagtgcgc cttcaacggc atcttcctgc cacctctgca gggggacttc 900 ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960 tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1020 aagacctcct acgctggcgt gaaagagaag t acctgagcg agtactgctt cagcggtacc 1080 tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1140 cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1200 ctgaccaaca tg 1212 <210> 121 <211> 404 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 121

Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser 1 5 10 15

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro

70 75 80

- 323 046596

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro

165 170 175

Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr

180 185 190

Thr His Ser Phe Leu Ala Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys

195 200 205

Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro

210 215 220

Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr 225 230 235 240

Lys Thr Pro Ala Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln

245 250 255

Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile

260 265 270

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

275 280 285

Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser

290 295 300

Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val 305 310 315 320

- 324 046596

Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro

325 330 335

Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu

340 345 350

Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln

355 360 365

Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly

370 375 380

Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn

385 390 395 400

Leu Thr Asn Met <210> 122 <211> 1212 <212> DNA <213> Artificial Sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 122 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120 g tgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa a aatcaggaa accttcggag ccctggacct gggcggagcc 480 tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540 cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct ggcctacgga 600 aaggaccagg ccctgtgg ca gaagctggcc aaggacatcc aggtggccag caacgagatc 660 ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 720 aagacccccg ccaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 780 ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 840

- 325 046596 tgcccctaca gccagtgcgc cttcaacggc atcttcctgc cacctctgca gggggacttc 900 ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960 tcccaggaaa aagtgacaga gatgatga ag aagttctgcg cccagccctg ggaggaaatc 1020 aagacctcct acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggtacc 1080 tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1140 cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1200 ctgaccaaca tg 1212 <210 > 123 <211> 404 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 123

Asn Val Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser 1 5 10 15

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro 65 70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

- 326 046596

145 150 155 160

Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro

165 170 175

Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr

180 185 190

Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys

195 200 205

Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro

210 215 220

Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr 225 230 235 240

Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln

245 250 255

Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile

260 265 270

Leu Glu Leu Phe Asn Thr Ser Tyr Ala Pro Tyr Ser Gln Ala Ala Phe

275 280 285

Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser

290 295 300

Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val 305 310 315 320

Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro

325 330 335

Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu

340 345 350

Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln

355 360 365

Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly

370 375 380

Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn

385 390 395 400

- 327 046596

Leu Thr Asn Met <210> 124 <211> 1212 <212> DNA <213> Artificial Sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 124 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120 g tgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaagcga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa a aatcaggaa accttcggag ccctggacct gggcggagcc 480 tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540 cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 600 aaggaccagg ccctgtgg ca gaagctggcc aaggacatcc aggtggccag caacgagatc 660 ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 720 aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 780 ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 840 gccccctaca gccaggccgc cttcaacggc atcttcctgc cacctctgca gggggacttc 900 ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960 tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1020 aagacctcct ac gctggcgt gaaagagaag tacctgagcg agtactgctt cagcggtacc 1080 tacatcctga gcctgctgct gcagggctac cacttcaccg ccgatagctg ggagcacatc 1140 cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1200 ctgaccaaca tg 1212 <210> 125 <211> 404 <212> PROTEIN <213> Artificial sequence

- 328 046596 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 125

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

5 10 15

Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val 20 25 30

Val His Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys 35 40 45

Phe Val Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met 50 55 60

Glu Arg Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro 65 70 75 80

Val Tyr Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser 85 90 95

Glu Glu Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser

100 105 110

Asn Tyr Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu

115 120 125

Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe

130 135 140

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

145 150 155 160

Ser Thr Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro

165 170 175

Asp Asn Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr

180 185 190

Thr His Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys

195 200 205

Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro

210 215 220

- 329 046596

Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr 225 230 235 240

Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln

245 250 255

Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile

260 265 270

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

275 280 285

Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser

290 295 300

Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val 305 310 315 320

Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe Ala Ala Gln Pro

325 330 335

Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu

340 345 350

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

355 360 365

Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly

370 375 380

Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn

385 390 395 400

Leu Thr Asn Met <210> 126 <211> 1212 <212> DNA <213> Artificial Sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 126 aacgtgaagt acggcatcgt gctggatgcc ggcagcagcc acaccagcct gtacatctac 60 aagtggcctg ccgagaaaga aaacgatacc ggtgtcgtgc accaggtgga agagtgcaga 120

- 330 046596 gtgaagggcc ctggcatcag caagttcgtg cagaaagtga acgagatcgg catctacctg 180 accgactgca tggaacgggc cagagaagtg atccccagaa gccagcacca ggaaaccccc 240 gtgtacctgg gagccacagc cggcatgaga ctgctgcgga tggaaag cga ggaactggcc 300 gacagagtgc tggacgtggt ggaaagaagc ctgagcaact acccattcga ttttcaaggg 360 gccagaatca tcaccggcca ggaagagggc gcttacggct ggatcaccat caactacctg 420 ctgggcaagt tcagccagaa aaatcaggaa ccctggacct gggcggagcc 480 tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 540 cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 600 aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 660 ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaac gtgtc cgacctgtac 720 aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 780 ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 840 tgcccctaca gccagtgcgc cttcaacggc atcttcctgc cacc tctgca gggggacttc 900 ggcgctttca gcgccttcta cttcgtgatg aagttcctga acctgaccag cgagaaggtg 960 tcccaggaaa aagtgacaga gatgatgaag aagttcgccg cccagccctg ggaggaaatc 1020 aagacctcct acgctggcgt gaaagagaag tacctgagcg agtacgcctt cagcggtacc 1080 tacatcctga gcctgctgct gcagggctac cacttcaccg ctg ggagcacatc 1140 cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1200 ctgaccaaca tg 1212 <210> 127 <211> 431 <212> PROTEIN <213> Artificial sequence < 220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 127

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile

- 331 046596

55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Thr Arg Trp Phe Ser 145 150 155 160

Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr Phe Gly Ala Leu Asp

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile 225 230 235 240

Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val

245 250 255

Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu 260 265 270

Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys

275 280 285

His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Phe Asn Gly Ile Phe

290 295 300

- 332 046596

Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe 305 310 315 320

Val Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys

325 330 335

Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile

340 345 350

Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys

355 360 365

Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe

370 375 380

Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly 385 390 395 400

Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met 405 410 415

Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430 <210> 128 <211> 1293 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 128 acacagaaca aagccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga taccggtgtc 120 gtgca ccagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccagaga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtac ctgggagcca cagccggcat gagactgctg 300 cggatggaaa gcgaggaact ggccgacaga gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggggccaga atcatcaccg gccaggaaga gggcgcttac 420 ggctggatca ccatcaacta cct gctgggc aagttcagcc agaaaacccg gtggttcagc 480 atcgtgccct acgagacaaa caatcaggaa accttcggag ccctggacct gggcggagcc 540 tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 600

- 333 046596 cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 660 aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 720 ctgcgggacc cttgcttcca ccccggctac aagaaagtcg t gaacgtgtc cgacctgtac 780 aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 840 ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagcttc 900 aacggcatct tcctgccacc tctgcagggg gacttcggcg ctt tcagcgc cttctacttc 960 gtgatgaagt tcctgaacct gaccagcgag aaggtgtccc aggaaaaagt gacagagatg 1020 atgaagaagt tctgcgccca gccctgggag gaaatcaaga cctcctacgc tggcgtgaaa 1080 gagaagtacc tgagcgagta ctgcttcagc ggtacctaca tcctgagcct gctgctgcag 1140 ggctaccact tcaccgccga tagctgggag cacatccact tcatc ggcaa gattcagggc 1200 agcgacgccg gctggacact gggctacatg ctgaatctga ccaacatgat ccccgccgag 1260 cagcccctga gcacacctct gtctcacagc acc 1293 <210> 129 <211> 439 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 129

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

- 334 046596

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Thr Arg Trp Phe Ser 145 150 155 160

Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr Phe Gly Ala Leu Asp

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile 225 230 235 240

Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val

245 250 255

Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu 260 265 270

Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys

275 280 285

His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Ala Pro Tyr Ser

290 295 300

Gln Ala Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe

305 310 315 320

Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu Asn Leu Thr

325 330 335

Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe

340 345 350

- 335 046596

Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys

355 360 365

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

370 375 380

Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile

385 390 395 400

His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly

405 410 415

Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln Pro Leu Ser

420 425 430

Thr Pro Leu Ser His Ser Thr

435 <210> 130 <211> 1317 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 130 acacagaaca aagccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga taccggtgtc 120 gtgca ccagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccagaga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtac ctgggagcca cagccggcat gagactgctg 300 cggatggaaa gcgaggaact ggccgacaga gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggggccaga atcatcaccg gccaggaaga gggcgcttac 420 ggctggatca ccatcaacta cct gctgggc aagttcagcc agaaaacccg gtggttcagc 480 atcgtgccct acgagacaaa caatcaggaa accttcggag ccctggacct gggcggagcc 540 tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 600 cagttccggc tgtac ggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 660 aaggaccagg ccctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 720 ctgcgggacc cttgcttcca ccccggctac aagaaagtcg tgaacgtgtc cgacctgtac 780 aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 840

- 336 046596 ggcatcggca actaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 900 gccccctaca gccaggccgc cttcaacggc atcttcctgc cacctctgca gggggacttc 960 ggcgctttca gcgccttcta cttcgtgatg aagttcct ga acctgaccag cgagaaggtg 1020 tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1080 aagacctcct acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggtacc 1140 tacatcctga gcctgctgct gcagg gctac cacttcaccg ccgatagctg ggagcacatc 1200 cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1260 ctgaccaaca tgatccccgc cgagcagccc ctgagcacac ctctgtctca cagcacc 1317 <210> 131 <211> 16 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 131

Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Thr Ser Ser Gly 1 5 10 15 <210> 132 <211> 48 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic oligonucleotide <400> 132 gcccccacca gcagcagcac caagaagacc cagctgacca gcagcggc 48 <210> 133 <211> 15 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 133

Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Thr Ser Ser 1 5 10 15 <210> 134 <211> 45 <212> DNA <213> Artificial sequence

- 337 046596 <220>

<221> source <223> /note=Description of artificial sequence: Synthetic oligonucleotide <400> 134 gcccctacca gcagcagcac caagaaaacc cagctgacca gcagc 45 <210> 135 <211>6 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 135

Ala Pro Thr Ser Ser Ser 1 5 <210> 136 <211> 18 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic oligonucleotide <400> 136 gcccctacca gcagcagc 18 <210> 137 <211> 3 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 137

Ala Pro Thr 1 <210> 138 <211>9 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic oligonucleotide <400> 138 gcccctacc 9

- 338 046596 <210> 139 <211>9 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 139

Ala Pro Thr Ser Ser Ser Thr Lys Lys 1 5 <210> 140 <211> 27 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic oligonucleotide <400> 140 gcccctacca gcagcagcac caagaaa 27 <210> 141 <211> 12 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 141

Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu 1 5 10 <210> 142 <211> 36 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic oligonucleotide <400> 142 gcccctacca gcagcagcac caagaaaacc cagctg 36 <210> 143 <211> 9 <212> PROTEIN <213> Artificial sequence <220>

<221> source

- 339 046596 <223> /note=Description of artificial sequence: synthetic peptide <400> 143

Ser Ser Ser Thr Lys Lys Thr Gln Leu 1 5 <210> 144 <211> 27 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic oligonucleotide <400> 144 agcagcagca ccaagaaaac ccagctg 27 <210> 145 <211> 426 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 145

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro 65 70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

- 340 046596

Ala Arg Ile Ile Thr Gly Gln Asp Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe 145 150 155 160

