一种新型冠状病毒SARS-CoV-2中和性抗体及应用

Novel coronavirus SARS-CoV-2 neutralizing antibody and application thereof

文档序号：2604 发布日期：2021-09-17 浏览：50次中文

1. An antibody capable of binding to the RBD region in the S1 subunit of Spike protein of the novel coronavirus SARS-CoV-2, thereby blocking the binding activity of the host cell membrane surface receptor ACE2 to the Spike protein.

2. An antibody according to claim 1, wherein said antibody is a neutralizing fully human antibody.

3. An antibody according to claim 1, wherein said antibody comprises a heavy chain VH and a light chain VL, each of said VH and VL comprising the variable regions CDR1, CDR2 and CDR 3; wherein the content of the first and second substances,

the amino acid sequence of CDR1 of VH is selected from one of SEQ ID NO.63-SEQ ID NO.76, SEQ ID NO.303-SEQ ID NO. 305;

and/or the amino acid sequence of CDR2 of said VH is selected from one of SEQ ID NO.77-SEQ ID NO.86, SEQ ID NO.306-SEQ ID NO. 308;

and/or the amino acid sequence of CDR3 of VH is selected from one of SEQ ID NO.87-SEQ ID NO.104, SEQ ID NO.309-SEQ ID NO. 312;

and/or the amino acid sequence of the CDR1 of the VL is selected from one of SEQ ID NO.105-SEQ ID NO.119, SEQ ID NO.313-SEQ ID NO. 315;

and/or the amino acid sequence of the CDR2 of the VL is selected from one of SEQ ID NO.120-SEQ ID NO.126 and SEQ ID NO. 316;

and/or the amino acid sequence of the CDR3 of the VL is selected from one of SEQ ID NO.127-SEQ ID NO.152, SEQ ID NO.317-SEQ ID NO. 327.

4. The antibody of claim 1, wherein the VH of said antibody has an amino acid sequence selected from the group consisting of SEQ ID No.1-SEQ ID No.30, SEQ ID No.279-SEQ ID No. 289; and/or the amino acid sequence of the VL of the antibody is selected from one of SEQ ID NO.31-SEQ ID NO.62, SEQ ID NO.290-SEQ ID NO. 302.

5. An antibody derived from the antibody according to any one of claims 1 to 4, wherein the derived antibody is selected from one of the following (1) to (4):

(1) a single chain antibody obtained by linking VH and VL of an antibody according to any one of claims 1 to 4;

(2) a fusion antibody comprising the single-chain antibody of (1);

(3) a Fab comprising the VH and VL of the antibody of any one of claims 1 to 4;

(4) an intact antibody comprising the VH and VL of an antibody of any one of claims 1-4.

6. The derivatized antibody of claim 5, wherein the derivatized antibody is an scFv single chain antibody having an amino acid sequence selected from the group consisting of SEQ ID No.215-SEQ ID No.246, SEQ ID No.356-SEQ ID No. 368.

7. The derivatized antibody of claim 5, wherein the derivatized antibody is a whole IgG antibody; wherein the preparation steps of the complete IgG antibody comprise: the gene segments encoding the VH and VL were subcloned into human IgG1 CH vector and light chain CL expression vector, transfected into cells for expression and affinity purified, respectively.

8. A biomaterial related to the antibody according to any one of claims 1 to 4, wherein the biomaterial is one selected from the group consisting of the following (A) to (B):

(A) a nucleic acid molecule encoding an antibody according to any one of claims 1 to 4 and/or a nucleic acid molecule encoding a derivatized antibody according to any one of claims 5 to 7;

(B) an expression cassette, a recombinant vector, a recombinant microorganism, a recombinant cell line comprising the nucleic acid molecule of (A).

9. Biomaterial according to claim 8, characterized in that the sequence of the nucleic acid encoding said VH is selected from one of SEQ ID No.153 to SEQ ID No.182, SEQ ID No.328 to SEQ ID No. 342; and/or, the sequence of the nucleic acid encoding the VL is selected from one of SEQ ID NO.183-SEQ ID NO.214, SEQ ID NO.343-SEQ ID NO. 355; and/or the sequence of the nucleic acid for encoding the scFv single-chain antibody is selected from one of SEQ ID NO.247-SEQ ID NO.278 and SEQ ID NO.369-SEQ ID NO. 381.

10. An affinity matured antibody obtained by affinity maturation of an antibody according to any one of claims 1 to 4.

11. The affinity matured antibody of claim 10, wherein the amino acid sequence of VH CDR1 of the affinity matured antibody is SEQ ID No.64 or SEQ ID No.69, the amino acid sequence of VH CDR2 is SEQ ID No.77, SEQ ID No.382 or SEQ ID No.383, the amino acid sequence of VH CDR3 is SEQ ID No.88 or SEQ ID No. 95; the amino acid sequence of VL CDR1 of the affinity matured antibody is SEQ ID NO.106 or SEQ ID NO.107, the amino acid sequence of VL CDR2 is SEQ ID NO.120 or SEQ ID NO.123, and the amino acid sequence of VL CDR3 is one of SEQ ID NO.129 or SEQ ID NO.392-SEQ ID NO. 396.

12. The affinity matured antibody of claim 10, wherein the amino acid sequence of the VH of the affinity matured antibody is selected from one of SEQ ID No.384 to SEQ ID No. 387; the amino acid sequence of VL of the affinity matured antibody is selected from one of SEQ ID NO.397-SEQ ID NO. 402.

13. The affinity matured antibody of claim 12, wherein the nucleic acid encoding said VH has a sequence selected from one of SEQ ID No.388 to SEQ ID No. 391; the sequence of the nucleic acid for encoding the VL is selected from one of SEQ ID NO.403-SEQ ID NO. 408.

14. Use of an antibody according to any one of claims 1 to 4, a derivatized antibody according to any one of claims 5 to 7, a biological material according to claim 8 or 9, or an affinity matured antibody according to any one of claims 10 to 13 for the preparation of a product for the treatment and/or prevention of the novel coronavirus SARS-CoV-2 and diseases caused thereby.

15. A method for producing an antibody according to any one of claims 1 to 4, comprising the steps of:

step 1) establishing a fully humanized phage antibody library by using peripheral blood of a patient in a rehabilitation period infected by the novel coronavirus; step 2) carrying out panning on the fully human phage antibody library constructed in the step 1) by using biotinylated Spike1-RBD protein to obtain potential antibodies with RBD binding activity;

step 3) screening antibodies with potential neutralizing activity by analyzing the potential antibodies obtained in step 2) at the cell and protein level to block the binding activity of ACE2 and Spike protein.

Background

The mean incubation period of the pneumonia of the novel coronavirus (SARS-CoV-2) is 3-7 days, and the symptoms of the infected upper respiratory tract are not prominent. Part of patients infected by the novel coronavirus only show low fever, slight weakness and the like, and do not have the pulmonary inflammation. But can present as middle-low fever even without obvious fever in the course of disease of heavy and critical patients. These non-specific clinical manifestations present even greater challenges to epidemic prevention and control. Effective vaccines and therapeutic drugs play a critical role in controlling viral transmission and improving patient prognosis. However, until now, there is no relevant vaccine against coronaviruses. In the aspect of drug therapy, broad-spectrum interferon and lopinavir/ritonavir are mainly adopted for antiviral treatment aiming at novel coronavirus infection, the curative effect is not obvious, and no specific antiviral drug exists, so that a corresponding therapeutic drug is urgently developed.

The neutralizing antibody can be used for specifically and effectively preventing and treating the virus infection. However, the availability of human plasma and/or immunoglobulins with high affinity against pathogens requires a large donation by convalescent patients and presents other potential infection risks, thereby limiting the widespread use of these human-derived products. With the research on coronaviruses, it is now clearly known that the Spike protein on the surface of coronaviruses plays a key role in the invasion of viruses into hosts, and a Receptor Binding Domain (RBD) binding to the cell surface of a host exists in the S1 subunit of the protein, which is responsible for recognizing cellular receptors. Thus, an antibody that specifically binds to the RBD region will have good virus neutralization. As can be seen by aligning the sequence of the Spike protein RBD of SARS-CoV-2, SARS-CoV and MERS-CoV, the sequence similarity of SARS-CoV-2 and SARS-CoV in RBD region is 73.5%. SARS-CoV can enter into cells by binding with host cell membrane surface receptor ACE2 via the region, so as similar to SARS-CoV, antibody against SARS-CoV-2RBD region of novel coronavirus can be developed or virus can be neutralized. It was shown that, unlike SARS-CoV, several critical amino acids in the RBD region of the Spike protein of the novel SARS-CoV-2 coronavirus, which bind to ACE2, are mutated, and that neutralizing antibodies against SARS-CoV, which have been developed in the past, may not have a neutralizing effect on the virus. Thus, there is a need to develop new neutralizing antibodies against SARS-CoV-2 novel coronavirus.

Disclosure of Invention

In order to overcome the defects in the prior art, the invention provides a novel coronavirus SARS-CoV-2 neutralizing antibody and a preparation method and application thereof.

In order to achieve the purpose, the invention adopts the following technical scheme:

the first aspect of the present invention provides an antibody capable of binding to the RBD region in the S1 subunit of Spike protein of the novel coronavirus SARS-CoV-2, thereby blocking the binding activity of ACE2, a host cell membrane surface receptor, to the Spike protein.

In order to further optimize the technical scheme, the technical measures adopted by the invention also comprise:

further, the antibody is a neutralizing fully human antibody.

Further, the antibody comprises a heavy chain VH and a light chain VL, each comprising the variable regions CDR1, CDR2, and CDR 3; wherein the content of the first and second substances,

the amino acid sequence of CDR1 of VH is selected from one of SEQ ID NO.63-SEQ ID NO.76, SEQ ID NO.303-SEQ ID NO. 305;

and/or the amino acid sequence of CDR2 of said VH is selected from one of SEQ ID NO.77-SEQ ID NO.86, SEQ ID NO.306-SEQ ID NO. 308;

and/or the amino acid sequence of the CDR3 of the VH is selected from one of SEQ ID NO.87-SEQ ID number 104, SEQ ID NO.309-SEQ ID NO. 312;

and/or the amino acid sequence of the CDR1 of the VL is selected from one of SEQ ID NO.105-SEQ ID number 119, SEQ ID NO.313-SEQ ID NO. 315;

and/or the amino acid sequence of the CDR2 of the VL is selected from one of SEQ ID NO.120-SEQ ID number 126 and SEQ ID NO. 316;

and/or the amino acid sequence of the CDR3 of the VL is selected from one of SEQ ID NO.127-SEQ ID number 152, SEQ ID NO.317-SEQ ID NO. 327.

Further, the amino acid sequence of the VH of the antibody is selected from one of SEQ ID NO.1-SEQ ID number 30, SEQ ID NO.279-SEQ ID NO. 289; and/or the amino acid sequence of the VL of the antibody is selected from one of SEQ ID NO.31-SEQ ID NO.62, SEQ ID NO.290-SEQ ID NO. 302.

Still further, the amino acid sequence of VH of the antibody is selected from one of SEQ ID NO.2-SEQ ID number 4, SEQ ID NO. 14; and/or the amino acid sequence of the VL of the antibody is selected from one of SEQ ID NO.32-SEQ ID NO.34 and SEQ ID NO. 44.

In a second aspect of the present invention, there is provided an antibody derived from any one of the above antibodies, which is selected from one of the following (1) to (4):

(1) a single-chain antibody obtained by linking VH and VL of any of the above-mentioned antibodies;

(2) a fusion antibody comprising the single-chain antibody of (1);

(3) a Fab comprising the VH and VL of any of the above antibodies;

(4) an intact antibody comprising the VH and VL of any one of the above antibodies.

Further, the derivative antibody is an scFv single-chain antibody, and the amino acid sequence of the scFv single-chain antibody is selected from one of SEQ ID NO.215-SEQ ID NO.246, and SEQ ID NO.356-SEQ ID NO. 368.

Further, the amino acid sequence of the scFv single-chain antibody is one of SEQ ID NO.216-SEQ ID NO.218 and SEQ ID NO. 228. More specifically, the scFv single-chain antibodies are HTS0422, HTS0433, HTS0446 and HTS0483 in table 1 below, and the sequences of their heavy chains, light chains and their variable regions are also shown in table 1.

It is understood that the scFv single-chain antibody is a fully human antibody and can be directly developed into an antibody drug for human use. Constructing and expressing the gene encoding the human scFv antibody to obtain various small molecular genetic engineering antibodies, such as Fab antibody, F (ab)₂Single-chain antibody, nano-antibody, antibody fusion protein, IgG whole antibody and the like.

Further, the derivative antibody is a whole IgG antibody; wherein the preparation steps of the complete IgG antibody comprise: the gene segments encoding the VH and VL are subcloned into human IgG1 CH vector and light chain CL expression vector, transfected into cells for expression and affinity purified. Furthermore, the human IgG1 CH vector was pTT5-hIgG1, the light chain CL expression vector was pTT5-hKappa, and the transfected cells were 293F cells, which were affinity purified using protein G.

The third aspect of the present invention provides a biomaterial related to any one of the above antibodies, which is selected from one of the following (a) to (B):

(A) a nucleic acid molecule encoding any one of the above antibodies or derivative antibodies;

(B) an expression cassette, a recombinant vector, a recombinant microorganism, a recombinant cell line comprising the nucleic acid molecule of (A).

It is understood that expression cassettes, recombinant vectors, recombinant microorganisms, recombinant cell lines can be prepared using methods conventional in the art.

Further, in the above biomaterial, the sequence of the nucleic acid encoding the VH is selected from one of SEQ ID No.153 to SEQ ID No.182, SEQ ID No.328 to SEQ ID No. 342; and/or, the sequence of the nucleic acid encoding the VL is selected from one of SEQ ID NO.183-SEQ ID NO.214, SEQ ID NO.343-SEQ ID NO. 355; and/or the sequence of the nucleic acid for encoding the scFv single-chain antibody is selected from one of SEQ ID NO.247-SEQ ID NO.278 and SEQ ID NO.369-SEQ ID NO. 381.

Still further, in the above-mentioned biomaterial, the sequence of the nucleic acid encoding said VH is selected from one of SEQ ID No.154 to SEQ ID No.156, SEQ ID No. 166; and/or, the sequence of the nucleic acid encoding the VL is selected from one of SEQ ID NO.184-SEQ ID NO.186, SEQ ID NO. 196; and/or the sequence of the nucleic acid for encoding the scFv single-chain antibody is selected from one of SEQ ID NO.248-SEQ ID number 250 and SEQ ID NO. 260.