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

165 170 175

Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg Leu

180 185 190

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

195 200 205

Arg Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala

210 215 220

Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys 225 230 235 240

Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe

245 250 255

Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn

260 265 270

Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr

275 280 285

Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu

290 295 300

Gln Gly Asp Phe Gly Ala Phe Ser Asn Phe Tyr Tyr Val Met Lys Phe

305 310 315 320

Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met

325 330 335

Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr

340 345 350

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

355 360 365

Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp

370 375 380

- 341 046596

Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp

385 390 395 400

Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln

405 410 415

Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 <210> 146 <211> 1278 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 146 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcat cagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccagaga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggacga gggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaatca ggaaaccttc 480 ggcgccctgg acctgggcgg agcttctacc caagtgacct tcgtgcccca gaatcagacc 540 atcgagagcc ccgacaacgc cctgcagttc cggctgtacg gcaaggacta caatgtgtac 600 acccacagct tctgtgcta cggccgggac caggctctgt ggcagaagct ggccaaggac 660 atccaggtgg ccagcaacga gatcctgcgg gacccttgct tccaccccgg ctacaagaaa 720 gtcgtgaacg tgtccgacct gtacaagacc ccctgcacca agagattcga gatgaccctg 780 cccttccagc agttcgagat ccagggcatc ggcaactacc agcagtgcca ccagagcatc 840 ctggaactgt tcaacaccag ctactgcc cc tacagccagt gcgccttcaa cggcatcttc 900 ctgccacctc tgcaggggga tttcggcgcc ttcagcaact tctactacgt gatgaagttc 960 ctgaacctga ccagcgagaa ggtgtcccag gaaaaagtga cagagatgat gaagaagttc 1020 tgcgcccagc cctgggagga aatcaagacc tcttacgccg gacaggaacg gtggctgcgg 1080 gactactgtt tcagcggcac ctacatcctg tccctgctgc tgcagggcta ccacttcacc 1140

- 342 046596 gccgatagct gggagcacat ccacttcatc ggcaagattc agggcagcga cgccggctgg 1200 acactgggct acatgctgaa tctgaccaac atgatccccg ccgagcagcc cctgagcaca 1260 cctctgtctc acagcacc 1278 <210> 147 <211>5 37 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 147

Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 1 5 10 15

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 20 25 30

Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 35 40 45

Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 50 55 60

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 65 70 75 80

His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 85 90 95

Val Thr Lys Ser Phe Asn Arg Gly Glu Gly Gly Gly Gly Ser Thr Gln

100 105 110

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

115 120 125

Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu Lys

130 135 140

Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val Lys 145 150 155 160

Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly Ile

165 170 175

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

- 343 046596

180 185 190

Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met Arg

195 200 205

Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp Val

210 215 220

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

225 230 235 240

Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile Asn

245 250 255

Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe Gly Ala

260 265 270

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

275 280 285

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

290 295 300

Lys Asp Tyr Asn Val Tyr Thr His Ser Phe Leu Cys Tyr Gly Lys Asp 305 310 315 320

Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser Asn

325 330 335

Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val

340 345 350

Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met

355 360 365

Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln

370 375 380

Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro

385 390 395 400

Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly

405 410 415

Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu Asn

420 425 430

- 344 046596

Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met Lys

435 440 445

Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly

450 455 460

Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly Thr Tyr Ile

465 470 475 480

Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp Glu

485 490 495

His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr

500 505 510

Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln Pro

515 520 525

Leu Ser Thr Pro Leu Ser His Ser Thr

530 535 <210> 148 <211> 1611 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 148 acggtggccg ctcccagcgt gttcatettc ccccccagcg acgagcagct gaagagcggc 60 accgccagcg tggtgtgcct gctgaacaac ttctaccccc gggaggccaa ggtgcagtgg 1 20 aaggtggaca acgccctgca gagcggcaac agccaggaaa gcgtcaccga gcaggacagc 180 aaggactcca cctacagcct gagcagcacc ctgaccctga gcaaggccga ctacgagaag 240 cacaaggtgt acgcctgcga ggtgacccac cagggcctgt ccagccccgt gaccaagagc 300 ttcaaccggg gcgagggagg cggaggatct acccagaaca aggccctgcc cgagaacgtg 360 aagtacggca tcgtgctgga tgccggcagc agccacacca gcctgtacat ctacaagtgg 420 cctgccgaga aagaaa acga caccggcgtg gtgcatcagg tggaagagtg cagagtgaag 480 ggccctggca tcagcaagtt cgtgcagaaa gtgaacgaga tcggcatcta cctgaccgac 540 tgcatggaac gggccaggga agtgatcccc agaagccagc accaggaaac ccccgtgtat 600 ctgggagcca ccgccggcat gagactgctg agaatggaaa gcgaggaact ggccgaccgg 660 gtgctggacg tggtggaaag aagcctgagc aactacccat tcgattttca aggcgccaga 720

- 345 046596 atcatcaccg gccaggaaga aggcgcctac ggctggatca ccatcaacta cctgctgggc 780 aagttcagcc agaagaatca ggaaaccttc ggcgccctgg acctgggcgg agcttctacc 840 caagtgacct tcgtgcccca gaatcagacc atcgagagcc ccgaca acgc cctgcagttc 900 cggctgtacg gcaaggacta caatgtgtac acccacagct ttctgtgcta cggaaaggac 960 caggctctgt ggcagaagct ggccaaggac atccaggtgg ccagcaacga gatcctgcgg 1020 gacccttgct tccaccccgg ctacaagaaa gtcgtgaac g tgtccgacct gtacaagacc 1080 ccctgcacca agagattcga gatgaccctg cccttccagc agttcgagat ccagggcatc 1140 ggcaattacc agcagtgcca ccagagcatc ctggaactgt tcaacaccag ctactgcccc 1200 tacagccagt gcgccttcaa cggcatcttc ctgccacctc tgcaggggga tttcggcgcc 1260 ttcagcgcct tctacttcgt gatgaagttc ctga acctga ccagcgagaa ggtgtcccag 1320 gaaaaagtga cagagatgat gaagaagttc tgcgcccagc cctgggagga aatcaagacc 1380 tcctacgctg gcgtgaaaga gaagtacctg agcgagtact gcttcagcgg cacctacatc 1440 ctgagcctgc tgct gcaggg ctaccacttc accgccgata gctgggagca catccacttc 1500 atcggcaaga ttcagggcag cgacgccggc tggacactgg gctacatgct gaatctgacc 1560 aacatgatcc ccgccgagca gcccctgagc acacctctga gccacagcac c 1611 <210> 149 <211> 508 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 149

Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu 1 5 10 15

Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp 20 25 30

Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys 35 40 45

Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu

55 60

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

70 75 80

- 346 046596

Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val 85 90 95

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

100 105 110

Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys

115 120 125

Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu

130 135 140

Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile 145 150 155 160

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

165 170 175

Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val

180 185 190

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

195 200 205

Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile

210 215 220

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

225 230 235 240

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

245 250 255

Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn Ala Leu Gln Phe Arg

260 265 270

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

275 280 285

Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val

290 295 300

Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys 305 310 315 320

Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg

325 330 335

- 347 046596

Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly

340 345 350

Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser

355 360 365

Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro

370 375 380

Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys

385 390 395 400

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

405 410 415

Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser

420 425 430

Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe Ser Gly

435 440 445

Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp

450 455 460

Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala 465 470 475 480

Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala

485 490 495

Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

500 505 <210> 150 <211> 1524 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 150 atgcaaatct tcgtgaagac cctgactggt aagaccatca ccctcgaggt ggagcccagt 60 gacaccatcg agaatgtcaa ggcaaagatc caagataagg aaggcatccc tcctgatcag 120 ttga tctttgctgg gaaacagctg gaagatggac gcaccctgtc tgactacaac 180

- 348 046596 atccagaaag agtccactct gcacttggtc ctgcgcttga gggggggtgg aggcggagga 240 tctacccaga acaaggccct gcccgagaac gtgaagtacg gcatcgtgct ggatgccggc 300 agcagccaca ccagcctgta catctacaag tggcctgccg aga aagaaaa cgacaccggc 360 gtggtgcatc aggtggaaga gtgcagagtg aagggccctg gcatcagcaa gttcgtgcag 420 aaagtgaacg agatcggcat ctacctgacc gactgcatgg aacgggccag ggaagtgatc 480 cccagaagcc agcaccagga aacccccgtg tatctgg gag ccaccgccgg catgagactg 540 ctgagaatgg aaagcgagga actggccgac cgggtgctgg acgtggtgga aagaagcctg 600 agcaactacc cattcgattt tcaaggcgcc agaatcatca ccggccagga agaaggcgcc 660 tacggctgga tcaccatcaa ctacctgctg ggcaagttca gccagaagaa tcaggaaacc 720 ttcggcgccc tggacctggg cggagcttct acccaagtga ccttcgtg cc ccagaatcag 780 accatcgaga gccccgacaa cgccctgcag ttccggctgt acggcaagga ctacaatgtg 840 tacacccaca gctttctgtg ctacggaaag gaccaggctc tgtggcagaa gctggccaag 900 gacatccagg tggccagcaa cgagatcctg cgggaccctt gcttccaccc cggctacaag 960 aaagtcgtga acgtgtccga cctgtacaag accccctgca ccaagagatt cgagatgacc 1020 ctgcccttcc agcagttcga gatccagggc atcggcaatt accagcagtg ccaccagagc 1080 atcctggaac tgttcaacac cagctactgc ccctacagcc agtgcgcctt caacggcatc 1140 ttcctgccac ctctgcaggg ggatttcggc gccttcagcg c cttctactt cgtgatgaag 1200 ttcctgaacc tgaccagcga gaaggtgtcc caggaaaaag tgacagagat gatgaagaag 1260 ttctgcgccc agccctggga ggaaatcaag acctcctacg ctggcgtgaa agagaagtac 1320 ctgagcgagt actgcttcag cggcacc tac atcctgagcc tgctgctgca gggctaccac 1380 ttcaccgccg atagctggga gcacatccac ttcatcggca agattcaggg cagcgacgcc 1440 ggctggacac tgggctacat gctgaatctg accaacatga tccccgccga gcagcccctg 1500 agcacacctc tgagccacag cacc 1524 <210> 151 <211> 618 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 151

Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu 1 5 10 15

Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln

- 349 046596

25 30

Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu 35 40 45

Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys 50 55 60

Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu 65 70 75 80

Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro 85 90 95

Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu

100 105 110

Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His

115 120 125

Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg

130 135 140

Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg 145 150 155 160

Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala

165 170 175

Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg Gly Gly Gly Gly Ser Thr

180 185 190

Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu Asp

195 200 205

Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu

210 215 220

Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val 225 230 235 240

Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly

245 250 255

Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro Arg

260 265 270

- 350 046596

Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met 275 280 285

Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp

290 295 300

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

305 310 315 320

Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile

325 330 335

Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe Gly

340 345 350

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

355 360 365

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

370 375 380

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

385 390 395 400

Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser

405 410 415

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

420 425 430

Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu

435 440 445

Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr

450 455 460

Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys

465 470 475 480

Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln

485 490 495

Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu

500 505 510

Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met

- 351 046596

515 520 525

Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala

530 535 540

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

545 550 555 560

Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp

565 570 575

Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp

580 585 590

Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln

595 600 605

Pro Leu Ser Thr Pro Leu Ser His Ser Thr

610 615 <210> 152 <211> 1854 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 152 gacgcccaca agagcgaggt ggcccaccgg ttcaaggacc tgggcgagga aaacttcaag 60 gccctggtgc tgatcgcctt cgcccagtac ctgcagcaga gccccttcga agatcacgta 1 20 aagttagtca acgaggttac ggaattcgca aagacatgcg ttgctgacga atccgctgag 180 aattgtgaca agagtttgca cactttattc ggagataagt tgtgtactgt agctactttg 240 agagagactt acggtgaaat ggctgactgc tgtgcaaaac aggaaccaga acgtaacgaa 300 tgtttccttc agcataagga tgataaccct aaccttccaa ggcttgttag gccagaagtc 360 gacgtgatgt gcaccgcctt ccatgataat gaagagactt ttcttaaaaa gtacctatac 420 gagattgcaa ggcgtcatcc atatttttac gccccagagc tgttgttttt cgcaaagaga 480 tacaaagctg catttactga gtgttgccaa gctgccgaca aggccgcttg tttctacca 540 aagttggacg aattgagagg aggcggagga tctacccaga acaaggccct gcccgagaac 600 gt gaagtacg gcatcgtgct ggatgccggc agcagccaca ccagcctgta catctacaag 660 tggcctgccg agaaagaaaa cgacaccggc gtggtgcatc aggtggaaga gtgcagagtg 720 aagggccctg gcatcagcaa gttcgtgcag aaagtgaacg agatcggcat ctacctgacc 780