The nucleotide sequence of the above-described antibody or derived antibody can be readily mutated by those skilled in the art using known methods, such as directed evolution and point mutation. The nucleotide which is artificially modified and has 75% or more identity to the nucleotide sequence of the antibody or the derivative antibody of the present invention is a nucleotide sequence derived from the nucleotide sequence of the present invention and equivalent to the sequence of the present invention as long as the nucleotide encodes the antibody or the derivative antibody and has the activity of the antibody or the derivative antibody.

Further, the number of the scFv single chain antibody is 45, wherein, an antibody heavy chain is represented by VH, and a heavy chain variable region is represented by VH CDR1, VH CDR2 and VH CDR 3; the antibody light chain is represented by VL, wherein the light chain variable regions are represented by VL CDR1, VL CDR2, and VL CDR3, and the variable region gene sequences of the antibody heavy chain and the antibody light chain were studied for Germline gene segments, respectively represented by VH _ Germline and VL Germline.

The related sequences of the 45 scFv single chain antibodies are shown in Table 1 below:

TABLE 1 related sequences of scFv Single chain antibodies

In a fourth aspect of the invention, there is provided an affinity matured antibody obtained from any one of the antibodies described above after affinity maturation.

Further, the amino acid sequence of VH CDR1 of the affinity matured antibody is SEQ ID NO.64 or SEQ ID NO.69, the amino acid sequence of VH CDR2 is SEQ ID NO.77, SEQ ID NO.382 or SEQ ID NO.383, and the amino acid sequence of VH CDR3 is SEQ ID NO.88 or SEQ ID NO. 95; the amino acid sequence of VL CDR1 of the affinity matured antibody is SEQ ID NO.106 or SEQ ID number 107, the amino acid sequence of VL CDR2 is SEQ ID NO.120 or SEQ ID NO.123, and the amino acid sequence of VL CDR3 is one of SEQ ID NO.129 or SEQ ID NO.392-SEQ ID NO. 396.

Further, the amino acid sequence of the VH of the affinity matured antibody is selected from one of SEQ ID NO.384-SEQ ID NO. 387; the amino acid sequence of VL of the affinity matured antibody is selected from one of SEQ ID NO. 397-402.

Further, the sequence of the nucleic acid encoding the affinity matured antibody VH is selected from one of SEQ ID NO.388-SEQ ID NO. 391; the sequence of the nucleic acid for encoding the VL of the affinity matured antibody is selected from one of SEQ ID NO.403-SEQ ID NO. 408.

Further, the preparation step of the affinity matured antibody comprises:

designing a point mutation primer, and designing NNS (N represents any base, and S represents base C or G) aiming at the CDR region of any antibody;

performing PCR reaction according to the mutation primer designed in the step (1) to circularly batch plasmids;

step (3) carrying out plasmid recovery on the PCR reaction product in the step (2), and carrying out transformation and plasmid preparation on the PCR product;

step (4) carrying out scFv blocking activity detection on each site-directed mutated clone induced expression scFv;

and (5) performing single cloning on the mutation with high affinity, and identifying and sequencing to obtain the mature antibody with affinity.

Further, the PCR reaction system and the reaction conditions thereof are as follows:

	volume (uL)
		Fn-primer(2μM)	5
Rn-primer(2μM)	5
		Template plasmid (100ng/uL)	1
PrimerSRAR Max Premix	5
		Water (W)	34
Total volume	50

Wherein, Fn and Rn are based on the sequence of light chain and heavy chain CDR1, CDR2 and CDR3 regions, only mutation is carried out on a single site in the CDR region each time, the base of the site is represented by NNS, the forward primer is sequentially named as F1-primer, F2-primer … … Fn-primer, and the reverse primer is sequentially named as R1-primer and R2-primer … … Rn-primer;

reaction conditions are as follows: denaturation at 95 deg.C for 5 min; 30S at 95 ℃, 30S at 58 ℃ and 4min at 72 ℃; 10min at 72 ℃.

Further, affinity maturation was performed on HTS0422, HTS0433, HTS0446, HTS0483 in table 1 above; HTS0433 and HTS0483 were affinity matured more specifically, and the sequence information of the antibody after affinity maturation is shown in table 2 below:

TABLE 2 affinity matured antibody sequences

The fifth aspect of the invention provides a product for treating and/or preventing the novel coronavirus SARS-CoV-2 and diseases caused by the coronavirus SARS-CoV-2, wherein the active ingredient of the product is any one of the above-mentioned antibody, derivative antibody, biological material or affinity matured antibody.

The sixth aspect of the invention provides an application of any one of the above antibodies, derivative antibodies, biological materials or affinity matured antibodies in preparing products for treating and/or preventing novel coronavirus SARS-CoV-2 and diseases caused by the coronavirus SARS-CoV-2.

Further, the product may be a diagnostic agent, a therapeutic drug, a vaccine, or the like.

The seventh aspect of the present invention provides a method for producing any one of the above antibodies, which comprises the steps of:

step 1) establishing a fully humanized phage antibody library by using peripheral blood of a patient in a rehabilitation period infected by the novel coronavirus;

step 2) carrying out panning on the fully human phage antibody library constructed in the step 1) by using biotinylated Spike1-RBD protein to obtain potential antibodies with RBD binding activity;

In order to further optimize the preparation method, the technical measures adopted by the invention also comprise the following steps:

further, the preparation method specifically comprises the following steps:

a. panning of the fully human antibody library Using biotinylated Spike1-RBD protein

Blocking phage antibodies at room temperature, adding antigens, incubating at room temperature, adding magnetic beads, incubating at room temperature, washing off unbound phage, eluting phage bound on magnetic beads, neutralizing eluate, infecting Escherichia coli in logarithmic growth phase with part of phage, and preparing phage for next round of panning; gradually increasing the screening strength of each round, and stopping the elutriation when the enrichment degree reaches more than 100 times;

b. screening of Single chain antibody Positive clones against Spike1-RBD Using phase Elisa

Selecting an escherichia coli monoclonal infected by the elutriated phage, inoculating a culture medium, transferring to a new culture medium after overnight culture, adding an auxiliary phage after the culture is carried out until the logarithmic growth phase, standing for infection, centrifuging, using the culture medium for overnight culture, centrifuging, and taking a phage supernatant for cloning identification; coating an enzyme standard plate with Spike1-RBD antigen, sealing overnight, adding phage supernatant for incubation, washing away unbound phage, adding antibody for incubation, washing, developing color, terminating reaction, reading at 450nm with an enzyme-labeling instrument, selecting clone with OD450>0.3 for sequencing, analyzing sequence, and removing molecules with potential development risk to obtain scFv single-chain antibody.

Further, the above preparation method further comprises a purification step of the scFv single chain antibody, which may be a purification method conventional in the art.

Compared with the prior art, the invention adopts the technical scheme, and has the following technical effects:

the invention establishes a fully human phage antibody library by using peripheral blood of a patient in a convalescent period infected by a novel coronavirus, elutriates RBD region protein of the virus Spike and cells over expressing the region, screens out an antibody with potential neutralizing activity by analyzing the binding activity of the antibody blocking ACE2 and the Spike protein on the cell and protein level, and prepares a complete IgG antibody and performs affinity maturation according to the antibody. The examples show that the fully humanized scFv single-chain antibody and the IgG antibody thereof obtained by the invention can recognize and combine the RBD region of the Spike protein, can effectively block the combination activity of ACE2 and the Spike protein, and the antibody with each concentration (30, 15, 7.5, 3.75, 1.875 and 0.938 mug/ml) is nontoxic to cells, safe and reliable, can obviously inhibit cytopathic effect caused by virus infection under a certain concentration, can effectively inhibit new coronavirus, and compared with the original sequence, the antibody sequence after affinity maturation has a certain degree of improved affinity, and obviously enhanced blocking effect on the Spike1-RBD and ACE2, and the antibodies have application value in treating and/or preventing the novel coronavirus SARS-CoV-2.

Drawings

FIG. 1 is a schematic diagram of ELISA detection of binding activity of panning terminated monoclonal scFv to Spike1-RBD protein in one embodiment of the present invention;

FIG. 2 is a schematic representation of the PAGE identification after scFv purification in one embodiment of the present invention;

FIG. 3 is a schematic diagram showing ELISA detection of binding activity of purified scFv to Spike1-RBD protein according to one embodiment of the present invention;

FIG. 4 is a schematic diagram of ELISA detection of purified scFv blocking the binding of Spike1-RBD to ACE2 in one embodiment of the present invention;

FIG. 5 is a diagram showing FACS detection of scFv blockade of the binding of Spike1-RBD to ACE2 in accordance with one embodiment of the present invention; wherein NC (negative control) is an unrelated sequence;

FIGS. 6A to 6G are schematic diagrams showing ELISA detection of the binding activity of an IgG form of antibody to Spike1-RBD protein according to an embodiment of the present invention; wherein NC (negative control) is an unrelated sequence;

FIGS. 7A-7F are schematic diagrams of ELISA detection of IgG antibodies blocking the binding of Spike1-RBD to ACE2 according to an embodiment of the present invention;

FIG. 8 is a graphical representation of the results of the scFv antibody neutralization activity assay in one embodiment of the present invention;

FIG. 9 is a diagram showing ELISA detection of binding activity of affinity matured sequences to Spike1-RBD in one embodiment of the present invention;

FIG. 10 is a schematic diagram of ELISA detection of IgG antibody blocking the binding of Spike1-RBD to ACE2 in one embodiment of the invention.

Detailed Description

The invention relates to an antibody, which can be combined with RBD region in the S1 subunit of Spike protein of novel coronavirus SARS-CoV-2 so as to block the combination activity of host cell membrane surface receptor ACE2 and Spike protein; the antibody is a neutralizing fully human antibody; wherein the antibody comprises a heavy chain VH and a light chain VL, each having the variable regions CDR1, CDR2 and CDR 3. The invention also relates to relative application of the antibody, in particular to preparation of a complete IgG antibody and an affinity mature antibody, and application of the corresponding antibody in treatment and/or prevention of novel coronavirus SARS-CoV-2.

The following description of the embodiments of the present invention will be made with reference to the accompanying drawings. The following examples are only for illustrating the technical solutions of the present invention more clearly, and the protection scope of the present invention is not limited thereby. Experimental procedures without specific conditions noted in the following examples were selected according to methods and conditions conventional in the art, or according to the commercial specifications.

Example 1-screening of neutralizing antibodies

This example is the screening of fully humanized scFv single chain antibodies, comprising the steps of:

(1) establishing a fully human phage antibody library;

peripheral blood from patients who had been infected with 2019-nCOV virus and recovered was collected and their serum titers were determined. Selecting high-titer sample, separating lymphocyte, extracting total RNA of cell, synthesizing cDNA, using specific antibody heavy chain primer and light chain primer to amplify variable region gene of antibody, cloning it on phage display carrier, and transferring it into host cell. And (3) evaluating the diversity and effectiveness of the antibody library by NGS sequencing and utilizing quality control indexes such as library capacity, clone positive rate, heavy and light chain pairing, CDR3 distribution, phage display rate and the like.

(2) Screening a phage library: panning the fully human antibody repertoire with biotinylated Spike1-RBD protein;

firstly, blocking phage antibody with blocking solution (PBST/5% skimmed milk powder) at room temperature for 2h, wherein the adding amount of phage is 10^10～12pfu, then 10. mu.g of antigen, incubated for 1h at room temperature, after which 50. mu.l of pre-blockedM-280Streptavidin magnetic beads, incubated at room temperature for 30 min. Washing off the unbound phage by PBST, eluting the phage bound on the magnetic beads by 0.1M HCl-Glycine, neutralizing the eluate by Tris-HCl, and taking part of phage to infect escherichia coli TG1 in logarithmic growth phase to prepare phage for the next round of panning. Gradually increasing the screening intensity of each round, and stopping the elutriation when the enrichment degree reaches more than 100 times.

(3) Screening single-chain antibody positive clones resisting Spike1-RBD by using phase Elisa;

a single clone of TGl infected with phage after four rounds of panning was selected and inoculated into a 96-well plate in a medium of 2 YT/2% glucose/(100. mu.g/ml Ampicilline). After overnight culture at 37 ℃/250rpm, the culture medium is transferred to a new culture medium, after the culture is carried out until logarithmic growth phase, M13K07 helper phage is added, and the culture medium is statically infected for 1h at 37 ℃. Centrifugation was carried out at 4000rpm for 15min, and 2 YT/(100. mu.g/ml Ampicilline)/(70. mu.g/ml Kanamycin) was used for overnight culture at 30 ℃. And centrifuging, taking the phage supernatant, and performing ELISA to identify clones. The Costar-9018 enzyme-labeled plate was coated with 0.5. mu.g/ml of Spike1-RBD antigen, blocked with 3% BSA overnight at 4 ℃ and incubated for 2h at 4 ℃ with phage supernatant. Unbound phage were washed away and Ml3 Bacteriophage antibody (HRP) was added and incubated for 1h at 4 ℃. After washing, adding TMB color development solution for color development, stopping reaction by using 2M HCl, reading at 450nm by using an enzyme-labeling instrument, judging that the clone with OD450> three times of baseline, namely OD450>0.3 is positive clone, and obtaining 470 positive clones in total. Clones with OD450>0.3 were selected for sequencing, Germline analysis and PTMs site analysis were performed on the sequences, 45 scFv single-chain antibodies were obtained in total after excluding molecules with potential development risk, and the results of ELISA detection of the binding activity of the panning terminating monoclonal scFv to Spike1-RBD protein are shown in FIG. 1.

The resulting antibody heavy chains of the 45 anti-Spike 1-RBD single chain antibodies are represented by VH, wherein the heavy chain variable regions are represented by CDR1, CDR2 and CDR 3; the light chain of the antibody is shown in VL, wherein the light chain variable region is shown in CDR1, CDR2 and CDR3, and the numbering and related sequence information of the corresponding anti-Spike 1-RBD single chain antibody is shown in Table 1 of the summary of the invention.

Example 2 expression purification of scFv

This example expresses and purifies 45 scFv single-chain antibodies selected in example 1, which comprises the following steps:

the Escherichia coli TGl after shaking is inoculated according to the ratio of 1:100 and cultured at 37 ℃ and 220 rpm. When OD is about 0.5, centrifuging at 8000rpm for 5min at room temperature to obtain bacterial liquid precipitate, inducing with IPTG, culturing at 30 deg.C for 12 hr, collecting expression supernatant, and purifying. The purification steps are as follows:

1) turning the bottle slightly upside down for several times to mix the medium evenly;

2) sucking a certain amount of medium, adding the medium into a column, wherein the height of the column is about 3-4 cm, and sealing the column when the medium is settled to the bottom;

3) draining the storage solution, and adding 10mL of equilibrium buffer solution to balance the chromatography medium;

4) centrifuging at 4000rpm at 4 deg.C for 10min in a centrifuge bottle, transferring the supernatant to a new centrifuge bottle, and centrifuging at 12000rpm at 4 deg.C for 30 min;

5) loading the sample, and controlling the flow rate to be 1 mL/min;

6)25mL of 10mM imidazole washing buffer is used for washing the column, and the flow rate is controlled to be 1 mL/min;

7)25mL of 20mM imidazole washing buffer is used for washing the column, and the flow rate is controlled to be 1 mL/min;

8) washing the column with 5mL of 250mM imidazole elution buffer solution, controlling the flow rate to be 1mL/min, and collecting elution solution;

9) concentrating, adding the eluate into an ultrafiltration tube, centrifuging at 1500rpm and 4 deg.C for 10min, and concentrating scFv;

10) PAGE identification and concentration determination.

The scFv of the 45 samples was purified, the detection result after purification is shown in fig. 2, each sample obtained more than 0.5mg, and the subsequent verification of the related activities is exemplified by HTS0422, HTS0433, HTS0446, and HTS 0483.

Example 3 detection of the binding Activity of scFv by ELISA

This example uses antibodies HTS0422, HTS0433, HTS0446 and HTS0483 as examples to detect binding of purified scFv to Spike1-RBD antigen using ELISA. The method comprises the following specific steps:

1)384-well plate coating antigen, each hole adding 25 u L1 u g/mL concentration of Spike1-RBD antigen, sealing, 4 degrees C coating overnight;

2) discarding the supernatant, washing 3 times with 100. mu.L Wash Buffer per well;

3) sealing each hole with 25 mu L of sealing liquid at room temperature for 1 hour, discarding the liquid of the sealed enzyme label plate, and washing each hole with 100 mu L of Wash Buffer for 3 times;

4) diluting scFv antibody with the highest concentration of 200 μ g/ml, four-fold gradient dilution, and 8 points in total;

5) diluted antibody 25 μ L/well was added to the appropriate wells and incubated for 2 hours at room temperature;

6) discarding the supernatant, drying the supernatant by using absorbent paper, and washing for 3 times by using 100 mu L of Wash Buffer;

7) adding diluted 25 mu L of Anti-C-myc-HRP into each well, and incubating for 1 hour at room temperature;

8) discarding the supernatant, drying the supernatant by using absorbent paper, and washing for 5 times by using 100 mu L of Wash Buffer;

9) adding 25 μ L of 1X TMB into each well, shaking in dark at room temperature, and developing for 10 min;

10) adding 25 mu L of stop solution into each hole;

11) reading a light absorption value of 450nm by using a microplate reader;

the detection results of the scFv antibody are shown in FIG. 3, and the antibodies HTS0422, HTS0433, HTS0446 and HTS0483 can be specifically combined with Spike1-RBD antigen and show a dose-effect relationship.

Example 4 ELISA detection of scFv blocking the binding of Spike1-RBD to ACE2 receptor

This example uses antibodies HTS0422, HTS0433, HTS0446 and HTS0483 as examples to detect purified scFv to block the binding of Spike1-RBD to ACE2 receptor using ELISA. The method comprises the following specific steps:

1)384-well plate coated antigen, each well is added with 25 μ L ACE2 antigen with the concentration of 1 μ g/mL, sealed and coated overnight at 4 ℃;

2) discarding the supernatant, washing 3 times with 100. mu.L Wash Buffer per well;

4) diluting the scFv antibody with the highest concentration of 200 mu g/ml, diluting by four times of gradient, mixing with Spike-RBD protein uniformly at 8 points, and incubating for 1 hour at room temperature;

5) add 25. mu.l of pre-treated scFv and Spike-RBD mix per well and incubate for 2 hours at room temperature;

6) discarding the supernatant, drying the supernatant by using absorbent paper, and washing for 3 times by using 100 mu L of Wash Buffer;

7) adding diluted 25 mu L of Anti-mFC-HRP into each well, and incubating for 1 hour at room temperature;

8) discarding the supernatant, drying the supernatant by using absorbent paper, and washing for 5 times by using 100 mu L of Wash Buffer;

9) adding 25 μ L of 1X TMB into each well, shaking in dark at room temperature, and developing for 10 min;

10) adding 25 mu L of stop solution into each hole;

11) the absorbance at 450nm was read using a microplate reader.

The detection results of the scFv antibody are shown in FIG. 4, and the antibodies HTS0422, HTS0433, HTS0446 and HTS0483 can block the combination of Spike1-RBD and AEC2 and show a dose-effect relationship.

Example 5-FACS detection of scFv to Block the binding of Spike1-RBD to ACE2 receptor

In this example, FACS was used to detect purified scFv to block the binding of Spike1-RBD to ACE2 receptor using antibodies HTS0422, HTS0433, HTS0446 and HTS0483 as examples. The method comprises the following specific steps:

1) diluting the antibody in a gradient manner with the highest concentration of 100 mu g/ml and four times of gradient dilution;

2) mixing 30 μ L of diluted antibody with 30 μ L of Spike1-RBD protein of 0.1 μ g/ml, and incubating on ice for 30 min;

3) digestion of cells, 96-well plate 3X 10 plates per well⁵A cell;

4) centrifuging at 4 deg.C and 1500rpm for 1min, and removing supernatant;

5) adding 50 μ L of the pretreated antigen-antibody mixture into each well, and incubating on ice for 30 min;

6) adding 150 μ L DPBS into each well, centrifuging at 4 deg.C and 1500rpm for 1min, and removing supernatant;

7) DPBS 1:800 dilution secondary antibody, 50 μ L heavy suspension, ice incubation for 30-60 min;

8) adding 150 μ L DPBS into each well, centrifuging at 4 deg.C and 1500rpm for 1min, and removing supernatant;

9) adding 200 μ L DPBS into each well, centrifuging at 4 deg.C and 1500rpm for 1min, and removing supernatant;

10) add 100. mu.L of DPBS resuspended cells per well and flow assay.

The detection results of the scFv antibody are shown in FIG. 5, and the antibodies HTS0422, HTS0433, HTS0446 and HTS0483 all block the combination of Spike1-RBD and AEC2, and show a dose-effect relationship.

Example 6 expression purification of intact IgG antibodies

This example is to prepare a complete IgG antibody from the VH and VL gene segments of the scFv single chain antibody of example 1, comprising the steps of: VH and VL gene fragments of scFv were subcloned into human IgG1 CH vector pTT5-hIgG1 and kappa light chain CL expression vector pTT5-hKappa, respectively, simultaneously transfected into 293F cells for expression and affinity purification by protein G.

Among all 45 positive clones, 37 whole IgG antibodies were selected to be expressed, HTS0390, HTS0414, HTS0422, HTS0433, HTS0446, HTS0448, HTS0460, HTS0461, HTS0471, HTS0472, HTS0476, HTS0477, HTS0478, HTS0483, HTS0777, HTS0778, HTS0829, HTS0842, HTS0888, HTS0889, HTS0895, HTS0896, HTS0910, HTS0916, HTS0917, HTS0921, HTS0922, HTS0936, HTS0943, HTS0944, HTS0948, HTS1021, HTS1049, HTS1072, HTS1099, HTS1125, HTS 1128.

Example 7 ELISA detection of the binding Activity of IgG antibodies

This example shows that the purified whole IgG antibody of example 6 was tested for binding to Spike1-RBD antigen by ELISA. The method comprises the following specific steps:

1)384-well plate coating antigen, each hole adding 25 u L1 u g/mL concentration of Spike1-RBD antigen, sealing, 4 degrees C coating overnight;

2) discarding the supernatant, washing 3 times with 100. mu.L Wash Buffer per well;

4) diluting IgG antibody with the highest concentration of 50 mug/ml, and performing three-time gradient dilution for 12 points;

5) diluted antibody 25 μ L/well was added to the appropriate wells and incubated for 2 hours at room temperature;

6) discarding the supernatant, drying the supernatant by using absorbent paper, and washing for 3 times by using 100 mu L of Wash Buffer;

7) adding diluted 25 mu L of Anti-human-FC-HRP into each hole, and incubating for 1 hour at room temperature;

8) discarding the supernatant, drying the supernatant by using absorbent paper, and washing for 5 times by using 100 mu L of Wash Buffer;

9) adding 25 μ L of 1X TMB into each well, shaking in dark at room temperature, and developing for 10 min;

10) adding 25 mu L of stop solution into each hole;

11) reading a light absorption value of 450nm by using a microplate reader;

the results of the above IgG antibody tests are shown in FIGS. 6A-6G, and the IgG antibodies were able to specifically bind to Spike1-RBD antigen and showed dose-response relationship.

Example 8 ELISA detection of IgG antibodies blocking the binding of Spike1-RBD to ACE2 receptor

This example uses ELISA to detect that the purified whole IgG antibody of example 6 blocks the binding of Spike1-RBD to ACE2 receptor. The method comprises the following specific steps:

1)384-well plate coated antigen, each well is added with 25 μ L ACE2 antigen with the concentration of 1.5 μ g/mL, sealed and coated overnight at 4 ℃;

2) discarding the supernatant, washing 3 times with 100. mu.L Wash Buffer per well;

4) diluting IgG antibody with the highest concentration of 100 mu g/ml, diluting with three times of gradient, mixing with Spike-RBD protein at 11 points, and incubating for 1 hour at room temperature;

5) add 25. mu.l of the pre-treated IgG antibody and the Spike-RBD mixture per well and incubate for 2 hours at room temperature;

6) discarding the supernatant, drying the supernatant by using absorbent paper, and washing for 3 times by using 100 mu L of Wash Buffer;

7) adding diluted 25 mu L of Anti-mFC-HRP into each well, and incubating for 1 hour at room temperature;

8) discarding the supernatant, drying the supernatant by using absorbent paper, and washing for 5 times by using 100 mu L of Wash Buffer;

9) adding 25 μ L of 1X TMB into each well, shaking in dark at room temperature, and developing for 10 min;

10) adding 25 mu L of stop solution into each hole;

11) the absorbance at 450nm was read using a microplate reader.

The detection results of the IgG antibodies are shown in FIGS. 7A-7F, and the IgG antibodies can block the combination of Spike1-RBD and AEC2 and show a dose-effect relationship, wherein the HTS0422, HTS0433, HTS0483, HTS0446 and HTS0778 have the best effect.

Example 9 antibody toxicity test

In this example, the CCK8 experiment is performed to verify the antibody toxicity effects of antibodies HTS0422, HTS0433, HTS0483, HTS0446 and HTS0390, and the specific steps are as follows:

(1) serum-free medium was used to dilute the anti-neocoronaviruse antibodies HTS0422, HTS0433l, HTS0446, HTS0390, HTS0483 at an initial antibody concentration of 60 μ g/ml, 2-fold gradient dilution, with 6 dilutions co-diluted, i.e. antibody concentrations formulated at 60, 30, 15, 7.5, 3.75, 1.875 μ g/ml.

(2) In 96-well cell culture plates, 100. mu.l of antibody fluid was added at each concentration (60, 30, 15, 7.5, 3.75, 1.875. mu.g/ml) per well. Vero-E6 cells (1X 10) were then added⁵Cell concentration/ml was suspended in 10% FBS in MEM medium) 100 μ l, antibody final concentrations were: 30. 15, 7.5, 3.75, 1.875, 0.938 mug/ml. The cell culture plate is vibrated, mixed evenly and then placed in 5 percent CO₂In the incubator, 4 multiple wells were set.

(3) After 6 days of incubation, 20. mu.l/well of CCK-8 reagent (MCE, USA) was added to each well, and after 3 hours of incubation, OD at 450nm was measured using a microplate reader to analyze the dose-toxic effect of the antibody on the cells, and the results are shown in the following table:

the results of the above CCK-8 assay show that the antibody tested at each concentration (30, 15, 7.5, 3.75, 1.875, 0.938. mu.g/ml) had no toxic effect on Vero-E6 cells compared to the untreated cell control.

Example 10 detection of neutralizing Activity of antibodies

In this example, the neutralizing activity of HTS0422, HTS0433, HTS0446, HTS0483, and HTS0390 antibodies was tested by a euvirus blocking assay, which specifically comprises the following steps:

(1) serum-free medium was used to dilute the anti-neocoronavirus antibodies HTS0422, HTS0433, HTS0446, HTS0483 and HTS0390 at an initial antibody concentration of 60 μ g/ml, 2-fold gradient dilutions, with 12 dilutions co-diluted, i.e. formulated antibody concentrations of 60, 30, 15, 7.5, 3.75, 1.875, 0.938, 0.469, 0.235, 0.118, 0.059, 0.029 μ g/ml.

(2) In a 96-well plate, 50. mu.l of antibody solution was added at each concentration, followed by an equal volume of 50. mu.l of neocoronaviruse containing 100TCID50 at final antibody concentrations of 30, 15, 7.5, 3.75, 1.875, 0.938, 0.469, 0.235, 0.118, 0.059, 0.029, 0.0145. mu.g/ml, mixed and incubated in a 35 ℃ incubator for 60 min. Freshly prepared Vero-E6 cell suspension (2X 10) was added to each well⁵Ml in 10% FBS-MEM) was mixed with 100. mu.l and incubated in a cell culture chamber containing 5% CO2 at 35 ℃ for 6 days. Each antibody concentration tested was plated in 4 replicates.

(3) Cell growth was observed microscopically from day 2 after inoculation, and cytopathic effect (CPE) was observed and recorded at day 4. And finally judging the result on the 6 th day according to the cytopathic effect. The neutralization efficiency of the antibody, i.e., the lowest concentration of antibody that can protect 50% of the cells from infection with 100TCID50 virus fluid, was calculated.

(4) The effect of the antibody-treated virus on the pathology of Vero E6 cells was observed under a microscope at various concentrations, and the inhibitory effect of the antibody on the novel coronavirus was analyzed, and the results are shown in the following table and fig. 8.

According to the results, the cytopathic effect caused by virus infection can be obviously inhibited by the HTS0422 which is more than or equal to 1.875ug/ml, the HTS0433 which is more than or equal to 1.875ug/ml, the HTS0446 which is more than or equal to 7.5ug/ml and the HTS0483 which is more than or equal to 1.875 ug/ml. HTS0390, however, had no significant antiviral effect at all concentrations tested.