- 352 046596 gactgcatgg aacgggccag ggaagtgatc cccagaagcc agcaccagga aacccccgtg 840 tatctgggag ccaccgccgg catgagactg ctgagaatgg aaagcgagga actggccgac 900 cgggtgctgg acgtggtgga aagaagcctg agcaactacc cattcgattt t caaggcgcc 960 agaatcatca ccggccagga agaaggcgcc tacggctgga tcaccatcaa ctacctgctg 1020 ggcaagttca gccagaagaa tcaggaaacc ttcggcgccc tggacctggg cggagcttct 1080 acccaagtga ccttcgtgcc ccagaatcag accatcgaga gccccgaca a cgccctgcag 1140 ttccggctgt acggcaagga ctacaatgtg tacacccaca gctttctgtg ctacggaaag 1200 gaccaggctc tgtggcagaa gctggccaag gacatccagg tggccagcaa cgagatcctg 1260 cgggaccctt gcttccaccc cggctacaag aaagtcgtga acgtgtccga cctgtacaag 1320 accccctgca ccaagagatt cgagatgacc ctgcccttcc ag cagttcga gatccagggc 1380 atcggcaatt accagcagtg ccaccagagc atcctggaac tgttcaacac cagctactgc 1440 ccctacagcc agtgcgcctt caacggcatc ttcctgccac ctctgcagg ggatttcggc 1500 gccttcagcg ccttctactt cgtgat gaag ttcctgaacc tgaccagcga gaaggtgtcc 1560 caggaaaaag tgacagagat gatgaagaag ttctgcgccc agccctggga ggaaatcaag 1620 acctcctacg ctggcgtgaa agagaagtac ctgagcgagt actgcttcag cggcacctac 1680 atcctgagcc tgctgctgca gggctaccac ttcaccgccg atagctggga gcacatccac 1740 ttcatcggca agattcaggg cagcgacgcc ggctggacac tgggctacat g ctgaatctg 1800 accaacatga tccccgccga gcagcccctg agcacacctc tgagccacag cacc 1854 <210> 153 <211> 625 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 153

Asp Glu Gly Lys Ala Ser Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser 1 5 10 15

Leu Gln Lys Phe Gly Glu Arg Ala Phe Lys Ala Trp Ala Val Ala Arg 20 25 30

Leu Ser Gln Arg Phe Pro Lys Ala Glu Phe Ala Glu Val Ser Lys Leu 35 40 45

Val Thr Asp Leu Thr Lys Val His Thr Glu Cys Cys His Gly Asp Leu

55 60

- 353 046596

Leu Glu Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu 65 70 75 80

Asn Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro 85 90 95

Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp Glu Met

100 105 110

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

115 120 125

Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly Met Phe

130 135 140

Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser Val Val Leu Leu 145 150 155 160

Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala

165 170 175

Ala Ala Asp Pro His Glu Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys

180 185 190

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

195 200 205

Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr

210 215 220

Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His 225 230 235 240

Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val

245 250 255

Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg

260 265 270

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

275 280 285

Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu

290 295 300

- 354 046596

Leu Ala Asp Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr 305 310 315 320

Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly

325 330 335

Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln

340 345 350

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

355 360 365

Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn

370 375 380

Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His

385 390 395 400

Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala 405 410 415

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

420 425 430

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

435 440 445

Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu

450 455 460

Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu

465 470 475 480

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

485 490 495

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

500 505 510

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

515 520 525

Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu

530 535 540

Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu

545 550 555 560

- 355 046596

Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr

565 570 575

His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile

580 585 590

Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr

595 600 605

Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser

610 615 620

Thr

625 <210> 154 <211> 1875 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 154 gacgagggta aggcatcatc tgccaagcag agattaaaat gtgcatcttt gcaaaaattt 60 ggagagagag cttttaaggc atgggctgtt gcccgactaa gccaaagatt cccaaaagcc 120 ga atttgctg aagtatccaa gctggtgact gatttgacta aagtacatac agaatgttgc 180 catggcgacc ttttagaatg tgctgatgac agagcagatt tggctaagta tatctgcgaa 240 aatcaagatt caatcagctc taagctgaag gaatgttgcg agaaaccact gttagaaaaa 300 tcgcattgta ttgctgaagt tgaaaatgat gagatgcctg ctgacttgcc ttctcttgcc 360 gctgattttg ttgagtcgaa ggatgtctgt aagaattatg ctgaagctaa agacgttttc 420 ctgggtatgt tcttatatga gtacgcaaga cgtcacccag attactctgt ggttctgcta 480 ctgagatgg ctaaaacata cgagacaacg ctggagaagt gctgtgctgc cgctgaccct 540 catgagtgct atgcaaaggt ttttgatgaa ttcaaaccag gaggcggagg atctacccag 600 aacaaggccc tgcccgagaa cgtgaagtac ggcatcgtgc tggatgccgg cagcagccac 660 accagcctgt acatctacaa gtggcctgcc gagaaagaaa acgacaccgg cgtggtgcat 720 caggtggaag agtgcagagt gaagggccct ggcatcagca agttcgtgca gaaagtgaac 780 gagatcggca tctacctgac cgactgcatg gaacgggcca gggaagtgat ccccagaagc 840 cagcaccagg aaacccccgt gt atctggga gccaccgccg gcatgagact gctgagaatg 900

- 356 046596 gaaagcgagg aactggccga ccgggtgctg gacgtggtgg aaagaagcct gagcaactac 960 ccattcgatt ttcaaggcgc cagaatcatc accggccagg aagaaggcgc ctacggctgg 1020 atcaccatca actacctgct gggcaagttc agccagaaga atcaggaa ac cttcggcgcc 1080 ctggacctgg gcggagcttc tacccaagtg accttcgtgc cccagaatca gaccatcgag 1140 agccccgaca acgccctgca gttccggctg tacggcaagg actacaatgt gtacaccac 1200 agctttctgt gctacggaaa ggaccaggct ctgt ggcaga agctggccaa ggacatccag 1260 gtggccagca acgagatcct gcgggaccct tgcttccacc ccggctacaa gaaagtcgtg 1320 aacgtgtccg acctgtacaa gaccccctgc accaagagat tcgagatgac cctgcccttc 1380 cagcagttcg agatccaggg catcggcaat taccagcagt gccaccagag catcctggaa 1440 ctgttcaaca ccagctactg cccctacagc cagt gcgcct tcaacggcat cttcctgcca 1500 cctctgcagg gggatttcgg cgccttcagc gccttctact tcgtgatgaa gttcctgaac 1560 ctgaccagcg agaaggtgtc ccaggaaaaa gtgacagaga tgatgaagaa gttctgcgcc 1620 cagccctggg agg aaatcaa gacctcctac gctggcgtga aagagaagta cctgagcgag 1680 tactgcttca gcggcaccta catcctgagc ctgctgctgc agggctacca cttcaccgcc 1740 gatagctggg agcacatcca cttcatcggc aagattcagg gcagcgacgc cggctggaca 1800 ctgggctaca tgctgaatct gaccaacatg atccccgccg agcagcccct gagcacacct 1860 ctgagccaca gcacc 1875 <210> 155 <211> 439 < 212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 155

Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu 1 5 10 15

Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala 20 25 30

Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg 35 40 45

Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile 50 55 60

Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro

- 357 046596

70 75 80

Arg Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly 85 90 95

Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu

100 105 110

Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp Phe Gln Gly

115 120 125

Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr

130 135 140

Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Thr Arg Trp Phe Ser 145 150 155 160

Ile Val Pro Tyr Glu Thr Asn Asn Gln Glu Thr Phe Gly Ala Leu Asp

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser Asn Glu Ile 225 230 235 240

Leu Arg Asp Pro Cys Phe His Pro Gly Tyr Lys Lys Val Val Asn Val

245 250 255

Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu Met Thr Leu 260 265 270

Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys

275 280 285

His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys Pro Tyr Ser

290 295 300

Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe

305 310 315 320

- 358 046596

Gly Ala Phe Ser Ala Phe Tyr Ser Val Met Lys Phe Leu Asn Leu Thr

325 330 335

Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met Lys Lys Phe

340 345 350

Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys

355 360 365

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

370 375 380

Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp Glu His Ile

385 390 395 400

His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly

405 410 415

Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln Pro Leu Ser

420 425 430

Thr Pro Leu Ser His Ser Thr

435 <210> 156 <211> 1317 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 156 acccagaaca aggccctgcc cgagaacgtg aagtacggca tcgtgctgga tgccggcagc 60 agccacacca gcctgtacat ctacaagtgg cctgccgaga aagaaaacga caccggcgtg 120 gtgcat cagg tggaagagtg cagagtgaag ggccctggca tcagcaagtt cgtgcagaaa 180 gtgaacgaga tcggcatcta cctgaccgac tgcatggaac gggccaggga agtgatcccc 240 agaagccagc accaggaaac ccccgtgtat ctgggagcca ccgccggcat gagactgctg 300 agaatggaaa gcgaggaact ggccgaccgg gtgctggacg tggtggaaag aagcctgagc 360 aactacccat tcgattttca aggcgccaga atcatcaccg gccaggaaga aggcgcctac 420 ggctggatca ccatcaacta cctgctgggc aagttcagcc agaagaccag atggttcagc 480 atcgtgccct acgagacaaa caatcaggaa accttcggcg ccctggacct gggcggagct 540 tctacccaag tgaccttcgt gccccagaat cagaccatcg agagccccga caacgccctg 600

- 359 046596 cagttccggc tgtacggcaa ggactacaat gtgtacaccc acagctttct gtgctacgga 660 aaggaccagg ctctgtggca gaagctggcc aaggacatcc aggtggccag caacgagatc 720 ctgcgggacc cttgcttcca ccccggctac aagaaagtcg t gaacgtgtc cgacctgtac 780 aagaccccct gcaccaagag attcgagatg accctgccct tccagcagtt cgagatccag 840 ggcatcggca attaccagca gtgccaccag agcatcctgg aactgttcaa caccagctac 900 tgcccctaca gccagtgcgc cttcaacggc atcttcctg c cacctctgca gggggatttc 960 ggcgccttca gcgccttcta ctccgtgatg aagttcctga acctgaccag cgagaaggtg 1020 tcccaggaaa aagtgacaga gatgatgaag aagttctgcg cccagccctg ggaggaaatc 1080 aagacctcct acgctggcgt gaaagagaag tacctgagcg agtactgctt cagcggcacc 1140 tacatcctga gcctgctgct gcagggctac cactt caccg ccgatagctg ggagcacatc 1200 cacttcatcg gcaagattca gggcagcgac gccggctgga cactgggcta catgctgaat 1260 ctgaccaaca tgatccccgc cgagcagccc ctgagcacac ctctgagcca cagcacc 1317 <210> 157 <211> 90 <212> DNA < 213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 157 tcgcgatcct ggaaggcgtg cactgcgccc ctaccagcag cagcaccaag aaaacccagc 60 tgaccagcag cacccagaac aaggccctgc 90 <210> 158 <211> 18 <212> DNA <213> Artificial sequence <220 >

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 158 tagaaggcac agtcgagg 18 <210> 159 <211> 66 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer

- 360 046596 <400> 159 ctggtcgcga tcctggaagg cgtgcactgc gcccctacca gcagcagcac ccagaacaag 60 gccctg 66 <210> 160 <211> 66 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 160 ctggtcgcga tcctggaagg cgtgcactgc gcccctacca gcagcagcac ccagaacaag 60 gccctg 66 <210> 161 <211> 57 <212> DNA <213> Artificial sequence <22 0>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 161 ctggtcgcga tcctggaagg cgtgcactgc gcccctacca cccagaacaa ggccctg 57 <210> 162 <211> 75 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 162 ctggtcgcga tcctggaagg cgtgcactgc gcccctacca gcagcagcac caagaaaacc 60 cagaacaagg ccctg 75 <210> 163 <211> 84 <212> DNA Artificial <213> sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 163 ctggtcgcga tcctggaagg cgtgcactgc gcccctacca gcagcagcac caagaaaacc 60

- 361 046596 cagctgaccc agaacaaggc cctg 84 <210> 164 <211> 75 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 164 ctggtcgcga tcctggaagg cgtgcactgc agcagcagca ccaagaaaac ccagctgacc 60 cagaacaagg ccctg 75 <210> 165 <211> 16 <212> DNA <213> artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 165 catacgattt aggtga 16 <210> 166 <211> 18 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 166 tagaaggcac agtcgagg 18 <210> 167 <211> 76 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 167

Met Gln Ile Phe Val Lys Thr Leu Thr Gly Lys Thr Ile Thr Leu Glu

5 10 15

Val Glu Pro Ser Asp Thr Ile Glu Asn Val Lys Ala Lys Ile Gln Asp 20 25 30

- 362 046596

Lys Glu Gly Ile Pro Pro Asp Gln Gln Arg Leu Ile Phe Ala Gly Lys 35 40 45

Gln Leu Glu Asp Gly Arg Thr Leu Ser Asp Tyr Asn Ile Gln Lys Glu 50 55 60

Ser Thr Leu His Leu Val Leu Arg Leu Arg Gly Gly 65 70 75 <210> 168 <211> 105 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 168

Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln 1 5 10 15

Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr 20 25 30

Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser 35 40 45

Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr 50 55 60

Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys 65 70 75 80

His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro 85 90 95

Val Thr Lys Ser Phe Asn Arg Gly Glu

100 105 <210> 169 <211> 186 <212> PROTEIN <213> Homo sapiens <400> 169

Asp Ala His Lys Ser Glu Val Ala His Arg Phe Lys Asp Leu Gly Glu 1 5 10 15

Glu Asn Phe Lys Ala Leu Val Leu Ile Ala Phe Ala Gln Tyr Leu Gln 20 25 30

- 363 046596

Gln Ser Pro Phe Glu Asp His Val Lys Leu Val Asn Glu Val Thr Glu 35 40 45

Phe Ala Lys Thr Cys Val Ala Asp Glu Ser Ala Glu Asn Cys Asp Lys 50 55 60

Ser Leu His Thr Leu Phe Gly Asp Lys Leu Cys Thr Val Ala Thr Leu 65 70 75 80

Arg Glu Thr Tyr Gly Glu Met Ala Asp Cys Cys Ala Lys Gln Glu Pro 85 90 95

Glu Arg Asn Glu Cys Phe Leu Gln His Lys Asp Asp Asn Pro Asn Leu

100 105 110

Pro Arg Leu Val Arg Pro Glu Val Asp Val Met Cys Thr Ala Phe His

115 120 125

Asp Asn Glu Glu Thr Phe Leu Lys Lys Tyr Leu Tyr Glu Ile Ala Arg

130 135 140

Arg His Pro Tyr Phe Tyr Ala Pro Glu Leu Leu Phe Phe Ala Lys Arg 145 150 155 160

Tyr Lys Ala Ala Phe Thr Glu Cys Cys Gln Ala Ala Asp Lys Ala Ala

165 170 175

Cys Leu Leu Pro Lys Leu Asp Glu Leu Arg

180 185 <210> 170 <211> 193 <212> PROTEIN <213> Homo sapiens <400> 170

Asp Glu Gly Lys Ala Ser Ser Ala Lys Gln Arg Leu Lys Cys Ala Ser 1 5 10 15

Leu Gln Lys Phe Gly Glu Arg Ala Phe Lys Ala Trp Ala Val Ala Arg 20 25 30

Leu Ser Gln Arg Phe Pro Lys Ala Glu Phe Ala Glu Val Ser Lys Leu 35 40 45

Val Thr Asp Leu Thr Lys Val His Thr Glu Cys Cys His Gly Asp Leu 50 55 60

- 364 046596

Leu Glu Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile Cys Glu 65 70 75 80

Asn Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu Lys Pro 85 90 95

Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp Glu Met

100 105 110

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

115 120 125

Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly Met Phe

130 135 140

Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser Val Val Leu Leu 145 150 155 160

Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Glu Lys Cys Cys Ala

165 170 175

Ala Ala Asp Pro His Glu Cys Tyr Ala Lys Val Phe Asp Glu Phe Lys

180 185 190

Pro <210> 171 <211> 30 <212> DNA <213> Artificial Sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 171 ctgccgagaa agaacaggac accggcgtgg 30 <210> 172 <211> 30 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 172 ccacgccggt gtcctgttct ttctcggcag 30

- 365 046596 <210> 173 <211> 29 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 173 cgtgccccag aatcaggcca tcgagagcc 29 <210> 174 <211> 29 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 174 ggctctcgat ggcctgattc tggggcacg 29 <210> 175 <211> 41 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 175 ggctacaaga aagtcgtgca ggtgtccgac ctgtacaaga c 41 <210> 176 <211> 41 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 176 gtcttgtaca ggtcggacac ctgcacgact ttcttgtagc c 41 <210> 177 <211> 35 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer

- 366 046596 <400> 177 gcatcctgga actgttccag accagctact gcccc 35 <210> 178 <211> 35 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 178 ggggcagtag ctggtctgga acagttccag gatgc 35 <210> 179 <211> 35 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 179 ccgtgatgaa gttcctgcag ctgaccagcg agaag 35 <210> 180 <211> 35 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 180 cttctcgctg gtcagctgca ggaacttcat cacgg 35 <210> 181 <211> 36 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 181 cactgggcta catgctgcag ctgaccaaca tgatcc 36 <210> 182 <211> 36 <212> DNA <213> Artificial sequence

- 367 046596 <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 182 ggatcatgtt ggtcagctgc agcatgtagc ccagtg 36 <210> 183 <211> 39 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 183 ctacatcctg agcctgctgc agcagggcta ccacttcac 39 <210> 184 <211> 39 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 184 gtgaagtggt agccctgctg cagcaggctc aggatgtag 39 <210> 185 <211> 43 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 185 gagaagtacc tgagcgagtt ttgcttcagc ggcacctaca tcc 43 <210> 186 <211> 43 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 186 ggatgtaggt gccgctgaag caaaactcgc tcaggtactt ctc 43 <210> 187 <211> 36

- 368 046596 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 187 gttcgagatc cagggcaccg gcaattacca gcagtg 36 <210> 188 <211> 36 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 188 cactgctggt aattgccggt gccctggatc tcgaac 36 <210> 189 <211> 37 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 189 cgccgatagc tgggagcaca tccacttcat cggcaag 37 <210> 190 <211> 37 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 190 cttgccgatg aagtggatgt gctcccagct atcggcg 37 <210> 191 <211> 120 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 191 gagatcggca tctacctgac cgactgcatg gaacgggcca tggaagtgat ccccagaagc 60

- 369 046596 cagcaccagg aaacccccgt gtatctggga gccaccgccg gcatgagact gctgagaatg 120 <210> 192 <211> 25 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 192 gagatcggca tctacctgac cgact 25 <210> 193 <211> 18 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 193 cattctcagc agtctcat 18 <210> 194 <211> 120 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 194 cttcagcgcc ttctactccg tgatgaagtt cctgaacctg accagcgaga aggtgtccca 60 ggaaaaagtg acagagatga tgaagaagtt ctgcgcccag ccctgggagg aaatcaagac 120 < 210> 195 <211> 19 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 195 cttcagcgcc ttctactcc 19 <210> 196 <211> 19 <212> DNA <213> Artificial sequence

- 370 046596 <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 196 ggtcttgatt tcctcccag 19 <210> 197 <211> 119 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 197 ctgggaggaa atcaagacct cctacgctgg cgtgaaagag aagtacctga gcgagttctg 60 cttcagcggc acctacatcc tgagcctgct gctgcagggc taccacttca ccgccgata 119 <21 0> 198 <211> 119 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 198 ctgggaggaa atcaagacct cctacgctgg cgtgaaagag aagtacctga gcgagtactg 60 cttcagcggc acctacatcc tgagcctgct gcagcagggc taccacttca ccgccgata 119 > 199 <211> 119 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 199 ctgggaggaa atcaagacct cctacgctgg cgtgaaagag aagtacctga gcgagttctg 60 cttcagcggc acctacatcc tgagcctgct gcagcagggc taccacttca ccgccgata 119 0> 200 <211> 19 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer

- 371 046596 <400> 200 ctgggaggaa atcaagacc 19 <210> 201 <211> 19 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 201 tatcggcggt gaagtggta 19 <210> 202 <211> 119 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 202 ctgggaggaa atcaagacct cctacgctgg cgtgaaagag aagtacctga gcgagtactg 60 cttcagcggc acctacatcc tgagcctgct gctgcagggc taccacttca ccgccgata 119 > 203 <211> 26 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 203 caccggccag gaagccggcg cctacg 26 <210> 204 <211> 26 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 204 cgtaggcgcc ggcttcctgg ccggtg 26 <210> 205 <211> 34 <212> DNA <213> Artificial sequence

- 372 046596 <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 205 ggacctgggc ggagctgcta cccaagtgac cttc 34 <210> 206 <211> 34 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 206 gaaggtcact tgggtagcag ctccgcccag gtcc 34 <210> 207 <211> 80 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 207 ctggatcacc atcaactacc tgctgggcaa gttcagccag aagaccagat ggttcagcat 60 cgtgccctac gagacaaaca 80 <210> 208 <211> 69 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic primer <400> 208 tcacttgggt agaagctccg cccaggtcca gggcgccgaa ggtttcctga ttgtttgtct 60 cgtagggca 69 <210> 209 <211> 430 <212> PROTEIN <213> sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 209

- 373 046596

Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly 1 5 10 15

Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys 20 25 30

Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu 35 40 45

Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val 50 55 60

Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu 65 70 75 80

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

90 95

Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp

100 105 110

Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp

115 120 125

Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly

130 135 140

Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln 145 150 155 160

Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr

165 170 175

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

180 185 190

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

195 200 205

Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile

210 215 220

Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly

225 230 235 240

Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr

245 250 255

- 374 046596

Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly

260 265 270

Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn

275 280 285

Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu

290 295 300

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

305 310 315 320

Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val

325 330 335

Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys

340 345 350

Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe

355 360 365

Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr

370 375 380

Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser

385 390 395 400

Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile

405 410 415

Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430 <210> 210 <211> 1290 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 210 gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60 gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120 gtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180