Example 11 affinity maturation of antibodies

The above examples prove that the binding effect and blocking effect of HTS0422, HTS0433, HTS0446 and HTS0483 are the best, and the affinity maturation of HTS0433 and HTS0483 is selected, and the specific steps are as follows:

(1) design point mutation primer, design NNS (N stands for arbitrary base, S stands for base C or G) aiming at CDR region of HTS0433 and HTS0483

(2) Plasmids were circularized using either HTS0433 or HTS0483 as templates.

	Volume (uL)
		Fn-primer(2μM)	5
Rn-primer(2μM)	5
		Template plasmid (100ng/uL)	1
PrimerSRAR Max Premix	5
		Water (W)	34
Total volume	50

Remarking: fn and Rn are based on sequences of HTS0433 or HTS0483 light chain and heavy chain CDR1, CDR2 and CDR3 regions, only a single site in the CDR region is mutated each time, the base of the site is represented by NNS, forward primers are named as F1-primer, F2-primer … … Fn-primer, and reverse primers are named as R1-primer and R2-primer … … Rn-primer.

The reaction solution was added to the PCR tube as above and mixed well. Placing the PCR reaction tube in a PCR instrument, and setting reaction conditions as follows: denaturation at 95 deg.C for 5 min; 30S at 95 ℃, 30S at 58 ℃ and 4min at 72 ℃; 10min at 72 ℃; the product can be stored for a short time at 4 ℃ and used for subsequent experiments.

(3) And (3) recovering the plasmid by using the PCR product recovery kit, and carrying out the transformation of the PCR product and the preparation of the plasmid according to a conventional method.

(4) Clones with each site-directed mutation were induced to express scFv and tested for scFv blocking activity, the specific procedures are shown in example 2 and example 5.

(5) The high affinity mutations were identified by monoclonality, step 4. High affinity clones were sequenced. The sequences after affinity maturation are shown in table 2 of the summary section.

Example 12 ELISA detection of the binding Activity of antibodies after affinity maturation

In this example, the binding force between the affinity matured antibody prepared in example 11 and the Spike1-RBD antigen was measured by ELISA, which was performed in the same manner as in example 7, and the results are shown in FIG. 9. The experimental results show that the affinity of the antibody sequence after the affinity maturation is improved compared with the original sequence.

Example 13 ELISA detection of antibody blockade of the binding of Spike1-RBD to ACE2 receptor after affinity maturation

In this example, ELISA was used to detect the binding activity of the affinity matured antibody prepared in example 11 for blocking the binding activity of Spike1-RBD and ACE2, which was performed in the same manner as in example 8, and the results are shown in FIG. 10. The experimental results show that the blocking effect of AGE0003 and AGE0004 is obviously enhanced compared with the original sequence of the antibody sequence after affinity maturation.

The above examples show that the fully humanized scFv single chain antibody and IgG antibody thereof obtained by screening can recognize and bind to RBD region of Spike protein, can effectively block the binding activity of ACE2 and Spike protein, have no toxicity to cells, can obviously inhibit cytopathic effect caused by virus infection, and obviously enhance the affinity of antibody sequence after the affinity maturation and the blocking effect of Spike1-RBD and ACE2, and have application value in treating and/or preventing novel coronavirus SARS-CoV-2.

The embodiments of the present invention have been described in detail, but the embodiments are merely examples, and the present invention is not limited to the embodiments described above. Any equivalent modifications and substitutions to those skilled in the art are also within the scope of the present invention. Accordingly, equivalent changes and modifications made without departing from the spirit and scope of the present invention should be covered by the present invention.

Sequence listing

<110> Shanghai Xiang Yao Biotechnology Limited liability company

Zhejiang Xiangyao biomedical Co.,Ltd.

<120> a novel coronavirus SARS-CoV-2 neutralizing antibody and application thereof

<150> 202010188367.6

<151> 2020-03-17

<160> 408

<170> SIPOSequenceListing 1.0

<210> 1

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 1

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 2

<211> 132

<212> PRT

<213> VH(Artificial Sequence)

<400> 2

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Met Val

115 120 125

Thr Val Ser Ser

130

<210> 3

<211> 132

<212> PRT

<213> VH(Artificial Sequence)

<400> 3

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val

115 120 125

Thr Val Ser Ser

130

<210> 4

<211> 132

<212> PRT

<213> VH(Artificial Sequence)

<400> 4

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val

115 120 125

Thr Val Ser Ser

130

<210> 5

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 5

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Asp Ile Ala Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 6

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 6

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 7

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 7

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 8

<211> 122

<212> PRT

<213> VH(Artificial Sequence)

<400> 8

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Phe Ala Gln Lys Phe

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Asp Arg Gly Phe Ser Ile Val Ser Tyr Ala Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 9

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 9

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 10

<211> 128

<212> PRT

<213> VH(Artificial Sequence)

<400> 10

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Ser Ala Tyr His Gly Asn Thr Asn Tyr Ala Gln Lys Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

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

85 90 95

Ala Arg Gly Leu Ala Pro Ser Tyr Cys Gly Gly Asp Cys Tyr Pro Arg

100 105 110

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

115 120 125

<210> 11

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 11

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 12

<211> 128

<212> PRT

<213> VH(Artificial Sequence)

<400> 12

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

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

85 90 95

Ala Arg Gly Leu Ala Pro Ser Tyr Cys Gly Gly Asp Cys Tyr Pro Arg

100 105 110

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

115 120 125

<210> 13

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 13

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 14

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 14

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Gln Glu Arg Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Thr Val Thr Val Ser Ser

115

<210> 15

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 15

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Gln Glu Arg Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 16

<211> 123

<212> PRT

<213> VH(Artificial Sequence)

<400> 16

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

1 5 10 15

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

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Ser Arg Ser Pro Ser Ile Ala Ala Ala Ala Asn Ala Phe Asp Ile

100 105 110

Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 17

<211> 122

<212> PRT

<213> VH(Artificial Sequence)

<400> 17

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Phe Ala Gln Lys Phe

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Asp Arg Gly Phe Ser Ile Val Ser Tyr Ala Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 18

<211> 116

<212> PRT

<213> VH(Artificial Sequence)

<400> 18

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Arg Gly Asp Ala Phe Asp Ile Trp Gly Gln Gly Thr Thr Val

100 105 110

Thr Val Ser Ser

115

<210> 19

<211> 122

<212> PRT

<213> VH(Artificial Sequence)

<400> 19

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

1 5 10 15

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

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 20

<211> 121

<212> PRT

<213> VH(Artificial Sequence)

<400> 20

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser Ile Thr Gln Ile

20 25 30

Ile Tyr Tyr Trp Ala Trp Ile Arg Gln Pro Pro Gly Arg Gly Leu Glu

35 40 45

Trp Ile Gly Ser Ile Tyr Tyr Arg Gly Ser Thr Ser Ser Asn Pro Ser

50 55 60

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

65 70 75 80

Ser Leu Asn Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg Ala Val Arg His Asp Tyr Asn Tyr Phe Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 21

<211> 122

<212> PRT

<213> VH(Artificial Sequence)

<400> 21

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

1 5 10 15

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

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 22

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 22

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 23

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 23

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 24

<211> 122

<212> PRT

<213> VH(Artificial Sequence)

<400> 24

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

1 5 10 15

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

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 25

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 25

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Leu Glu Val Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Met Val Thr Val Ser Ser

115

<210> 26

<211> 130

<212> PRT

<213> VH(Artificial Sequence)

<400> 26

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Glu Phe Thr Phe Ser Asn Ala

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

115 120 125

Ser Ser

130

<210> 27

<211> 116

<212> PRT

<213> VH(Artificial Sequence)

<400> 27

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Thr Val Ser Ser

115

<210> 28

<211> 130

<212> PRT

<213> VH(Artificial Sequence)

<400> 28

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

115 120 125

Ser Ser

130

<210> 29

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 29

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Ala Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser

115

<210> 30

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 30

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Leu Glu Val Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 31

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 31

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ala Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 32

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 32

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 33

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 33

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 34

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 34

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 35

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 35

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 36

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 36

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105

<210> 37

<211> 103

<212> PRT

<213> VL(Artificial Sequence)

<400> 37

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Glu Ala Phe Gly Gly

85 90 95

Gly Thr Lys Val Glu Ile Lys

100

<210> 38

<211> 106

<212> PRT

<213> VL(Artificial Sequence)

<400> 38

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Ile Tyr Tyr Cys Gln Gln His Asn Ser Tyr Pro Thr

85 90 95

Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 39

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 39

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 40

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 40

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 41

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 41

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 42

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 42

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Leu Leu

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 43

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 43

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 44

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 44

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

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Gly Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 45

<211> 106

<212> PRT

<213> VL(Artificial Sequence)

<400> 45

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Gly Asn Tyr Trp Thr

85 90 95

Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 46

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 46

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 47

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 47

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 48

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 48

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser Trp

85 90 95

Ala Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 49

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 49

Ala Ile Arg Met Thr Gln Phe Pro Ser Thr Leu Ser Ala Ser Val Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser His

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 50

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 50

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Tyr Asp Asn Leu Pro Leu

85 90 95

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

100 105

<210> 51

<211> 112

<212> PRT

<213> VL(Artificial Sequence)

<400> 51

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

1 5 10 15

Glu Ser Ala Ser Leu Ser Cys Arg Ser Ser Gln Ser Leu Leu His Arg

20 25 30

Ser Gly His Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

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

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly

85 90 95

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

100 105 110

<210> 52

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 52

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 53

<211> 112

<212> PRT

<213> VL(Artificial Sequence)

<400> 53

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

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

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

35 40 45

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

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

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

100 105 110

<210> 54

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 54

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

His Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Arg

100 105

<210> 55

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 55

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

100 105

<210> 56

<211> 112

<212> PRT

<213> VL(Artificial Sequence)

<400> 56

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

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

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

35 40 45

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

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Gly Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

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

100 105 110

<210> 57

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 57

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 58

<211> 113

<212> PRT

<213> VL(Artificial Sequence)

<400> 58

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

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser

20 25 30

Asp Gly Asn Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly Gln Ser

35 40 45

Pro Arg Arg Leu Ile Tyr Lys Val Ser Asn Arg Asp Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly

85 90 95

Thr His Trp Pro Pro Asn Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

100 105 110

Lys

<210> 59

<211> 109

<212> PRT

<213> VL(Artificial Sequence)

<400> 59

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Met Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 60

<211> 112

<212> PRT

<213> VL(Artificial Sequence)

<400> 60

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

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser

20 25 30

Asp Gly Asn Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly Gln Ser

35 40 45

Pro Arg Arg Leu Ile Tyr Lys Val Ser Asn Arg Asp Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly

85 90 95

Thr His Trp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105 110

<210> 61

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 61

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 62

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 62

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Glu Gln Leu Lys Ser Tyr Pro Pro

85 90 95

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

100 105

<210> 63

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 63

Gly Val Thr Val Ser Ser Asn Tyr

1 5

<210> 64

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 64

Gly Phe Thr Phe Asp Asp Tyr Ala

1 5

<210> 65

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 65

Gly Phe Thr Val Ser Ser Asn Tyr

1 5

<210> 66

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 66

Gly Tyr Thr Phe Thr Gly Tyr Tyr

1 5

<210> 67

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 67

Gly Tyr Thr Phe Thr Ser Tyr Gly

1 5

<210> 68

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 68

Gly Phe Thr Val Gly Ser Asn Tyr

1 5

<210> 69

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 69

Gly Ile Thr Val Ser Ser Asn Tyr

1 5

<210> 70

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 70

Gly Phe Thr Phe Ser Ser Tyr Ala

1 5

<210> 71

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 71

Asp Phe Thr Val Ser Ser Asn Tyr

1 5

<210> 72

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 72

Gly Phe Thr Phe Ser Thr Tyr Ala

1 5

<210> 73

<211> 10

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 73

Gly Gly Ser Ile Thr Gln Ile Ile Tyr Tyr

1 5 10

<210> 74

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 74

Gly Phe Thr Val Ser Arg Asn Tyr

1 5

<210> 75

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 75

Glu Phe Thr Phe Ser Asn Ala Trp

1 5

<210> 76

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 76

Gly Phe Thr Phe Ser Asn Ala Trp

1 5

<210> 77

<211> 7

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 77

Ile Tyr Ser Gly Gly Ser Thr

1 5

<210> 78

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 78

Ile Ser Trp Asn Ser Gly Ser Ile

1 5

<210> 79

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 79

Ile Asn Pro Asn Ser Gly Ala Thr

1 5

<210> 80

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 80

Ile Ser Ala Tyr His Gly Asn Thr

1 5

<210> 81

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 81

Ile Ser Gly Phe His Gly Asn Thr

1 5

<210> 82

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 82

Ile Ser Tyr Asp Gly Ser Asn Lys

1 5

<210> 83

<211> 7

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 83

Ile Tyr Pro Gly Gly Ser Thr

1 5

<210> 84

<211> 7

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 84

Ile Tyr Tyr Arg Gly Ser Thr

1 5

<210> 85

<211> 7

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 85

Ile Tyr Ser Gly Gly Thr Thr

1 5

<210> 86

<211> 10

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 86

Ile Lys Ser Lys Thr Asp Gly Gly Thr Thr

1 5 10

<210> 87

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 87

Ala Arg Asp Leu Val Ser Ser Gly Met Asp Val

1 5 10

<210> 88

<211> 25

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 88

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

1 5 10 15

Pro Lys Ala His Trp Tyr Phe Asp Leu

20 25

<210> 89

<211> 12

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 89

Ala Arg Asp Leu Asp Ile Ala Gly Gly Met Asp Val

1 5 10

<210> 90

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 90

Ala Arg Asp Leu Val Val Tyr Gly Met Asp Val

1 5 10

<210> 91

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 91

Ala Arg Asp Leu Val Val Phe Gly Met Asp Val

1 5 10

<210> 92

<211> 15

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 92

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

1 5 10 15

<210> 93

<211> 21

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 93

Ala Arg Gly Leu Ala Pro Ser Tyr Cys Gly Gly Asp Cys Tyr Pro Arg

1 5 10 15

Ala Pro Phe Asp Tyr

<210> 94

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 94

Ala Arg Asp Leu Val Tyr Tyr Gly Met Asp Val

1 5 10

<210> 95

<211> 12

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 95

Ala Arg Asp Leu Gln Glu Arg Gly Gly Met Asp Val

1 5 10

<210> 96

<211> 16

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 96

Ala Ser Arg Ser Pro Ser Ile Ala Ala Ala Ala Asn Ala Phe Asp Ile

1 5 10 15

<210> 97

<211> 10

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 97

Ala Arg Asp Arg Gly Asp Ala Phe Asp Ile

1 5 10

<210> 98

<211> 15

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 98

Ala Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val

1 5 10 15

<210> 99

<211> 13

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 99

Ala Arg Ala Val Arg His Asp Tyr Asn Tyr Phe Asp Tyr

1 5 10

<210> 100

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 100

Ala Arg Asp Leu Gly Pro Tyr Gly Met Asp Val

1 5 10

<210> 101

<211> 12

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 101

Ala Arg Asp Leu Leu Glu Val Gly Gly Met Asp Val

1 5 10

<210> 102

<211> 21

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 102

Thr Thr Asp Gln Pro Glu Gly Tyr Tyr Gly Ser Gly Ser Val Tyr Tyr

1 5 10 15

Tyr Gly Met Asp Val

<210> 103

<211> 10

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 103

Ala Arg Thr Leu Tyr Asp Ala Phe Asp Ile

1 5 10

<210> 104

<211> 11

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 104

Ala Arg Asp Leu Val Ala Tyr Gly Met Asp Val

1 5 10

<210> 105

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 105

Gln Gly Ile Ser Ser Trp

1 5

<210> 106

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 106

Gln Ser Ile Ser Ser Tyr

1 5

<210> 107

<211> 7

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 107

Gln Ser Val Ser Ser Ser Tyr

1 5

<210> 108

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 108

Gln Ser Ile Asn Ser Trp

1 5

<210> 109

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 109

Gln Gly Ile Ser Ser Tyr

1 5

<210> 110

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 110

Gln Ala Ile Ser Asn Trp

1 5

<210> 111

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 111

Gln Thr Ile Thr Asp Trp

1 5

<210> 112

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 112

Gln Ser Ile Gly Ser Trp

1 5

<210> 113

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 113

Gln Asp Ile Ser Asn Tyr

1 5

<210> 114

<211> 11

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 114

Gln Ser Leu Leu His Arg Ser Gly His Asn Tyr

1 5 10

<210> 115

<211> 11

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 115

Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr

1 5 10

<210> 116

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 116

Gln Ile Ile Ser Asp Trp

1 5

<210> 117

<211> 7

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 117

Glu Ser Val Ser Ser Ser Tyr

1 5

<210> 118

<211> 11

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 118

Gln Ser Leu Val His Ser Asp Gly Asn Thr Tyr

1 5 10

<210> 119

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 119

Gln Ser Ile Ser Ser Trp

1 5

<210> 120

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 120

Ala Ala Ser

<210> 121

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 121

Gly Ala Ser

<210> 122

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 122

Lys Ala Ser

<210> 123

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 123

Asp Ala Ser

<210> 124

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 124

Glu Ala Ser

<210> 125

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 125

Leu Gly Ser

<210> 126

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 126

Lys Val Ser

<210> 127

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 127

Gln Gln Ala Asn Ser Phe Pro Pro Ala

1 5

<210> 128

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 128

Gln Gln Ser His Ser Thr Pro Tyr Thr

1 5

<210> 129

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 129

Gln Gln Ser Tyr Ser Thr Pro Arg Thr

1 5

<210> 130

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 130

Gln Gln Ser Tyr Ser Thr Pro Tyr Thr

1 5

<210> 131

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 131

Gln Gln Tyr Gly Ser Ser Ser Tyr Thr

1 5

<210> 132

<211> 5

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 132

Gln Gln Ala Glu Ala

1 5

<210> 133

<211> 8

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 133

Gln Gln His Asn Ser Tyr Pro Thr

1 5

<210> 134

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 134

Gln Gln Leu Asn Ser Tyr Pro Phe Thr

1 5

<210> 135

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 135

Gln Gln Leu Asn Ser Tyr Pro Pro Tyr Thr

1 5 10

<210> 136

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 136

Gln Gln Ser Tyr Ser Thr Leu Leu Thr

1 5

<210> 137

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 137

Gln Gln Tyr Gly Ser Ser Pro Leu Thr

1 5

<210> 138

<211> 8

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 138

Gln Gln Tyr Gly Asn Tyr Trp Thr

1 5

<210> 139

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 139

Gln Gln Ser Tyr Ser Thr Pro Leu Thr

1 5

<210> 140

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 140

Gln Gln Tyr Asn Ser Tyr Ser Trp Ala

1 5

<210> 141

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 141

Gln Gln Tyr Asn Ser Tyr Ser His Thr

1 5

<210> 142

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 142

Gln Gln Tyr Asp Asn Leu Pro Leu Phe Thr

1 5 10

<210> 143

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 143

Met Gln Gly Leu Gln Pro Pro Tyr Thr

1 5

<210> 144

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 144

Met Gln Ala Leu Gln Thr Pro Tyr Thr

1 5

<210> 145

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 145

Gln Gln Tyr Asn Ser Asp Ser Gly His Thr

1 5 10

<210> 146

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 146

Gln Gln Ala Asn Ser Phe Pro Pro Thr

1 5

<210> 147

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 147

Met Gln Ala Leu Gln Thr Pro Phe Thr

1 5

<210> 148

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 148

Gln Gln Tyr Gly Ser Ser Pro Tyr Thr

1 5

<210> 149

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 149

Met Gln Gly Thr His Trp Pro Pro Asn Thr

1 5 10

<210> 150

<211> 11

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 150

Gln Gln Tyr Asn Ser Tyr Ser Asp Met Tyr Thr

1 5 10

<210> 151

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 151

Met Gln Gly Thr His Trp Pro Tyr Thr

1 5

<210> 152

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 152

Glu Gln Leu Lys Ser Tyr Pro Pro Tyr Thr

1 5 10

<210> 153

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 153

caggttcagc tggtgcagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 154

<211> 396

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 154

gaggtgcagc tggtggagtc cgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcacaat ggtcaccgtc tcgagt 396

<210> 155

<211> 396

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 155

gaggtgcagc tggtggagtc cgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatt tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatgg acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcactgtc tcgagt 396

<210> 156

<211> 396

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 156

caggttcagc tggtgcagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcaccgtc tcgagt 396

<210> 157

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 157

gaggtgcaac tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agatctggat 300

atagccgggg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagt 354

<210> 158

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 158

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agacctagta 300

gtctacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 159

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 159

gaggtgcagc tggtggagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtattcggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 160

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 160

gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagt 366

<210> 161

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 161

gaggtgcagc tggtggagac tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 162

<211> 384

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 162

gaggtgcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcagcgctt accatggtaa cacaaactat 180

gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240

atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagaggcctg 300

gccccatcat attgtggtgg tgactgctat cctcgggccc catttgacta ctggggccag 360

ggaaccctgg tcaccgtctc gagt 384

<210> 163

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 163

gaggtgcagc tggtgcagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accctggtca ccgtctcgag t 351

<210> 164

<211> 384

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 164

gaggtgcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcagcggtt tccacggtaa cacaaactat 180

gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240

atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagaggcctg 300

gccccatcat attgtggtgg tgactgctat cctcgggccc catttgacta ctggggccag 360

ggaaccctgg tcaccgtctc gagt 384

<210> 165

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 165

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcggt agcaactaca tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcactt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agacttagtc 300

tactacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 166

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 166

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggaat caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggcagatt cagcatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatcttcag 300

gagcgaggcg gtatggacgt ctggggccaa gggaccacgg tcaccgtctc gagt 354

<210> 167

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 167

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggaat caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggcagatt cagcatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatcttcag 300

gagcgaggcg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagt 354

<210> 168

<211> 369

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 168

gaggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagccgatcc 300

cccagtatag cagcagccgc taatgctttt gatatctggg gccaagggac cacggtcacc 360

gtctcgagt 369

<210> 169

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 169

caggtgcagc tggtggagtc tggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagt 366

<210> 170

<211> 348

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 170

caggtccagc tggtgcagtc tgggggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtacag cctctgactt caccgtcagt agcaactaca tgacctgggt ccgccaggct 120

ccagggaagg gactggagtg ggtctcactt atttatcccg gtggtagcac atactacgca 180

gactccctga agggccgatt caccatctcc agagacaatt ccaagaacac gctatacctt 240

caaatgaaca gcctgagagt tgaggacacg gctgtgtatt actgtgcgag agaccggggc 300

gatgcatttg atatctgggg ccaagggacc acggtcaccg tctcgagt 348

<210> 171

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 171

gaggtgcagc tggtggagtc cgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccgagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aaggcaccct ggtcaccgtc 360

tcgagt 366

<210> 172

<211> 363

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 172

caggtgcagc tacaacagtg gggcccagga ctggtgaagc cttcggagac cctgtccctc 60

acctgtagcg tctctggtgg ctccatcacg cagattattt actactgggc ctggatccgc 120

cagcccccag ggagggggct ggagtggatt gggagtatct actatagggg gagcacctcc 180

tccaacccgt ccctcaagag tcgagtcacc atatccgtag acacgtccaa gaaccagttc 240

tccctgaacc taacctctgt gaccgccgca gacacggctg tgtattactg tgcgagggcg 300

gttagacatg actacaacta ttttgactac tggggccagg gaaccctggt caccgtctcg 360

agt 363

<210> 173

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 173

gaggtgcagc tgttggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aagggaccct ggtcaccgtc 360

tcgagt 366

<210> 174

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 174

gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggagt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gcggtaccac atactacgca 180

gactccgtga agggcagatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatctgggg 300

ccatacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 175

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 175

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 176

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 176

gaagtgcagc tggtggagtc tgggggaggc gtggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aagggaccct ggtcaccgtc 360

tcgagt 366

<210> 177

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 177

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctctta 300

gaagtagggg gtatggacgt ctggggccaa gggacaatgg tcaccgtctc gagt 354

<210> 178

<211> 390

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 178

gaggtgcaac tggtggagtc tgggggaggc ttggtaaagc ctggggggtc ccttagactc 60

tcctgtgcag cctctgagtt cactttcagt aacgcctgga tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggttggccgt attaaaagca aaactgatgg tgggacaaca 180

gactacgctg cacccgtgaa aggcagattc accatctcaa gagatgattc aaaaaacacg 240

ctgtatctgc aaatgaacag cctgaaaacc gaggacacag ccgtgtatta ctgtaccaca 300

gatcaaccgg agggatacta tggttcgggg agtgtctact actacggtat ggacgtctgg 360

ggccaaggga ccacggtcac cgtctcgagt 390

<210> 179

<211> 348

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 179

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcttgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaatac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag gactttatat 300

gatgcttttg atatctgggg ccaagggacc acggtcaccg tctcgagt 348

<210> 180

<211> 390

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 180

gaggtgcaac tggtggagtc tgggggaggc ttggtaaagc ctggggggtc ccttagactc 60

tcctgtgcag cctctggatt cactttcagt aacgcctgga tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggttggccgt attaaaagca aaactgatgg tgggacaaca 180

gactacgctg cacccgtgaa aggcagattc accatctcaa gagatgattc aaaaaacacg 240

ctgtatctgc aaatgaacag cctgaaaacc gaggacacag ccgtgtatta ctgtaccaca 300

gatcaaccgg agggatacta tggttcgggg agtgtctact actacggtat ggacgtctgg 360

ggccaaggga ccacggtcac cgtctcgagt 390

<210> 181

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 181

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agatctcgtt 300

gcctacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 182

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 182

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctctta 300

gaagtagggg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagt 354

<210> 183

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 183

gacatcgtga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60

atcacttgtc gggcgagtca gggtattagc agctggttag cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttacta ttgtcaacag gctaacagtt tccctccggc tttcggccct 300

gggaccaaag tggatatcaa a 321

<210> 184

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 184

gccatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagttcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agtcacagta ccccgtacac ttttggccaa 300

gggaccaagg tggaaatcaa a 321

<210> 185

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 185

gacatcgtga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cccctcggac gttcggccag 300

gggaccaagc tggagatcaa a 321

<210> 186

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 186

gccatccgga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cccctcggac ttttggccaa 300

gggaccaagg tggaaatcaa a 321

<210> 187

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 187

gccatccgga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta ccccgtacac ttttggccag 300

gggaccaagc tggagatcaa a 321

<210> 188

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 188

gaaattgtgt tgacacagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcctcgta cacttttggc 300

caggggacca agctggagat caaa 324

<210> 189

<211> 309

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 189

gccatccgga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60

atcacttgtc gggcgagtca gggtattagc agctggttag cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttacta ttgtcaacag gctgaggctt tcggcggagg gaccaaggtg 300

gagatcaaa 309

<210> 190

<211> 318

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 190

gccatccagt tgacccagtc tccttccacc ctgtctgcat ctgtcggaga cagagtcacc 60

atcacttgcc gggccagtca gagtattaat tcctggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaaactcct gatctataag gcgtctcatt tacaaagtgg cgtcccttca 180

aggttcagcg gcagtggatc tgggacagat ttcactctta ccatcagtag cctgcagcct 240

gatgattttg caatttatta ctgccaacag cataattctt atccgacctt cggccaaggg 300

accaaggtgg aaatcaaa 318

<210> 191

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 191

gaaattgtgt tgacgcagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaagaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaggtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accctttcac tttcggcgga 300

gggaccaagg tggagatcaa a 321

<210> 192

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 192

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta ccccgtacac ttttggccag 300

gggaccaagc tggagatcaa a 321

<210> 193

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 193

gccatccagt tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tggggcagaa ttcactctca caatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accctccgta cacttttggc 300

caagggacca aggtggaaat caaa 324

<210> 194

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 194

gccatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cactcctcac tttcggcgga 300

gggaccaagg tggagatcaa a 321

<210> 195

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 195

gacatcgtga tgacccagtc tccatccttc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca caatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accctccgta cacttttggc 300

caagggacca aggtggaaat caaa 324

<210> 196

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 196

gaaattgtgt tgacgcagtc tccagccacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgcg gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggcctgg cgcccaggct cctcatctat gatgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccgct cactttcggc 300

ggagggacca aggtggagat caaa 324

<210> 197

<211> 318

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 197

gacatccagt tgacccagtc tccctccacc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca ggctattagt aactggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgag gcgtctaatt tagaaagtgg ggtcccatcg 180

aggttcagcg gcagtggttc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgattttg caacttatta ctgccaacag tatggtaatt attggacgtt cggccaaggg 300

accaaggtgg aaatcaaa 318

<210> 198

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 198

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cccctctgac gttcggccag 300

gggaccaagc tggagatcaa a 321

<210> 199

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 199

gacatcgtga tgacccagtc ttcatcctcc ctgtctgcat ctgtaggaga cagggtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta ccccgtacac ttttggccag 300