- 375 046596 gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccatggaa 240 gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300 agactgctga gaatggaaag cgaggaactg gccgaccggg tgct ggacgt ggtggaaaga 360 agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420 ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480 gaaaccttcg gcgccctgga cctgggcgga c aagtgacctt cgtgccccag 540 aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600 aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660 gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720 tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc caccaa gagattcgag 780 atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840 cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900 ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcag cgcctt ctacttcgtg 960 atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020 aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080 aagtacctga gcgagtactg cttcagcggc acctacatcc tgagcctgct gctgcagggc 1140 taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat cagggcagc 1200 gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260 cccctgagca cacctctgag ccacagcacc 1290 <210> 211 <211>430 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 211

Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly 1 5 10 15

Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys 20 25 30

Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu 35 40 45

Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val

- 376 046596

55 60

Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu 65 70 75 80

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

90 95

Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp

100 105 110

Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp

115 120 125

Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly

130 135 140

Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln 145 150 155 160

Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr

165 170 175

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

180 185 190

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

195 200 205

Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile

210 215 220

Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly

225 230 235 240

Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr

245 250 255

Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly

260 265 270

Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn

275 280 285

Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu

290 295 300

- 377 046596

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

305 310 315 320

Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val

325 330 335

Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys

340 345 350

Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe

355 360 365

Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr

370 375 380

Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser

385 390 395 400

Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile

405 410 415

Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430 <210> 212 <211> 1290 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 212 gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60 gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120 gtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180 gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccatggaa 240 gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300 agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360 agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420 ggcgcctacg gct ggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480 gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540 aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600

- 378 046596 aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660 gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720 tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780 atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840 cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900 ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctacttcgtg 960 atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020 aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080 aagtacctga gcgagttttg cttcagcggc acctacatcc tgagcctgct gctgcagggc 1140 taccacttca ccgccgatag ctgggagcac atccact tca tcggcaagat tcagggcagc 1200 gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260 cccctgagca cacctctgag ccacagcacc 1290 <210> 213 <211>433 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 213

Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val 1 5 10 15

Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr 20 25 30

Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His 35 40 45

Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val 50 55 60

Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg 65 70 75 80

Ala Met Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr 85 90 95

Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu

100 105 110

- 379 046596

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

115 120 125

Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly

130 135 140

Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln 145 150 155 160

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

165 170 175

Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn

180 185 190

Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His

195 200 205

Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala 210 215 220

Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe 225 230 235 240

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

245 250 255

Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu

260 265 270

Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu

275 280 285

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

290 295 300

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

305 310 315 320

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

325 330 335

Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu

340 345 350

- 380 046596

Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu

355 360 365

Phe Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr

370 375 380

His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile

385 390 395 400

Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr

405 410 415

Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser

420 425 430

Thr <210> 214 <211> 1299 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 214 gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60 gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120 ga aaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180 agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240 gccatggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300 gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360 gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420 caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480 aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540 gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600 aaggactaca tacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660 cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720 caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780 agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840

- 381 046596 cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900 gccttcaacg gcatcttcct gccacctctg caggggggatt tcggcgcctt cagcgccttc 960 tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020 gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080 gtgaaagaga agtacctgag cgagttctgc ttcagcggca cctacatcct gagcctgctg 1140 ctgcagggct accacttcac c gccgatagc tgggagcaca tccacttcat cggcaagatt 1200 cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260 gccgagcagc ccctgagcac acctctgagc cacagcacc 1299 <210> 215 <211> 442 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 215

Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Thr Ser Ser Thr 1 5 10 15

Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu Asp 20 25 30

Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu 35 40 45

Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val 50 55 60

Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly 65 70 75 80

Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu Val Ile Pro Arg 85 90 95

Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met

100 105 110

Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp

115 120 125

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

130 135 140

- 382 046596

Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile 145 150 155 160

Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe Gly

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser

225 230 235 240

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

245 250 255

Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu

260 265 270

Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr

275 280 285

Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys

290 295 300

Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln

305 310 315 320

Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu

325 330 335

Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met

340 345 350

Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala

355 360 365

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

370 375 380

Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp

- 383 046596

385 390 395 400

Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp

405 410 415

Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln

420 425 430

Pro Leu Ser Thr Pro Leu Ser His Ser Thr

435 440 <210> 216 <211> 1326 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 216 gcccctacca gcagcagcac caagaaaacc cagctgacca gcagcaccca gaacaaggcc 60 ctgcccgaga acgtgaagta cggcatcgtg ctggatgccg gcagcagcca caccagcctg 120 tacatcta ca agtggcctgc cgagaaagaa aacgacaccg gcgtggtgca tcaggtggaa 180 gagtgcagag tgaagggccc tggcatcagc aagttcgtgc agaaagtgaa cgagatcggc 240 atctacctga ccgactgcat ggaacgggcc atggaagtga tccccagaag ccagcaccag 300 gaaacccccg tgtatctggg agccaccgcc ggcatgagac tgctgagaat ggaaagcgag 360 gaactggccg accgggtgct ggacgtggtg gaaagaagcc tgagcaacta cccattcgat 420 tttcaaggcg cca gaatcat caccggccag gaagaaggcg cctacggctg gatcaccatc 480 aactacctgc tgggcaagtt cagccagaag aatcaggaaa ccttcggcgc cctggacctg 540 ggcggagctt ctacccaagt gaccttcgtg ccccagaatc agaccatcga gagccccgac 600 agttccggct gtacggcaag gactacaatg tgtacaccca cagctttctg 660 tgctacggaa aggaccaggc tctgtggcag aagctggcca aggacatcca ggtggccagc 720 aacgagatcc tgcgggaccc ttgcttccac cccggctaca agaaagtcgt gaacgtgtcc 780 gacctgtaca agaccccctg caccaagaga ttcgagatga ccctgccctt ccagcagttc 840 gagatccagg gcatcggcaa ttacc agcag tgccaccaga gcatcctgga actgttcaac 900 accagctact gcccctacag ccagtgcgcc ttcaacggca tcttcctgcc acctctgcag 960 ggggatttcg gcgccttcag cgccttctac ttcgtgatga agttcctgaa cctgaccagc 1020 gagaaggtgt c caggaaaa agtgacagag atgatgaaga agttctgcgc ccaaccctgg 1080 gaggaaatca agacctccta cgctggcgtg aacgagaagt acctgagcga gttttgcttc 1140

- 384 046596 agcggcacct acatcctgag cctgctgctg cagggctacc acttcaccgc cgatagctgg 1200 gagcacatcc acttcatcgg caagattcag ggcagcgacg ccggctggac actgggctac 1260 atgctgaatc tgaccaacat gatccccgcc gagcagcccc tgagcacacc tct gagccac 1320 agcacc 1326 <210> 217 <211>430 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 217

Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly 1 5 10 15

Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys 20 25 30

Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu 35 40 45

Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val 50 55 60

Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu 65 70 75 80

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

90 95

Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp

100 105 110

Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp

115 120 125

Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly

130 135 140

Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln 145 150 155 160

Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr

165 170 175

- 385 046596

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

180 185 190

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

195 200 205

Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile

210 215 220

Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly

225 230 235 240

Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr

245 250 255

Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly

260 265 270

Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn

275 280 285

Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu

290 295 300

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

305 310 315 320

Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val

325 330 335

Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys

340 345 350

Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe

355 360 365

Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr

370 375 380

Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser

385 390 395 400

Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile

405 410 415

- 386 046596

Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430 <210> 218 <211> 1290 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 218 gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60 gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120 gtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180 gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccatggaa 240 gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300 agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360 agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420 ggcgcctacg gct ggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480 gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540 aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600 aatgt gtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660 gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720 tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780 atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840 cagagcatcc tggaactgtt caac accagc tactgcccct acagccagtg cgccttcaac 900 ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctacttcgtg 960 atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020 aagaagttct g cgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080 aagtacctga gcgagttctg cttcagcggc acctacatcc tgagcctgct gcagcagggc 1140 taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat tcagggcagc 1200 gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260 cccctgagca cacctctgag ccacagcacc 129 0 <210> 219 <211> 433 <212> PROTEIN

- 387 046596 <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 219

Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val 1 5 10 15

Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr 20 25 30

Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His 35 40 45

Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val 50 55 60

Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg 65 70 75 80

Ala Met Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr 85 90 95

Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu

100 105 110

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

115 120 125

Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly

130 135 140

Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln 145 150 155 160

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

165 170 175

Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn

180 185 190

Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His

195 200 205

Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala 210 215 220

- 388 046596

Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe 225 230 235 240

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

245 250 255

Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu

260 265 270

Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu

275 280 285

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

290 295 300

Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe 305 310 315 320

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

325 330 335

Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu

340 345 350

Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu

355 360 365

Phe Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr

370 375 380

His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile

385 390 395 400

Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr 405 410 415

Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser

420 425 430

Thr <210> 220 <211> 1299 <212> DNA <213> Artificial sequence

- 389 046596 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 220 gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60 gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120 ga aaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180 agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240 gccatggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300 gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360 gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420 caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480 aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540 gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600 aaggactaca tacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660 cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720 caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780 agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840 cagtgccacc agagcatcct ggaactgt tc aacaccagct actgccccta cagccagtgc 900 gccttcaacg gcatcttcct gccacctctg caggggggatt tcggcgcctt cagcgccttc 960 tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020 gagatgatga agaagtt ctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080 gtgaaagaga agtacctgag cgagttctgc ttcagcggca cctacatcct gagcctgctg 1140 cagcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200 cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260 gccgagcagc ccctgagcac acctctgagc cacagcacc 1299 <210> 221 <211>430 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 221

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

5 10 15

- 390 046596

Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys 20 25 30

Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu 35 40 45

Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val 50 55 60

Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu 65 70 75 80

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

90 95

Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp

100 105 110

Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp

115 120 125

Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly

130 135 140

Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln 145 150 155 160

Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr

165 170 175

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

180 185 190

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

195 200 205

Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile

210 215 220

Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly

225 230 235 240

Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr

245 250 255

- 391 046596

Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly

260 265 270

Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn

275 280 285

Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu

290 295 300

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

305 310 315 320

Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val

325 330 335

Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys

340 345 350

Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe

355 360 365

Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr

370 375 380

Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser

385 390 395 400

Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile

405 410 415

Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430 <210> 222 <211> 1290 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 222 gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60 gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120 gtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180 gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccatggaa 240

- 392 046596 gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300 agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360 agcctgagca actacccatt cgattttcaa ggcgccagaa t catcaccgg ccaggaagaa 420 ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480 gaaaccttcg gcgccttgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540 aatcagacca tcgagagccc cgacaacgcc ctg cagttcc ggctgtacgg caaggactac 600 aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660 gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720 tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780 atgaccctgc ccttccagca gttcgagatc cagggcatcg acca gcagtgccac 840 cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900 ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctactccgtg 960 atgaagttcc tgaacctgac cagcgagaag gtgtcccagg a aaaagtgac agagatgatg 1020 aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080 aagtacctga gcgagtactg cttcagcggc acctacatcc tgagcctgct gctgcagggc 1140 taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat tcagggcagc 1200 gacgccggct ggacactggg ttacatgctg aatctgacca acatgatccc cgcc gagcag 1260 cccctgagca cacctctgag ccacagcacc 1290 <210> 223 <211>433 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 223

Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val 1 5 10 15

Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr 20 25 30

Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His 35 40 45

Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val

55 60

- 393 046596

Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg 65 70 75 80

Ala Met Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr 85 90 95

Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu

100 105 110

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

115 120 125

Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly

130 135 140

Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln 145 150 155 160

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

165 170 175

Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn

180 185 190

Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His

195 200 205

Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala 210 215 220

Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe 225 230 235 240

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

245 250 255

Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu

260 265 270

Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu

275 280 285

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

290 295 300

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

- 394 046596

305 310 315 320

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

325 330 335

Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu

340 345 350

Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu

355 360 365

Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr

370 375 380

His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile

385 390 395 400

Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr 405 410 415

Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser

420 425 430

Thr <210> 224 <211> 1299 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 224 gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60 gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120 ga aaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180 agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240 gccatggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300 gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360 gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420 caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480 aagaatcagg aaaccttcgg cgccttggac ctgggcggag cttctaccca agtgaccttc 540

- 395 046596 gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600 aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660 cagaagctgg ccaaggacat ccaggtggcc agcaacgaga t cctgcggga cccttgcttc 720 caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780 agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840 cagtgccacc agagcatcct ggaactgttc aacaccagct act gccccta cagccagtgc 900 gccttcaacg gcatcttcct gccacctctg caggggggatt tcggcgcctt cagcgccttc 960 tactccgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020 gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080 gtgaaagaga agtacctgag cgagtactgc t tcagcggca cctacatcct gagcctgctg 1140 ctgcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200 cagggcagcg acgccggctg gacactgggt tacatgctga atctgaccaa catgatcccc 1260 gccgagcagc ccctgagcac acctctgag c cacagcacc 1299 <210> 225 <211>430 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 225

Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly 1 5 10 15

Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys 20 25 30

Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu 35 40 45

Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val 50 55 60

Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu 65 70 75 80

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

90 95

- 396 046596

Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp

100 105 110

Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp

115 120 125

Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly

130 135 140

Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln 145 150 155 160

Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr

165 170 175

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

180 185 190

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

195 200 205

Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile

210 215 220

Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly

225 230 235 240

Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr

245 250 255

Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly

260 265 270

Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn

275 280 285

Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu

290 295 300

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

305 310 315 320

Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val

325 330 335

Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys

340 345 350

- 397 046596

Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Phe Cys Phe

355 360 365

Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr

370 375 380

Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser

385 390 395 400

Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile

405 410 415

Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430 <210> 226 <211> 1290 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 226 gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60 gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120 gtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180 gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccagggaa 240 gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300 agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360 agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420 ggcgcctacg gct ggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480 gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540 aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600 aatgt gtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660 gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720 tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780 atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840 cagagcatcc tggaactgtt caac accagc tactgcccct acagccagtg cgccttcaac 900

- 398 046596 ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctacttcgtg 960 atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020 aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080 aagtacctga gcgagttttg cttcagcggc acctacatcc tgagcctgct gcagcagggc 1140 taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat tcagggcagc 1200 gacgccggct ggacactggg c tacatgctg aatctgacca acatgatccc cgccgagcag 1260 cccctgagca cacctctgag ccacagcacc 1290 < 210> 227 <211>433 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 227

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

5 10 15

Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr 20 25 30

Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His 35 40 45

Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val 50 55 60

Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg 65 70 75 80

Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr 85 90 95

Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu

100 105 110

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

115 120 125

Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly

130 135 140

Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln

- 399 046596

145 150 155 160

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

165 170 175

Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn

180 185 190

Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His

195 200 205

Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala 210 215 220

Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe 225 230 235 240

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

245 250 255

Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu

260 265 270

Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu

275 280 285

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

290 295 300

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

305 310 315 320

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

325 330 335

Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu

340 345 350

Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu

355 360 365

Phe Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr

370 375 380

His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile

385 390 395 400

- 400 046596

Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr

405 410 415

Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser

420 425 430

Thr <210> 228 <211> 1299 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 228 gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60 gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120 ga aaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180 agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240 gccagggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300 gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360 gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420 caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480 aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540 gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600 aaggactaca tacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660 cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720 caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780 agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840 cagtgccacc agagcatcct ggaactgt tc aacaccagct actgccccta cagccagtgc 900 gccttcaacg gcatcttcct gccacctctg caggggggatt tcggcgcctt cagcgccttc 960 tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020 gagatgatga agaagtt ctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080 gtgaaagaga agtacctgag cgagttttgc ttcagcggca cctacatcct gagcctgctg 1140 cagcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200

- 401 046596 CAGGGGCAGCG ACGCCGCTG GACACTGGC TACTGACCA CATGATGATCCCCCCCCCCCCCC 1260 GCCGAGCAGCACCCCCCCCCCCCCCCCCcAGCACC 1299 <22> 229 <2 211> 430 <12 212> Belok <2 21 3> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 229

Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly 1 5 10 15

Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys 20 25 30

Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu 35 40 45

Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val 50 55 60

Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu 65 70 75 80

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

90 95

Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp

100 105 110

Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp

115 120 125

Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly

130 135 140

Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln 145 150 155 160

Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr

165 170 175

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

180 185 190

- 402 046596

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

195 200 205

Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile

210 215 220

Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly

225 230 235 240

Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr

245 250 255

Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly

260 265 270

Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn

275 280 285

Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu

290 295 300

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

305 310 315 320

Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val

325 330 335

Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys

340 345 350

Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe

355 360 365

Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr

370 375 380

Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser

385 390 395 400

Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile

405 410 415

Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430

- 403 046596 <210> 230 <211> 1290 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 230 gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggac 60 gccggctcct cccacacctc cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120 cgtgg tgcaccaagt ggaagagtgc agagtgaagg gccccggcat ctccaagttc 180 gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccagagaa 240 gtgatccctc ggtcccagca ccaggaaacc cctgtctacc tgggcgccac cgccggcatg 300 cggctgctgc ggatggaatc cgaggaactg gccgaccggg tgctggacgt ggtggaacgg 360 tccctgtcca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagag 420 ggcgcctacg gctgg atcac catcaactac ctgctgggca agttctccca gaagaatcag 480 gaaaccttcg gcgccctgga cctgggcgga gccagcaccc aagtcacatt cgtgccccag 540 aaccagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600 aacgtgtaca cccacagctt tctgtgctac ggcaaggacc aggccctgtg gcagaagctg 660 gccaaggaca tccaagtggc ctccaacgag atcctgcggg acccctgctt ccaccccggc 720 tacaagaaag tggtcaacgt gtccgacctg tacaagaccc cttgcaccaa gagattcgag 780 atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaactacca gcagtgccac 840 cagtccatcc tggaactgtt ca acacctcc tactgcccct actcccagtg cgccttcaac 900 ggcatcttcc tgcctccact gcagggcgac ttcggcgcct tctccgcctt ctactccgtg 960 atgaagttcc tgaacctgac ctccgagaaa gtgtcccagg aaaaagtgac cgagatgatg 1020 aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080 aagtacctgt ccgagtactg cttctccggc acctacatcc tgtccctgct gctgcagggc 1140 taccacttca ccgccgacag ctgggagcac atccacttca tcggcaagat ccagggatcc 1200 gacgctggct ggaccctggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260 cccctgtcca cccctctgtc tcactccacc 129 0 <210> 231 <211> 433 <212> PROTEIN <213> Artificial sequence <220>

<221> source

- 404 046596 <223> /note=Description of artificial sequence: synthetic polypeptide <400> 231

Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val 1 5 10 15

Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr 20 25 30

Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His 35 40 45

Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val 50 55 60

Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg 65 70 75 80

Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr 85 90 95

Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu

100 105 110

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

115 120 125

Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly

130 135 140

Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln 145 150 155 160

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

165 170 175

Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn

180 185 190

Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His

195 200 205

Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala 210 215 220

Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe 225 230 235 240

- 405 046596

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

245 250 255

Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu

260 265 270

Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu

275 280 285

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

290 295 300

Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe 305 310 315 320

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

325 330 335

Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu

340 345 350

Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu

355 360 365

Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr

370 375 380

His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile

385 390 395 400

Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr 405 410 415

Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser

420 425 430

Thr <210> 232 <211> 1299 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide

- 406 046596 <400> 232 gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60 gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120 gaaaacgaca ccggcgtggt gcatca ggtg gaagagtgca gagtgaaggg ccctggcatc 180 agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240 gccagggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300 gccggcatga gactgctgag aatggaa agc gaggaactgg ccgaccgggt gctggacgtg 360 gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420 caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480 aagaatcagg aaaccttcgg cgccttggac ctgggcggag cttctaccca agtgaccttc 540 gtgcccca ga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600 aaggactaca atgtgtacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660 cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720 caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780 agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840 cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900 gccttcaacg gcatcttcct gccacctctg caggggatt tcggcgcctt cagcgccttc 960 tactccgtga tgaagtt cct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020 gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080 gtgaaagaga agtacctgag cgagtactgc ttcagcggca cctacatcct gagcctgctg 1140 ctgcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200 cagggcagcg acgccggctg gacactgggt tacatgctga atctgaccaa catgatcccc 1260 gccgagcagc ccctgagcac acctctgagc cacagcacc 1299 <210> 233 <211>430 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 233

Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly 1 5 10 15

Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys

25 30

- 407 046596

Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu 35 40 45

Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val 50 55 60

Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Met Glu 65 70 75 80

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

90 95

Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp

100 105 110

Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp

115 120 125

Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly

130 135 140

Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln 145 150 155 160

Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr

165 170 175

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

180 185 190

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

195 200 205

Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile

210 215 220

Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly

225 230 235 240

Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr

245 250 255

Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly

260 265 270

- 408 046596

Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn

275 280 285

Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu

290 295 300

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

305 310 315 320

Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val

325 330 335

Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys

340 345 350

Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe

355 360 365

Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr

370 375 380

Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser

385 390 395 400

Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile

405 410 415

Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430 <210> 234 <211> 1290 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 234 gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60 gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120 gtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180 gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccatggaa 240 gtgatcccca gaagccagca cccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300 agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360

- 409 046596 agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420 ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480 gaaaccttcg gcgccctgga cctgggcgga gcttctaccc a agtgacctt cgtgccccag 540 aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600 aatgtgtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660 gccaaggaca tccaggtggc cagcaacgag ggg acccttgctt ccaccccggc 720 tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780 atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840 cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900 ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcg cctt ctactccgtg 960 atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020 aagaagttct gcgcccagcc ctgggaggaa atcaagacct cctacgctgg cgtgaaagag 1080 aagtacctga gcgagtactg cttcagcggc acctacatcc tgagcctgct gcagcagggc 1140 taccacttca ccgccgatag ctgggagcac atccacttca tcggcaagat tcagggcagc 1200 gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260 cccctgagca cacctctgag ccacagcacc 1290 <210> 235 <211>433 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 235

Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val 1 5 10 15

Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr 20 25 30

Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His 35 40 45

Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val 50 55 60

Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg

70 75 80

- 410 046596

Ala Met Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr 85 90 95

Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu

100 105 110

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

115 120 125

Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly

130 135 140

Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln 145 150 155 160

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

165 170 175

Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn

180 185 190

Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His

195 200 205

Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala 210 215 220

Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe 225 230 235 240

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

245 250 255

Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu

260 265 270

Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu

275 280 285

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

290 295 300

Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe 305 310 315 320

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

- 411 046596

325 330 335

Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu

340 345 350

Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu

355 360 365

Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr

370 375 380

His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile

385 390 395 400

Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr 405 410 415

Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser

420 425 430

Thr <210> 236 <211> 1299 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 236 gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60 gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120 ga aaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180 agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240 gccatggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300 gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360 gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420 caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480 aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540 gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600 aaggactaca tacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660

- 412 046596 cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720 caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780 agattcgaga tgaccctgcc cttccagcag ttcgagatcc aggg catcgg caattaccag 840 cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta cagccagtgc 900 gccttcaacg gcatcttcct gccacctctg caggggggatt tcggcgcctt cagcgccttc 960 tactccgtga tgaagttcct gaacctgacc agcgagaagg tgt cccagga aaaagtgaca 1020 gagatgatga agaagttctg cgcccagccc tgggaggaaa tcaagacctc ctacgctggc 1080 gtgaaagaga agtacctgag cgagtactgc ttcagcggca cctacatcct gagcctgctg 1140 cagcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200 cagggcagcg acgccggctg gacactgggc tacatgctga atct gaccaa catgatcccc 1260 gccgagcagc ccctgagcac acctctgagc cacagcacc 1299 <210> 237 <211>430 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 237

Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly 1 5 10 15

Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys 20 25 30

Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu 35 40 45

Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val 50 55 60

Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu 65 70 75 80

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

90 95

Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp

100 105 110

- 413 046596

Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp

115 120 125

Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly

130 135 140

Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln 145 150 155 160

Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr

165 170 175

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

180 185 190

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

195 200 205

Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile

210 215 220

Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly 225 230 235 240

Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr

245 250 255

Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly

260 265 270

Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn

275 280 285

Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu

290 295 300

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

305 310 315 320

Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val

325 330 335

Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys

340 345 350

Thr Ser Tyr Ala Gly Val Asn Glu Lys Tyr Leu Ser Glu Phe Cys Phe

355 360 365

- 414 046596

Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr

370 375 380

Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser

385 390 395 400

Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile

405 410 415

Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430 <210> 238 <211> 1290 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 238 gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60 gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120 gtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180 gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcatggaacg ggccagggaa 240 gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300 agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360 agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccaggaagaa 420 ggcgcctacg gct ggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480 gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540 aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600 aatgt gtaca cccacagctt tctgtgctac ggaaaggacc aggctctgtg gcagaagctg 660 gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720 tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780 atgaccctgc ccttccagca gttcgagatc cagggcatcg gcaattacca gcagtgccac 840 cagagcatcc tggaactgtt caac accagc tactgcccct acagccagtg cgccttcaac 900 ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctacttcgtg 960 atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020

- 415 046596 aagaagttct gcgcccaacc ctgggaggaa atcaagacct cctacgctgg cgtgaacgag 1080 aagtacctga gcgagttttg cttcagcggc acctacatcc tgagcctgct gctgcagggc 1140 taccacttca ccgccgatag ctgggagcac atccactt ca tcggcaagat tcagggcagc 1200 gacgccggct ggacactggg ctacatgctg aatctgacca acatgatccc cgccgagcag 1260 cccctgagca cacctctgag ccacagcacc 1290 <210> 239 <211>433 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 239

Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val 1 5 10 15

Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr 20 25 30

Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His 35 40 45

Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val 50 55 60

Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg 65 70 75 80

Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr 85 90 95

Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu

100 105 110

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

115 120 125

Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly

130 135 140

Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln 145 150 155 160

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

- 416 046596

165 170 175

Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn

180 185 190

Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His

195 200 205

Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala 210 215 220

Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe 225 230 235 240

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

245 250 255

Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu

260 265 270

Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu

275 280 285

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

290 295 300

Ile Phe Leu Pro Pro Leu Gln Gly Asp Phe Gly Ala Phe Ser Ala Phe 305 310 315 320

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

325 330 335

Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu

340 345 350

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

355 360 365

Phe Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Leu Gln Gly Tyr

370 375 380

His Phe Thr Ala Asp Ser Trp Glu His Ile His Phe Ile Gly Lys Ile

385 390 395 400

Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr 405 410 415

- 417 046596

Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser

420 425 430

Thr <210> 240 <211> 1299 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 240 gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60 gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120 ga aaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180 agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240 gccagggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300 gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360 gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420 caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480 aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540 gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600 aaggactaca tacac ccacagcttt ctgtgctacg gaaaggacca ggctctgtgg 660 cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720 caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780 agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840 cagtgccacc agagcatcct ggaactgt tc aacaccagct actgccccta cagccagtgc 900 gccttcaacg gcatcttcct gccacctctg caggggggatt tcggcgcctt cagcgccttc 960 tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020 gagatgatga agaagtt ctg cgcccaaccc tgggaggaaa tcaagacctc ctacgctggc 1080 gtgaacgaga agtacctgag cgagttttgc ttcagcggca cctacatcct gagcctgctg 1140 ctgcagggct accacttcac cgccgatagc tgggagcaca tccacttcat cggcaagatt 1200 cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260 gccgagcagc ccctgagcac acctctgagc acc 1299

- 418 046596 <210> 241 <211> 442 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 241

Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Thr Ser Ser Thr 1 5 10 15

Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly Ile Val Leu Asp 20 25 30

Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys Trp Pro Ala Glu 35 40 45

Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu Glu Cys Arg Val 50 55 60

Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val Asn Glu Ile Gly 65 70 75 80

Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu Val Ile Pro Arg 85 90 95

Ser Gln His Gln Glu Thr Pro Val Tyr Leu Gly Ala Thr Ala Gly Met

100 105 110

Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp Arg Val Leu Asp

115 120 125

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

130 135 140

Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly Trp Ile Thr Ile 145 150 155 160

Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln Glu Thr Phe Gly

165 170 175

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

180 185 190

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

195 200 205

- 419 046596

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

210 215 220

Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile Gln Val Ala Ser

225 230 235 240

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

245 250 255

Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr Lys Arg Phe Glu

260 265 270

Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly Ile Gly Asn Tyr

275 280 285

Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn Thr Ser Tyr Cys

290 295 300

Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu Pro Pro Leu Gln

305 310 315 320

Gly Asp Phe Gly Ala Phe Ser Ala Phe Tyr Phe Val Met Lys Phe Leu

325 330 335

Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val Thr Glu Met Met

340 345 350

Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys Thr Ser Tyr Ala

355 360 365

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

370 375 380

Ile Leu Ser Leu Leu Leu Gln Gly Tyr His Phe Thr Ala Asp Ser Trp

385 390 395 400

Glu His Ile His Phe Ile Gly Lys Ile Gln Gly Ser Asp Ala Gly Trp

405 410 415

Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile Pro Ala Glu Gln

420 425 430

Pro Leu Ser Thr Pro Leu Ser His Ser Thr

435 440

- 420 046596 <210> 242 <211> 1326 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 242 gcccctacca gcagcagcac caagaaaacc cagctgacca gcagcaccca gaacaaggcc 60 ctgcccgaga acgtgaagta cggcatcgtg ctggatgccg gcagcagcca caccagcctg 120 tacatcta ca agtggcctgc cgagaaagaa aacgacaccg gcgtggtgca tcaggtggaa 180 gagtgcagag tgaagggccc tggcatcagc aagttcgtgc agaaagtgaa cgagatcggc 240 atctacctga ccgactgcat ggaacgggcc agggaagtga tccccagaag ccagcaccag 300 gaaacccccg tgtatctggg agccaccgcc ggcatgagac tgctgagaat ggaaagcgag 360 gaactggccg accgggtgct ggacgtggtg gaaagaagcc tgagcaacta cccattcgat 420 tttcaaggcg cca gaatcat caccggccag gaagaaggcg cctacggctg gatcaccatc 480 aactacctgc tgggcaagtt cagccagaag aatcaggaaa ccttcggcgc cctggacctg 540 ggcggagctt ctacccaagt gaccttcgtg ccccagaatc agaccatcga gagccccgac 600 agttccggct gtacggcaag gactacaatg tgtacaccca cagctttctg 660 tgctacggaa aggaccaggc tctgtggcag aagctggcca aggacatcca ggtggccagc 720 aacgagatcc tgcgggaccc ttgcttccac cccggctaca agaaagtcgt gaacgtgtcc 780 gacctgtaca agaccccctg caccaagaga ttcgagatga ccctgccctt ccagcagttc 840 gagatccagg gcatcggcaa ttacc agcag tgccaccaga gcatcctgga actgttcaac 900 accagctact gcccctacag ccagtgcgcc ttcaacggca tcttcctgcc acctctgcag 960 ggggatttcg gcgccttcag cgccttctac ttcgtgatga agttcctgaa cctgaccagc 1020 gagaaggtgt c caggaaaa agtgacagag atgatgaaga agttctgcgc ccaaccctgg 1080 gaggaaatca agacctccta cgctggcgtg aacgagaagt acctgagcga gttttgcttc 1140 agcggcacct acatcctgag cctgctgctg cagggctacc acttcaccgc cgatagctgg 1200 gagcacatcc acttcatcgg caagattcag ggcagcgacg ccggctggac actgggctac 1260 atgctgaatc tgaccaacat gatccccgcc gagcagcc cc tgagcacacc tctgagccac 1320 agcacc 1326 <210> 243 <211> 430 <212> PROTEIN <213> Artificial sequence

- 421 046596 <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 243

Ala Pro Thr Thr Gln Asn Lys Ala Leu Pro Glu Asn Val Lys Tyr Gly 1 5 10 15

Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr Ile Tyr Lys 20 25 30

Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His Gln Val Glu 35 40 45

Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val Gln Lys Val 50 55 60

Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg Ala Arg Glu 65 70 75 80

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

90 95

Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu Leu Ala Asp

100 105 110

Arg Val Leu Asp Val Val Glu Arg Ser Leu Ser Asn Tyr Pro Phe Asp

115 120 125

Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly Ala Tyr Gly

130 135 140

Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln Lys Asn Gln 145 150 155 160

Glu Thr Phe Gly Ala Leu Asp Leu Gly Gly Ala Ser Thr Gln Val Thr

165 170 175

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

180 185 190

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

195 200 205

Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala Lys Asp Ile

210 215 220

Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe His Pro Gly

- 422 046596

225 230 235 240

Tyr Lys Lys Val Val Asn Val Ser Asp Leu Tyr Lys Thr Pro Cys Thr

245 250 255

Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu Ile Gln Gly

260 265 270

Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu Leu Phe Asn

275 280 285

Thr Ser Tyr Cys Pro Tyr Ser Gln Cys Ala Phe Asn Gly Ile Phe Leu

290 295 300

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

305 310 315 320

Met Lys Phe Leu Asn Leu Thr Ser Glu Lys Val Ser Gln Glu Lys Val

325 330 335

Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu Glu Ile Lys

340 345 350

Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu Tyr Cys Phe

355 360 365

Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr His Phe Thr

370 375 380

Ala Asp Ser Trp Glu Asp Ile His Phe Ile Gly Lys Ile Gln Gly Ser 385 390 395 400

Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr Asn Met Ile

405 410 415

Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser Thr

420 425 430 <210> 244 <211> 1290 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 244 gcccctacca cccagaacaa ggccctgccc gagaacgtga agtacggcat cgtgctggat 60

- 423 046596 gccggcagca gccacaccag cctgtacatc tacaagtggc ctgccgagaa agaaaacgac 120 accggcgtgg tgcatcaggt ggaagagtgc agagtgaagg gccctggcat cagcaagttc 180 gtgcagaaag tgaacgagat cggcatctac ctgaccgact gcat ggaacg ggccagggaa 240 gtgatcccca gaagccagca ccaggaaacc cccgtgtatc tgggagccac cgccggcatg 300 agactgctga gaatggaaag cgaggaactg gccgaccggg tgctggacgt ggtggaaaga 360 agcctgagca actacccatt cgattttcaa ggcgccagaa tcatcaccgg ccadgaagaa 420 ggcgcctacg gctggatcac catcaactac ctgctgggca agttcagcca gaagaatcag 480 gaaaccttcg gcgccctgga cctgggcgga gcttctaccc aagtgacctt cgtgccccag 540 aatcagacca tcgagagccc cgacaacgcc ctgcagttcc ggctgtacgg caaggactac 600 aatgtgtaca cccacagctt tctgtgctac ggaaagg acc aggctctgtg gcagaagctg 660 gccaaggaca tccaggtggc cagcaacgag atcctgcggg acccttgctt ccaccccggc 720 tacaagaaag tcgtgaacgt gtccgacctg tacaagaccc cctgcaccaa gagattcgag 780 atgaccctgc ccttccagca gttcgagatc cagg gcatcg gcaattacca gcagtgccac 840 cagagcatcc tggaactgtt caacaccagc tactgcccct acagccagtg cgccttcaac 900 ggcatcttcc tgccacctct gcagggggat ttcggcgcct tcagcgcctt ctacttcgtg 960 atgaagttcc tgaacctgac cagcgagaag gtgtcccagg aaaaagtgac agagatgatg 1020 aagaagttct gcgcccagcc ctgggaggaa atcaagacct gctgg cgtgaaagag 1080 aagtacctga gcgagtactg cttcagcggc acctacatcc tgagcctgct gcagcagggc 1140 taccacttca ccgccgatag ctgggaggac atccacttca tcggcaagat tcaggcagc 1200 gacgccggct ggacactggg ctacatgctg aatctgacca a catgatccc cgccgagcag 1260 cccctgagca cacctctgag ccacagcacc 1290 <210> 245 <211>433 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polypeptide <400> 245