gggaccaagc tggagatcaa a 321

<210> 200

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 200

gccatccgga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gactattact gactggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctataag gcgtctactt tagaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgatttcg caacttatta ctgccaacaa tataatagtt attcttgggc gttcggccaa 300

gggaccaagg tggaaatcaa a 321

<210> 201

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 201

gccatccgga tgacccagtt tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gagtattggt agctggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctataag gcgtctagtt tagaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgattttg caacttatta ctgccaacag tataatagtt attctcacac ttttggccaa 300

gggaccaagg tggaaatcaa a 321

<210> 202

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 202

gacatcgtga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc aggcgagtca ggacattagc aactatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctacgat gcatccaatt tggaaacagg ggtcccatca 180

aggttcagtg gaagtggatc tgggacagat tttactttca ccatcagcag cctgcagcct 240

gaagatattg caacatatta ctgtcaacag tatgataatc tccccttatt cactttcggc 300

cctgggacca aagtggatat caaa 324

<210> 203

<211> 336

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 203

gatattgtga tgacccagac tccactctcc ctgcccgtca cccctggaga gtcggcctcc 60

ctctcctgca ggtctagtca gagcctcctg cataggagtg gacacaacta tttggattgg 120

tacctgcaga agccagggca gtctccacag ctcctgattt atttgggttc tattcgggcc 180

tccggggtcc ctgacaggtt cagtggcagt ggatcaggca cagactttac actgaaaata 240

agtagagtgg aggctgagga tgttggggtt tattactgca tgcaaggtct acaacctccg 300

tacacttttg gccaagggac caaggtggaa atcaaa 336

<210> 204

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 204

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag tctgcaacct 240

gaagattttg caacttacta ctgtcaacag agttacagta cccctcgcac ttttggccag 300

gggaccaagc tggagatcaa a 321

<210> 205

<211> 336

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 205

gatattgtga tgactcagcc tccactctcc ctgcccgtca cccctggaga gccggcctcc 60

atctcctgca ggtctagtca gagcctcctc catagtaatg gatacaacta tttggattgg 120

tacctgcaga agccagggca gtctccacag ctcctgatct atttgggttc taatcgggcc 180

tccggggtcc ctgacaggtt cagtggcagt ggatcaggca cagattttac actgaaaatc 240

agcagagtgg aggctgagga tgttggggtt tattactgca tgcaagctct acaaactccg 300

tacacttttg gccaggggac caagctggag atcaaa 336

<210> 206

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 206

gccatccgga tgacccagtc tccttccacc ctgtctgcat ctgtgggcga cagagtcacc 60

atcacttgcc gggccagtca gattattagt gactggttgg cctggtatca gcagagacca 120

ggggaagccc ctaagctcct catctataag gcatctaatt tacaaagtgg ggtcccatca 180

aggttcagcg gcagtgtatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgattttg cgacttatta ctgccaacaa tataatagtg attctgggca cacttttggc 300

caagggacca aggtggaaat caga 324

<210> 207

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 207

gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60

atcacttgtc gggcgagtca gggtattagc agctggttag cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatggt gcatccagtt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttacta ttgtcaacag gctaacagtt tccctcccac tttcggcgga 300

gggaccaagg tggagatcaa a 321

<210> 208

<211> 336

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 208

gatattgtga tgactcagcc tccactctcc ctgcccgtca cccctggaga gccggcctcc 60

atctcctgca ggtctagtca gagcctcctg catagtaatg gatacaacta tttggattgg 120

tacctgcaga agccagggca gtctccacag ctcctgatct atttgggttc taatcgggcc 180

tccggggtcc ctgacaggtt cagtggcagt ggatcaggca cagattttac actgaaaatc 240

agcagagtgg aggctgggga tgttggggtt tattactgca tgcaagctct acaaacccct 300

ttcactttcg gccctgggac caaagtggat atcaaa 336

<210> 209

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 209

gaaatagtga tgacgcagtc tccagacacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtga gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gtagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacccta cacttttggc 300

caagggacca aggtggaaat caaa 324

<210> 210

<211> 339

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 210

gatattgtga tgactcagtc tccactctcc ctgcccgtca cccttggaca gccggcctcc 60

atctcctgca ggtctagtca aagcctcgta cacagtgatg gaaacaccta cttgaattgg 120

tttcagcaga ggccaggcca atctccaagg cgcctaattt ataaggtttc taaccgggac 180

tctggggtcc cagacagatt cagcggcagt gggtcaggca ctgatttcac actgaaaatc 240

agcagggtgg aggctgaaga tgttggggtt tattactgca tgcaaggtac acactggcct 300

ccgaacactt ttggccaagg gaccaaggtg gaaatcaaa 339

<210> 211

<211> 327

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 211

gccatccaga tgacccagtc tccttccacc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gagtattagt agctggttgg cctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctataag gcgtctagtt tagaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagaa ttcactctca ccatcagcag cctgcagcct 240

gatgattttg caacttatta ctgccaacag tataatagtt attctgacat gtacactttt 300

ggccaaggga ccaaggtgga aatcaaa 327

<210> 212

<211> 336

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 212

gatattgtga tgactcagcc tccactctcc ctgcccgtca cccttggaca gccggcctcc 60

atctcctgca ggtctagtca aagcctcgta cacagtgatg gaaacaccta cttgaattgg 120

tttcagcaga ggccaggcca atctccaagg cgcctaattt ataaggtttc taaccgggac 180

tctggggtcc cagacagatt cagcggcagt gggtcaggca ctgatttcac actgaaaatc 240

agcagggtgg aggctgagga tgttggggtt tattactgca tgcaaggtac acactggcct 300

tacacttttg gccaagggac caaggtggaa atcaaa 336

<210> 213

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 213

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accccttcac tttcggccct 300

gggaccaaag tggatatcaa a 321

<210> 214

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 214

gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtgaacag cttaagagtt accctccgta cacttttggc 300

caggggacca agctggagat caaa 324

<210> 215

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 215

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

<210> 216

<211> 239

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 216

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Met Val

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser His

210 215 220

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

225 230 235

<210> 217

<211> 239

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 217

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235

<210> 218

<211> 239

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 218

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val

115 120 125

Thr Val Ser Ser Ala Ile Arg Met Thr Gln Ser Pro Ser Ser Leu Ser

130 135 140

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

145 150 155 160

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

165 170 175

Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser

180 185 190

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

195 200 205

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

210 215 220

Ser Thr Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

225 230 235

<210> 219

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 219

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Asp Ile Ala Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser Ala Ile Arg Met Thr Gln Ser Pro Ser Ser

115 120 125

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

130 135 140

Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys

145 150 155 160

Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Lys

225

<210> 220

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 220

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln

195 200 205

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

210 215 220

Lys

225

<210> 221

<211> 220

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 221

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser Ala Ile Arg Met Thr Gln Ser Pro Ser Ser Val

115 120 125

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

130 135 140

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

145 150 155 160

Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

<210> 222

<211> 228

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 222

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Phe Ala Gln Lys Phe

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Asp Arg Gly Phe Ser Ile Val Ser Tyr Ala Met Asp Val Trp

100 105 110

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

115 120 125

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

130 135 140

Cys Arg Ala Ser Gln Ser Ile Asn Ser Trp Leu Ala Trp Tyr Gln Gln

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Tyr Cys Gln Gln His Asn Ser Tyr Pro Thr Phe Gly Gln Gly Thr Lys

210 215 220

Val Glu Ile Lys

225

<210> 223

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 223

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile

180 185 190

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

195 200 205

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

210 215 220

<210> 224

<211> 235

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 224

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Ser Ala Tyr His Gly Asn Thr Asn Tyr Ala Gln Lys Leu

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

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

85 90 95

Ala Arg Gly Leu Ala Pro Ser Tyr Cys Gly Gly Asp Cys Tyr Pro Arg

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230 235

<210> 225

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 225

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Gly Arg Phe Thr Ile Ser Arg His Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Ser Arg Phe Ser Gly Ser Gly Ser Gly Ala Glu Phe Thr Leu Thr Ile

180 185 190

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

195 200 205

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

210 215 220

Lys

225

<210> 226

<211> 235

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 226

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

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

85 90 95

Ala Arg Gly Leu Ala Pro Ser Tyr Cys Gly Gly Asp Cys Tyr Pro Arg

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Leu Leu

210 215 220

Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

225 230 235

<210> 227

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 227

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile

180 185 190

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

195 200 205

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

210 215 220

Lys

225

<210> 228

<211> 226

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 228

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Gln Glu Arg Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Ile Lys

225

<210> 229

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 229

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Gln Glu Arg Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Thr

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Tyr Gly Asn Tyr Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

210 215 220

<210> 230

<211> 239

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 230

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Gly Ile Ser Trp Asn Ser Gly Ser Ile Gly Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Lys Glu Asp Ala Gly Tyr Tyr Tyr Asp Ser Ser Gly Tyr Tyr Tyr

100 105 110

Pro Lys Ala His Trp Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val

115 120 125

Thr Val Ser Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser

130 135 140

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

145 150 155 160

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

165 170 175

Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235

<210> 231

<211> 230

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 231

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

1 5 10 15

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

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Ser Arg Ser Pro Ser Ile Ala Ala Ala Ala Asn Ala Phe Asp Ile

100 105 110

Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser Asp Ile Val Met Thr

115 120 125

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

130 135 140

Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Tyr Thr Phe Gly Gln Gly

210 215 220

Thr Lys Leu Glu Ile Lys

225 230

<210> 232

<211> 229

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 232

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Phe Ala Gln Lys Phe

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Asp Arg Gly Phe Ser Ile Val Ser Tyr Ala Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ile Arg Met Thr Gln

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser Trp Ala Phe Gly Gln Gly Thr

210 215 220

Lys Val Glu Ile Lys

225

<210> 233

<211> 229

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 233

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

1 5 10 15

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

20 25 30

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

35 40 45

Gly Trp Ile Asn Pro Asn Ser Gly Ala Thr Asn Phe Ala Gln Lys Phe

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Asp Arg Gly Phe Ser Ile Val Ser Tyr Ala Met Asp Val Trp

100 105 110

Gly Gln Gly Thr Thr Val Thr Val Ser Ser Ala Ile Arg Met Thr Gln

115 120 125

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

130 135 140

Cys Arg Ala Ser Gln Ser Ile Gly Ser Trp Leu Ala Trp Tyr Gln Gln

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

Tyr Cys Gln Gln Tyr Asn Ser Tyr Ser His Thr Phe Gly Gln Gly Thr

210 215 220

Lys Val Glu Ile Lys

225

<210> 234

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 234

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Arg Gly Asp Ala Phe Asp Ile Trp Gly Gln Gly Thr Thr Val

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser

180 185 190

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

195 200 205

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

210 215 220

<210> 235

<211> 234

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 235

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

1 5 10 15

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

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

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

115 120 125

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

130 135 140

Cys Arg Ser Ser Gln Ser Leu Leu His Arg Ser Gly His Asn Tyr Leu

145 150 155 160

Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

225 230

<210> 236

<211> 228

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 236

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

1 5 10 15

Thr Leu Ser Leu Thr Cys Ser Val Ser Gly Gly Ser Ile Thr Gln Ile

20 25 30

Ile Tyr Tyr Trp Ala Trp Ile Arg Gln Pro Pro Gly Arg Gly Leu Glu

35 40 45

Trp Ile Gly Ser Ile Tyr Tyr Arg Gly Ser Thr Ser Ser Asn Pro Ser

50 55 60

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

65 70 75 80

Ser Leu Asn Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg Ala Val Arg His Asp Tyr Asn Tyr Phe Asp Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser Asp Ile Gln Leu Thr Gln Ser

115 120 125

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

130 135 140

Arg Ala Ser Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys

145 150 155 160

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

165 170 175

Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

180 185 190

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

195 200 205

Cys Gln Gln Ser Tyr Ser Thr Pro Arg Thr Phe Gly Gln Gly Thr Lys

210 215 220

Leu Glu Ile Lys

225

<210> 237

<211> 234

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 237

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

1 5 10 15

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

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

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

115 120 125

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

130 135 140

Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu

145 150 155 160

Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr

165 170 175

Leu Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser

180 185 190

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

195 200 205

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

210 215 220

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230

<210> 238

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 238

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser Ala Ile Arg Met Thr Gln Ser Pro Ser Thr Leu

115 120 125

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

130 135 140

Ile Ile Ser Asp Trp Leu Ala Trp Tyr Gln Gln Arg Pro Gly Glu Ala

145 150 155 160

Pro Lys Leu Leu Ile Tyr Lys Ala Ser Asn Leu Gln Ser Gly Val Pro

165 170 175

Ser Arg Phe Ser Gly Ser Val Ser Gly Thr Glu Phe Thr Leu Thr Ile

180 185 190

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

195 200 205

Asn Ser Asp Ser Gly His Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

210 215 220

Arg

225

<210> 239

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 239

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

Pro Lys Leu Leu Ile Tyr Gly Ala Ser Ser Leu Gln Ser Gly Val Pro

165 170 175

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

180 185 190

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

195 200 205

Asn Ser Phe Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys

210 215 220

<210> 240

<211> 234

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 240

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

1 5 10 15

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

20 25 30

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

35 40 45

Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Val Gly Lys Arg Gly Val Phe Leu Gly Gly Met Asp Val Trp

100 105 110

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

115 120 125

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

130 135 140

Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr Leu

145 150 155 160

Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr

165 170 175

Leu Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser

180 185 190

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

195 200 205

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

210 215 220

Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

225 230

<210> 241

<211> 226

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 241

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Leu Glu Val Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

Met Val Thr Val Ser Ser Glu Ile Val Met Thr Gln Ser Pro Asp Thr

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Ile Lys

225

<210> 242

<211> 243

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 242

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Glu Phe Thr Phe Ser Asn Ala

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

115 120 125

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

130 135 140

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

145 150 155 160

His Ser Asp Gly Asn Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly

165 170 175

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

180 185 190

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

195 200 205

Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met

210 215 220

Gln Gly Thr His Trp Pro Pro Asn Thr Phe Gly Gln Gly Thr Lys Val

225 230 235 240

Glu Ile Lys

<210> 243

<211> 225

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 243

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser

180 185 190

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

195 200 205

Ser Tyr Ser Asp Met Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile

210 215 220

Lys

225

<210> 244

<211> 242

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 244

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr Val Thr Val

115 120 125

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

130 135 140

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

145 150 155 160

His Ser Asp Gly Asn Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly

165 170 175

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

180 185 190

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

195 200 205

Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met

210 215 220

Gln Gly Thr His Trp Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu

225 230 235 240

Ile Lys

<210> 245

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 245

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Val Ala Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

<210> 246

<211> 226

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 246

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu Leu Glu Val Gly Gly Met Asp Val Trp Gly Gln Gly Thr

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

Ile Lys

225

<210> 247

<211> 672

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 247

caggttcagc tggtgcagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgacatcgtg 360

atgacccagt ctccatcttc cgtgtctgca tctgtaggag acagagtcac catcacttgt 420

cgggcgagtc agggtattag cagctggtta gcctggtatc agcagaaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccagt ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga tttcactctc accatcagca gcctgcagcc tgaagatttt 600

gcaacttact attgtcaaca ggctaacagt ttccctccgg ctttcggccc tgggaccaaa 660

gtggatatca aa 672

<210> 248

<211> 717

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 248

gaggtgcagc tggtggagtc cgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcacaat ggtcaccgtc tcgagtgcca tccagatgac ccagtctcca 420

tcctccctgt ctgcatctgt aggagacaga gtcaccatca cttgccgggc aagtcagagc 480

attagcagct atttaaattg gtatcagcag aaaccaggga aagcccctaa gttcctgatc 540

tatgctgcat ccagtttgca aagtggggtc ccatcaaggt tcagtggcag tggatctggg 600

acagatttca ctctcaccat cagcagtctg caacctgaag attttgcaac ttactactgt 660

caacagagtc acagtacccc gtacactttt ggccaaggga ccaaggtgga aatcaaa 717

<210> 249

<211> 717

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 249

gaggtgcagc tggtggagtc cgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatt tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatgg acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcactgtc tcgagtgaca tcgtgatgac ccagtctcca 420

tcctccctgt ctgcatctgt aggagacaga gtcaccatca cttgccgggc aagtcagagc 480

attagcagct atttaaattg gtatcagcag aaaccaggga aagcccctaa gctcctgatc 540

tatgctgcat ccagtttgca aagtggggtc ccatcaaggt tcagtggcag tggatctggg 600

acagatttca ctctcaccat cagcagtctg caacctgaag attttgcaac ttactactgt 660

caacagagtt acagtacccc tcggacgttc ggccagggga ccaagctgga gatcaaa 717

<210> 250

<211> 717

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 250

caggttcagc tggtgcagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcaccgtc tcgagtgcca tccggatgac ccagtctcca 420

tcctccctgt ctgcatctgt aggagacaga gtcaccatca cttgccgggc aagtcagagc 480

attagcagct atttaaattg gtatcagcag aaaccaggga aagcccctaa gctcctgatc 540

tatgctgcat ccagtttgca aagtggggtc ccatcaaggt tcagtggcag tggatctggg 600

acagatttca ctctcaccat cagcagtctg caacctgaag attttgcaac ttactactgt 660

caacagagtt acagtacccc tcggactttt ggccaaggga ccaaggtgga aatcaaa 717

<210> 251

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 251

gaggtgcaac tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agatctggat 300

atagccgggg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagtgccatc 360

cggatgaccc agtctccatc ctccctgtct gcatctgtag gagacagagt caccatcact 420

tgccgggcaa gtcagagcat tagcagctat ttaaattggt atcagcagaa accagggaaa 480

gcccctaagc tcctgatcta tgctgcatcc agtttgcaaa gtggggtccc atcaaggttc 540

agtggcagtg gatctgggac agatttcact ctcaccatca gcagtctgca acctgaagat 600

tttgcaactt actactgtca acagagttac agtaccccgt acacttttgg ccaggggacc 660

aagctggaga tcaaa 675

<210> 252

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 252

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agacctagta 300

gtctacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgaaattgtg 360

ttgacacagt ctccaggcac cctgtctttg tctccagggg aaagagccac cctctcctgc 420

agggccagtc agagtgttag cagcagctac ttagcctggt accagcagaa acctggccag 480

gctcccaggc tcctcatcta tggtgcatcc agcagggcca ctggcatccc agacaggttc 540

agtggcagtg ggtctgggac agacttcact ctcaccatca gcagactgga gcctgaagat 600

tttgcagtgt attactgtca gcagtatggt agctcctcgt acacttttgg ccaggggacc 660

aagctggaga tcaaa 675

<210> 253

<211> 660

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 253

gaggtgcagc tggtggagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtattcggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgccatccgg 360

atgacccagt ctccatcttc cgtgtctgca tctgtaggag acagagtcac catcacttgt 420

cgggcgagtc agggtattag cagctggtta gcctggtatc agcagaaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccagt ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga tttcactctc accatcagca gcctgcagcc tgaagatttt 600

gcaacttact attgtcaaca ggctgaggct ttcggcggag ggaccaaggt ggagatcaaa 660

<210> 254

<211> 684

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 254

gaggtgcagc tggtggagtc tggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagtgcca tccagttgac ccagtctcct tccaccctgt ctgcatctgt cggagacaga 420

gtcaccatca cttgccgggc cagtcagagt attaattcct ggttggcctg gtatcagcag 480

aaaccaggga aagcccctaa actcctgatc tataaggcgt ctcatttaca aagtggcgtc 540

ccttcaaggt tcagcggcag tggatctggg acagatttca ctcttaccat cagtagcctg 600

cagcctgatg attttgcaat ttattactgc caacagcata attcttatcc gaccttcggc 660

caagggacca aggtggaaat caaa 684

<210> 255

<211> 672

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 255

gaggtgcagc tggtggagac tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgaaattgtg 360

ttgacgcagt ctccatcctt cctgtctgca tctgtaggag acagagtcac catcacttgc 420

cgggccagtc agggcattag cagttattta gcctggtatc agcaagaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccact ttgcaaggtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga attcactctc acaatcagca gcctgcagcc tgaagatttt 600

gcaacttatt actgtcaaca gcttaatagt taccctttca ctttcggcgg agggaccaag 660

gtggagatca aa 672

<210> 256

<211> 705

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 256

gaggtgcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcagcgctt accatggtaa cacaaactat 180

gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240

atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagaggcctg 300

gccccatcat attgtggtgg tgactgctat cctcgggccc catttgacta ctggggccag 360

ggaaccctgg tcaccgtctc gagtgacatc cagttgaccc agtctccatc ctccctgtct 420

gcatctgtag gagacagagt caccatcact tgccgggcaa gtcagagcat tagcagctat 480

ttaaattggt atcagcagaa accagggaaa gcccctaagc tcctgatcta tgctgcatcc 540

agtttgcaaa gtggggtccc atcaaggttc agtggcagtg gatctgggac agatttcact 600

ctcaccatca gcagtctgca acctgaagat tttgcaactt actactgtca acagagttac 660

agtaccccgt acacttttgg ccaggggacc aagctggaga tcaaa 705

<210> 257

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 257

gaggtgcagc tggtgcagtc tggaggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agacacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

tcgtccggta tggacgtctg gggccaaggg accctggtca ccgtctcgag tgccatccag 360

ttgacccagt ctccatcctt cctgtctgca tctgtaggag acagagtcac catcacttgc 420

cgggccagtc agggcattag cagttattta gcctggtatc agcaaaaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccact ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctggggcaga attcactctc acaatcagca gcctgcagcc tgaagatttt 600

gcaacttatt actgtcaaca gcttaatagt taccctccgt acacttttgg ccaagggacc 660

aaggtggaaa tcaaa 675

<210> 258

<211> 705

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 258

gaggtgcagc tggtgcagtc tggagctgag gtgaagaagc ctggggcctc agtgaaggtc 60

tcctgcaagg cttctggtta cacctttacc agctatggta tcagctgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcagcggtt tccacggtaa cacaaactat 180

gcacagaagc tccagggcag agtcaccatg accacagaca catccacgag cacagcctac 240

atggagctga ggagcctgag atctgacgac acggccgtgt attactgtgc gagaggcctg 300

gccccatcat attgtggtgg tgactgctat cctcgggccc catttgacta ctggggccag 360

ggaaccctgg tcaccgtctc gagtgccatc cagttgaccc agtctccatc ctccctgtct 420

gcatctgtag gagacagagt caccatcact tgccgggcaa gtcagagcat tagcagctat 480

ttaaattggt atcagcagaa accagggaaa gcccctaagc tcctgatcta tgctgcatcc 540

agtttgcaaa gtggggtccc atcaaggttc agtggcagtg gatctgggac agatttcact 600

ctcaccatca gcagtctgca acctgaagat tttgcaactt actactgtca acagagttac 660

agtacactcc tcactttcgg cggagggacc aaggtggaga tcaaa 705

<210> 259

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 259

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcggt agcaactaca tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcactt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agacttagtc 300

tactacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgacatcgtg 360

atgacccagt ctccatcctt cctgtctgca tctgtaggag acagagtcac catcacttgc 420

cgggccagtc agggcattag cagttattta gcctggtatc agcaaaaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccact ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga attcactctc acaatcagca gcctgcagcc tgaagatttt 600

gcaacttatt actgtcaaca gcttaatagt taccctccgt acacttttgg ccaagggacc 660

aaggtggaaa tcaaa 675

<210> 260

<211> 678

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 260

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggaat caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggcagatt cagcatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatcttcag 300

gagcgaggcg gtatggacgt ctggggccaa gggaccacgg tcaccgtctc gagtgaaatt 360

gtgttgacgc agtctccagc caccctgtct ttgtctccag gggaaagagc caccctctcc 420

tgcggggcca gtcagagtgt tagcagcagc tacttagcct ggtaccagca gaaacctggc 480

ctggcgccca ggctcctcat ctatgatgca tccagcaggg ccactggcat cccagacagg 540

ttcagtggca gtgggtctgg gacagacttc actctcacca tcagcagact ggagcctgaa 600

gattttgcag tgtattactg tcagcagtat ggtagctcac cgctcacttt cggcggaggg 660

accaaggtgg agatcaaa 678

<210> 261

<211> 673

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 261

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggaat caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggcagatt cagcatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatcttcag 300

gagcgaggcg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagtgacatc 360

cagttgaccc agtctccctc caccctgtct gcatctgtag gagacagagt caccatcact 420

tgccgggcca gtcaggctat tagtaactgg ttggcctggt atcagcagaa accagggaaa 480

gcccctaagc tcctgatcta tgaggcgtct aatttagaaa gtggggtccc atcgaggttc 540

agcggcagtg gttctgggac agaattcact ctcaccatca gcagcctgca gcctgatgat 600

tttgcaactt attactgcca acagtatggt aattattgga cgttcggcca agggaccaag 660

gtggaaatca aag 673

<210> 262

<211> 719

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 262

caggtccagc tggtacagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcaccgtc tcgagtggac atccagttga cccagtctcc 420

atcctccctg tctgcatctg taggagacag agtcaccatc acttgccggg caagtcagag 480

cattagcagc tatttaaatt ggtatcagca gaaaccaggg aaagccccta agctcctgat 540

ctatgctgca tccagtttgc aaagtggggt cccatcaagg ttcagtggca gtggatctgg 600

gacagatttc actctcacca tcagcagtct gcaacctgaa gattttgcaa cttactactg 660

tcaacagagt tacagtaccc ctctgacgtt cggccagggg accaagctgg agatcaaag 719

<210> 263

<211> 692

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 263

gaggtgcagc tggtggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagccgatcc 300

cccagtatag cagcagccgc taatgctttt gatatctggg gccaagggac cacggtcacc 360

gtctcgagtg gacatcgtga tgacccagtc ttcatcctcc ctgtctgcat ctgtaggaga 420

cagggtcacc atcacttgcc gggcaagtca gagcattagc agctatttaa attggtatca 480

gcagaaacca gggaaagccc ctaagctcct gatctatgct gcatccagtt tgcaaagtgg 540

ggtcccatca aggttcagtg gcagtggatc tgggacagat ttcactctca ccatcagcag 600

tctgcaacct gaagattttg caacttacta ctgtcaacag agttacagta ccccgtacac 660

ttttggccag gggaccaagc tggagatcaa ag 692

<210> 264

<211> 688

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 264

caggtgcagc tggtggagtc tggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagtgcca tccggatgac ccagtctcct tccaccctgt ctgcatctgt aggagacaga 420

gtcaccatca cttgccgggc cagtcagact attactgact ggttggcctg gtatcagcag 480

aaaccaggga aagcccctaa gctcctgatc tataaggcgt ctactttaga aagtggggtc 540

ccatcaaggt tcagcggcag tggatctggg acagaattca ctctcaccat cagcagcctg 600

cagcctgatg atttcgcaac ttattactgc caacaatata atagttattc ttgggcgttc 660

ggccaaggga ccaaggtgga aatcaaag 688

<210> 265

<211> 688

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 265

gaggtgcagc tggtggagtc cggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagtgcca tccggatgac ccagtttcct tccaccctgt ctgcatctgt aggagacaga 420

gtcaccatca cttgccgggc cagtcagagt attggtagct ggttggcctg gtatcagcag 480

aaaccaggga aagcccctaa gctcctgatc tataaggcgt ctagtttaga aagtggggtc 540

ccatcaaggt tcagcggcag tggatctggg acagaattca ctctcaccat cagcagcctg 600

cagcctgatg attttgcaac ttattactgc caacagtata atagttattc tcacactttt 660

ggccaaggga ccaaggtgga aatcaaag 688

<210> 266

<211> 674

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 266

caggtccagc tggtgcagtc tgggggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtacag cctctgactt caccgtcagt agcaactaca tgacctgggt ccgccaggct 120

ccagggaagg gactggagtg ggtctcactt atttatcccg gtggtagcac atactacgca 180

gactccctga agggccgatt caccatctcc agagacaatt ccaagaacac gctatacctt 240

caaatgaaca gcctgagagt tgaggacacg gctgtgtatt actgtgcgag agaccggggc 300

gatgcatttg atatctgggg ccaagggacc acggtcaccg tctcgagtgg acatcgtgat 360

gacccagtct ccatcctccc tgtctgcatc tgtaggagac agagtcacca tcacttgcca 420

ggcgagtcag gacattagca actatttaaa ttggtatcag cagaaaccag ggaaagcccc 480

taagctcctg atctacgatg catccaattt ggaaacaggg gtcccatcaa ggttcagtgg 540

aagtggatct gggacagatt ttactttcac catcagcagc ctgcagcctg aagatattgc 600

aacatattac tgtcaacagt atgataatct ccccttattc actttcggcc ctgggaccaa 660

agtggatatc aaag 674

<210> 267

<211> 702

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 267

gaggtgcagc tggtggagtc cgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccgagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aaggcaccct ggtcaccgtc 360