Ala Pro Thr Ser Ser Ser Thr Gln Asn Lys Ala Leu Pro Glu Asn Val 1 5 10 15

Lys Tyr Gly Ile Val Leu Asp Ala Gly Ser Ser His Thr Ser Leu Tyr

25 30

- 424 046596

Ile Tyr Lys Trp Pro Ala Glu Lys Glu Asn Asp Thr Gly Val Val His 35 40 45

Gln Val Glu Glu Cys Arg Val Lys Gly Pro Gly Ile Ser Lys Phe Val 50 55 60

Gln Lys Val Asn Glu Ile Gly Ile Tyr Leu Thr Asp Cys Met Glu Arg 65 70 75 80

Ala Arg Glu Val Ile Pro Arg Ser Gln His Gln Glu Thr Pro Val Tyr 85 90 95

Leu Gly Ala Thr Ala Gly Met Arg Leu Leu Arg Met Glu Ser Glu Glu

100 105 110

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

115 120 125

Pro Phe Asp Phe Gln Gly Ala Arg Ile Ile Thr Gly Gln Glu Glu Gly

130 135 140

Ala Tyr Gly Trp Ile Thr Ile Asn Tyr Leu Leu Gly Lys Phe Ser Gln 145 150 155 160

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

165 170 175

Gln Val Thr Phe Val Pro Gln Asn Gln Thr Ile Glu Ser Pro Asp Asn

180 185 190

Ala Leu Gln Phe Arg Leu Tyr Gly Lys Asp Tyr Asn Val Tyr Thr His

195 200 205

Ser Phe Leu Cys Tyr Gly Lys Asp Gln Ala Leu Trp Gln Lys Leu Ala 210 215 220

Lys Asp Ile Gln Val Ala Ser Asn Glu Ile Leu Arg Asp Pro Cys Phe 225 230 235 240

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

245 250 255

Pro Cys Thr Lys Arg Phe Glu Met Thr Leu Pro Phe Gln Gln Phe Glu

260 265 270

Ile Gln Gly Ile Gly Asn Tyr Gln Gln Cys His Gln Ser Ile Leu Glu

275 280 285

- 425 046596

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

290 295 300

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

305 310 315 320

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

325 330 335

Glu Lys Val Thr Glu Met Met Lys Lys Phe Cys Ala Gln Pro Trp Glu

340 345 350

Glu Ile Lys Thr Ser Tyr Ala Gly Val Lys Glu Lys Tyr Leu Ser Glu

355 360 365

Tyr Cys Phe Ser Gly Thr Tyr Ile Leu Ser Leu Leu Gln Gln Gly Tyr

370 375 380

His Phe Thr Ala Asp Ser Trp Glu Asp Ile His Phe Ile Gly Lys Ile

385 390 395 400

Gln Gly Ser Asp Ala Gly Trp Thr Leu Gly Tyr Met Leu Asn Leu Thr

405 410 415

Asn Met Ile Pro Ala Glu Gln Pro Leu Ser Thr Pro Leu Ser His Ser

420 425 430

Thr <210> 246 <211> 1299 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic polynucleotide <400> 246 gcccctacca gcagcagcac ccagaacaag gccctgcccg agaacgtgaa gtacggcatc 60 gtgctggatg ccggcagcag ccacaccagc ctgtacatct acaagtggcc tgccgagaaa 120 ga aaacgaca ccggcgtggt gcatcaggtg gaagagtgca gagtgaaggg ccctggcatc 180 agcaagttcg tgcagaaagt gaacgagatc ggcatctacc tgaccgactg catggaacgg 240 gccagggaag tgatccccag aagccagcac caggaaaccc ccgtgtatct gggagccacc 300

- 426 046596 gccggcatga gactgctgag aatggaaagc gaggaactgg ccgaccgggt gctggacgtg 360 gtggaaagaa gcctgagcaa ctacccattc gattttcaag gcgccagaat catcaccggc 420 caggaagaag gcgcctacgg ctggatcacc atcaactacc tgctgggcaa gttcagccag 480 aagaatcagg aaaccttcgg cgccctggac ctgggcggag cttctaccca agtgaccttc 540 gtgccccaga atcagaccat cgagagcccc gacaacgccc tgcagttccg gctgtacggc 600 aaggactaca atgtgtacac ccacagcttt ctgtgctac g gaaaggacca ggctctgtgg 660 cagaagctgg ccaaggacat ccaggtggcc agcaacgaga tcctgcggga cccttgcttc 720 caccccggct acaagaaagt cgtgaacgtg tccgacctgt acaagacccc ctgcaccaag 780 agattcgaga tgaccctgcc cttccagcag ttcgagatcc agggcatcgg caattaccag 840 cagtgccacc agagcatcct ggaactgttc aacaccagct actgccccta ca gccagtgc 900 gccttcaacg gcatcttcct gccacctctg caggggggatt tcggcgcctt cagcgccttc 960 tacttcgtga tgaagttcct gaacctgacc agcgagaagg tgtcccagga aaaagtgaca 1020 gagatgatga agaagttctg cgcccagccc tgggagg aaa tcaagacctc ctacgctggc 1080 gtgaaagaga agtacctgag cgagtactgc ttcagcggca cctacatcct gagcctgctg 1140 cagcagggct accacttcac cgccgatagc tgggaggaca tccacttcat cggcaagatt 1200 cagggcagcg acgccggctg gacactgggc tacatgctga atctgaccaa catgatcccc 1260 gccgagcagc ccctgagcac acctctgagc cacagcacc 1299 <210> 7 <211> 6 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 247

Glu Phe Arg His Asp Ser 1 5 <210> 248 <211> 18 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic oligonucleotide <400> 248 gaattccggc acgacagc 18

- 427 046596 <210> 249 <211>6 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic 6xHis tag <400> 249

His His His His His His 1 5 <210> 250 <211> 18 <212> DNA <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: Synthetic oligonucleotide <400> 250 catcatcatc atcatcac 18 <210> 251 <211> 5 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 251

Gly Gly Gly Gly Ser 1 5 <210> 252 <211> 8 <212> PROTEIN <213> Artificial sequence <220>

<221> source <223> /note=Description of artificial sequence: synthetic peptide <400> 252

Val Lys Glu Lys Tyr Leu Ser Glu 1 5 <210> 253 <211>7 <212> PROTEIN <213> Artificial sequence <220>

<221> source

- 428 046596 <223> /note=Description of artificial sequence: synthetic peptide <400> 253

Gln Glu Arg Trp Leu Arg Asp 1 5

Claims (16)

1. Solubilized human apyrase containing modifications: N-terminal deletion, C-terminal deletion and modification of the central region, where a) the length of the N-terminal deletion is from 30 to 50 amino acids, b) the length of the C-terminal deletion is from 20 to 40 amino acids, and c) the modification of the central region includes a deletion of 10 to 15 contiguous amino acids, wherein the deletion is a deletion of amino acids 193 to 204 relative to the wild type CD39 sequence of SEQ ID NO: 1, and wherein the modification of the central region includes itself a point mutation comprising one, two, three, four or five point mutations relative to the wild type CD39 sequence according to SEQ ID NO: 1, selected from the group consisting of K71E, N73Q, V95A, G102D, Y104S, T106S, R113M, L149M, V151A, E173D, T229A, L254M, K258R, W263R, E276D, N292Q, R304G, I319T, N327Q, A362N, F365S, N371Q, K405N, Y412F, L424Q, H436D, I437N, 9S, G441D, N457Q, P463S and S469R. 2. The solubilized human apyrase according to claim 1, containing a sequence selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 32, SEQ ID NO: 54, SEQ ID NO: 56, SEQ ID NO: 70, SEQ ID NO: 76 and SEQ ID NO: 78. 3. The solubilized human apyrase of any one of the preceding claims, comprising a sequence selected from the group consisting of SEQ ID NO: 131, SEQ ID NO: 133, SEQ ID NO: 135, SEQ ID NO: 137, SEQ ID NO: 139 and SEQ ID NO: 141. 4. The solubilized human apyrase according to claim 3, comprising or consisting of a sequence selected from the group consisting of SEQ ID NO: 213, SEQ ID NO: 227, SEQ ID NO: 219, SEQ ID NO: 225, SEQ ID NO: 217, SEQ ID NO: 209, SEQ ID NO: 221, SEQ ID NO: 72, SEQ ID NO: 215, SEQ ID NO: 223, SEQ ID NO: 211, SEQ ID NO: 58 and SEQ ID NO: 229. 5. The solubilized human apyrase according to claim 4, consisting of a sequence selected from the group consisting of SEQ ID NO: 58, SEQ ID NO: 72 and SEQ ID NO: 229. 6. A pharmaceutical composition containing a therapeutically effective dose of apyrase according to any one of claims 1 to 5 and one or more pharmaceutically acceptable carriers. 7. The pharmaceutical composition according to claim 6, further containing one or more additional active ingredients. 8. Use of isolated apyrase according to claims 1-5 for the treatment of tissue damage. 9. Use of the isolated apyrase according to claim 8, wherein the tissue damage is acute brain injury (stroke); acute multiple organ failure; delayed graft function after kidney or other solid organ transplantation; burn; radiation injury; acute injury due to trauma and/or hypoxia, such as acute respiratory distress syndrome (ARDS) or lung injury; acute kidney injury, such as acute kidney injury due to chest surgery (eg, aortic valve replacement, coronary artery bypass grafting), or sepsis, or rhabdomyolysis, or the toxic effects of antibiotics or other drugs; acute myocardial injury. 10. Use of isolated apyrase according to claims 1-5 for the treatment of acute kidney injury associated with cardiac surgery. 11. Use of isolated apyrase according to claims 1 to 5 for the treatment of delayed graft function (DGF), acute respiratory distress syndrome (ARDS), acute myocardial infarction (AMI), traumatic brain injury (TB1)/acute ischemic stroke (AIS) , ischemia-reperfusion injury (IRI), or combinations thereof, often called multiple organ failure (MOF) forms. 12. Use of isolated apyrase according to claims 1-5 for the treatment of acute kidney injury associated with sepsis. 13. An isolated nucleic acid molecule encoding any apyrase according to claims 1-5. 14. A cloning or expression vector containing one or more nucleic acid sequences according to claim 13, where the vector is suitable for recombinant production of the isolated apyrase according to claims 1-5. - 429 046596 15. A host cell containing one or more cloning or expression vectors according to claim 14. 16. A method for producing apyrase according to any one of claims 1 to 5, including culturing a host cell according to claim 15, purifying and extracting said apyrase.