tcgagtgata ttgtgatgac ccagactcca ctctccctgc ccgtcacccc tggagagtcg 420

gcctccctct cctgcaggtc tagtcagagc ctcctgcata ggagtggaca caactatttg 480

gattggtacc tgcagaagcc agggcagtct ccacagctcc tgatttattt gggttctatt 540

cgggcctccg gggtccctga caggttcagt ggcagtggat caggcacaga ctttacactg 600

aaaataagta gagtggaggc tgaggatgtt ggggtttatt actgcatgca aggtctacaa 660

cctccgtaca cttttggcca agggaccaag gtggaaatca aa 702

<210> 268

<211> 684

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 268

caggtgcagc tacaacagtg gggcccagga ctggtgaagc cttcggagac cctgtccctc 60

acctgtagcg tctctggtgg ctccatcacg cagattattt actactgggc ctggatccgc 120

cagcccccag ggagggggct ggagtggatt gggagtatct actatagggg gagcacctcc 180

tccaacccgt ccctcaagag tcgagtcacc atatccgtag acacgtccaa gaaccagttc 240

tccctgaacc taacctctgt gaccgccgca gacacggctg tgtattactg tgcgagggcg 300

gttagacatg actacaacta ttttgactac tggggccagg gaaccctggt caccgtctcg 360

agtgacatcc agttgaccca gtctccatcc tccctgtctg catctgtagg agacagagtc 420

accatcactt gccgggcaag tcagagcatt agcagctatt taaattggta tcagcagaaa 480

ccagggaaag cccctaagct cctgatctat gctgcatcca gtttgcaaag tggggtccca 540

tcaaggttca gtggcagtgg atctgggaca gatttcactc tcaccatcag cagtctgcaa 600

cctgaagatt ttgcaactta ctactgtcaa cagagttaca gtacccctcg cacttttggc 660

caggggacca agctggagat caaa 684

<210> 269

<211> 702

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 269

gaggtgcagc tgttggagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aagggaccct ggtcaccgtc 360

tcgagtgata ttgtgatgac tcagcctcca ctctccctgc ccgtcacccc tggagagccg 420

gcctccatct cctgcaggtc tagtcagagc ctcctccata gtaatggata caactatttg 480

gattggtacc tgcagaagcc agggcagtct ccacagctcc tgatctattt gggttctaat 540

cgggcctccg gggtccctga caggttcagt ggcagtggat caggcacaga ttttacactg 600

aaaatcagca gagtggaggc tgaggatgtt ggggtttatt actgcatgca agctctacaa 660

actccgtaca cttttggcca ggggaccaag ctggagatca aa 702

<210> 270

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 270

gaggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggagt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gcggtaccac atactacgca 180

gactccgtga agggcagatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gctgtgtatt actgtgcgag agatctgggg 300

ccatacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgccatccgg 360

atgacccagt ctccttccac cctgtctgca tctgtgggcg acagagtcac catcacttgc 420

cgggccagtc agattattag tgactggttg gcctggtatc agcagagacc aggggaagcc 480

cctaagctcc tcatctataa ggcatctaat ttacaaagtg gggtcccatc aaggttcagc 540

ggcagtgtat ctgggacaga attcactctc accatcagca gcctgcagcc tgatgatttt 600

gcgacttatt actgccaaca atataatagt gattctgggc acacttttgg ccaagggacc 660

aaggtggaaa tcaga 675

<210> 271

<211> 672

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 271

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgacatccag 360

atgacccagt ctccatcttc cgtgtctgca tctgtaggag acagagtcac catcacttgt 420

cgggcgagtc agggtattag cagctggtta gcctggtatc agcagaaacc agggaaagcc 480

cctaagctcc tgatctatgg tgcatccagt ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga tttcactctc accatcagca gcctgcagcc tgaagatttt 600

gcaacttact attgtcaaca ggctaacagt ttccctccca ctttcggcgg agggaccaag 660

gtggagatca aa 672

<210> 272

<211> 702

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 272

gaagtgcagc tggtggagtc tgggggaggc gtggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cgtctggatt caccttcagt acctatgcta tgcactgggt ccgccaggct 120

ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaagtaa taaatactac 180

gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240

ctgcaaatga acagcctgag agctgaggac acggctgtgt attactgtgc gagagtagga 300

aaaagggggg ttttcctggg gggtatggac gtctggggcc aagggaccct ggtcaccgtc 360

tcgagtgata ttgtgatgac tcagcctcca ctctccctgc ccgtcacccc tggagagccg 420

gcctccatct cctgcaggtc tagtcagagc ctcctgcata gtaatggata caactatttg 480

gattggtacc tgcagaagcc agggcagtct ccacagctcc tgatctattt gggttctaat 540

cgggcctccg gggtccctga caggttcagt ggcagtggat caggcacaga ttttacactg 600

aaaatcagca gagtggaggc tggggatgtt ggggtttatt actgcatgca agctctacaa 660

acccctttca ctttcggccc tgggaccaaa gtggatatca aa 702

<210> 273

<211> 678

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 273

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctctta 300

gaagtagggg gtatggacgt ctggggccaa gggacaatgg tcaccgtctc gagtgaaata 360

gtgatgacgc agtctccaga caccctgtct ttgtctccag gggaaagagc caccctctcc 420

tgcagggcca gtgagagtgt tagcagcagc tacttagcct ggtaccagca gaaacctggc 480

caggctccca ggctcctcat ctatggtgca tccagtaggg ccactggcat cccagacagg 540

ttcagtggca gtgggtctgg gacagacttc actctcacca tcagcagact ggagcctgaa 600

gattttgcag tgtattactg tcagcagtat ggtagctcac cctacacttt tggccaaggg 660

accaaggtgg aaatcaaa 678

<210> 274

<211> 729

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 274

gaggtgcaac tggtggagtc tgggggaggc ttggtaaagc ctggggggtc ccttagactc 60

tcctgtgcag cctctgagtt cactttcagt aacgcctgga tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggttggccgt attaaaagca aaactgatgg tgggacaaca 180

gactacgctg cacccgtgaa aggcagattc accatctcaa gagatgattc aaaaaacacg 240

ctgtatctgc aaatgaacag cctgaaaacc gaggacacag ccgtgtatta ctgtaccaca 300

gatcaaccgg agggatacta tggttcgggg agtgtctact actacggtat ggacgtctgg 360

ggccaaggga ccacggtcac cgtctcgagt gatattgtga tgactcagtc tccactctcc 420

ctgcccgtca cccttggaca gccggcctcc atctcctgca ggtctagtca aagcctcgta 480

cacagtgatg gaaacaccta cttgaattgg tttcagcaga ggccaggcca atctccaagg 540

cgcctaattt ataaggtttc taaccgggac tctggggtcc cagacagatt cagcggcagt 600

gggtcaggca ctgatttcac actgaaaatc agcagggtgg aggctgaaga tgttggggtt 660

tattactgca tgcaaggtac acactggcct ccgaacactt ttggccaagg gaccaaggtg 720

gaaatcaaa 729

<210> 275

<211> 675

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 275

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcttgtgcag cctctggggt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaatac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag gactttatat 300

gatgcttttg atatctgggg ccaagggacc acggtcaccg tctcgagtgc catccagatg 360

acccagtctc cttccaccct gtctgcatct gtaggagaca gagtcaccat cacttgccgg 420

gccagtcaga gtattagtag ctggttggcc tggtatcagc agaaaccagg gaaagcccct 480

aagctcctga tctataaggc gtctagttta gaaagtgggg tcccatcaag gttcagcggc 540

agtggatctg ggacagaatt cactctcacc atcagcagcc tgcagcctga tgattttgca 600

acttattact gccaacagta taatagttat tctgacatgt acacttttgg ccaagggacc 660

aaggtggaaa tcaaa 675

<210> 276

<211> 726

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 276

gaggtgcaac tggtggagtc tgggggaggc ttggtaaagc ctggggggtc ccttagactc 60

tcctgtgcag cctctggatt cactttcagt aacgcctgga tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggttggccgt attaaaagca aaactgatgg tgggacaaca 180

gactacgctg cacccgtgaa aggcagattc accatctcaa gagatgattc aaaaaacacg 240

ctgtatctgc aaatgaacag cctgaaaacc gaggacacag ccgtgtatta ctgtaccaca 300

gatcaaccgg agggatacta tggttcgggg agtgtctact actacggtat ggacgtctgg 360

ggccaaggga ccacggtcac cgtctcgagt gatattgtga tgactcagcc tccactctcc 420

ctgcccgtca cccttggaca gccggcctcc atctcctgca ggtctagtca aagcctcgta 480

cacagtgatg gaaacaccta cttgaattgg tttcagcaga ggccaggcca atctccaagg 540

cgcctaattt ataaggtttc taaccgggac tctggggtcc cagacagatt cagcggcagt 600

gggtcaggca ctgatttcac actgaaaatc agcagggtgg aggctgagga tgttggggtt 660

tattactgca tgcaaggtac acactggcct tacacttttg gccaagggac caaggtggaa 720

atcaaa 726

<210> 277

<211> 672

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 277

caggtgcagc tggtggagtc tgggggaggc ttggtccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctggatt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc tgaggacacg gctgtgtatt actgtgcgag agatctcgtt 300

gcctacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgacatccag 360

ttgacccagt ctccatcctc cctgtctgca tctgtaggag acagagtcac catcacttgc 420

cgggccagtc agggcattag cagttattta gcctggtatc agcaaaaacc agggaaagcc 480

cctaagctcc tgatctatgc tgcatccact ttgcaaagtg gggtcccatc aaggttcagc 540

ggcagtggat ctgggacaga tttcactctc accatcagca gcctgcagcc tgaagatttt 600

gcaacttatt actgtcaaca gcttaatagt taccccttca ctttcggccc tgggaccaaa 660

gtggatatca aa 672

<210> 278

<211> 678

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 278

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctctta 300

gaagtagggg gtatggacgt ctggggccaa gggaccctgg tcaccgtctc gagtgacatc 360

cagatgaccc agtctccatc ctccctgtct gcatctgtag gagacagagt caccatcact 420

tgccgggcca gtcagggcat tagcagttat ttagcctggt atcagcaaaa accagggaaa 480

gcccctaagc tcctgatcta tgctgcatcc actttgcaaa gtggggtccc atcaaggttc 540

agcggcagtg gatctgggac agatttcact ctcaccatca gcagcctgca gcctgaagat 600

tttgcaactt attactgtga acagcttaag agttaccctc cgtacacttt tggccagggg 660

accaagctgg agatcaaa 678

<210> 279

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 279

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu His Val Val Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr

100 105 110

Thr Val Thr Val Ser Ser

115

<210> 280

<211> 116

<212> PRT

<213> VH(Artificial Sequence)

<400> 280

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Thr Ser Arg Arg Gly Arg Asp Tyr Trp Gly Gln Gly Thr Met Val

100 105 110

Thr Val Ser Ser

115

<210> 281

<211> 118

<212> PRT

<213> VH(Artificial Sequence)

<400> 281

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Asp Leu His Val Val Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 282

<211> 116

<212> PRT

<213> VH(Artificial Sequence)

<400> 282

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Thr Ser Arg Arg Gly Arg Asp Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser

115

<210> 283

<211> 123

<212> PRT

<213> VH(Artificial Sequence)

<400> 283

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Ile Leu Gly Val Asp Thr Ala Pro Ser Trp Gly Met Asp Val

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 284

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 284

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 285

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 285

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 286

<211> 117

<212> PRT

<213> VH(Artificial Sequence)

<400> 286

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Val Thr Val Ser Ser

115

<210> 287

<211> 126

<212> PRT

<213> VH(Artificial Sequence)

<400> 287

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 288

<211> 126

<212> PRT

<213> VH(Artificial Sequence)

<400> 288

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser

115 120 125

<210> 289

<211> 126

<212> PRT

<213> VH(Artificial Sequence)

<400> 289

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

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

115 120 125

<210> 290

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 290

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105

<210> 291

<211> 113

<212> PRT

<213> VL(Artificial Sequence)

<400> 291

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

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu Asp Ser

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln

85 90 95

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

100 105 110

Lys

<210> 292

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 292

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 293

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 293

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr Asn Tyr Pro Trp

85 90 95

Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105

<210> 294

<211> 112

<212> PRT

<213> VL(Artificial Sequence)

<400> 294

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

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

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

35 40 45

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

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

Leu Gln Thr Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 295

<211> 110

<212> PRT

<213> VL(Artificial Sequence)

<400> 295

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Arg Met Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

100 105 110

<210> 296

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 296

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 297

<211> 106

<212> PRT

<213> VL(Artificial Sequence)

<400> 297

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 298

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 298

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 299

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 299

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Gln

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 300

<211> 107

<212> PRT

<213> VL(Artificial Sequence)

<400> 300

Ala Ile Arg Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Val Ala Thr Tyr Tyr Cys Gln Asn Tyr Asn Ser Ala Pro Phe

85 90 95

Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

100 105

<210> 301

<211> 108

<212> PRT

<213> VL(Artificial Sequence)

<400> 301

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

Arg Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 302

<211> 109

<212> PRT

<213> VL(Artificial Sequence)

<400> 302

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

Pro Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 303

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 303

Gly Phe Thr Phe Ser Ser Tyr Glu

1 5

<210> 304

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 304

Gly Tyr Ser Phe Thr Ser Tyr Trp

1 5

<210> 305

<211> 8

<212> PRT

<213> VH_CDR1(Artificial Sequence)

<400> 305

Gly Phe Thr Val Ser Arg Asn Tyr

1 5

<210> 306

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 306

Ile Ser Ser Ser Gly Ser Thr Ile

1 5

<210> 307

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 307

Ile Asp Pro Ser Asp Ser Tyr Thr

1 5

<210> 308

<211> 8

<212> PRT

<213> VH_CDR2(Artificial Sequence)

<400> 308

Ile Tyr Pro Gly Asp Ser Asp Thr

1 5

<210> 309

<211> 12

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 309

Ala Arg Asp Leu His Val Val Gly Ala Phe Asp Ile

1 5 10

<210> 310

<211> 9

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 310

Ala Thr Ser Arg Arg Gly Arg Asp Tyr

1 5

<210> 311

<211> 16

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 311

Ala Arg Ile Leu Gly Val Asp Thr Ala Pro Ser Trp Gly Met Asp Val

1 5 10 15

<210> 312

<211> 19

<212> PRT

<213> VH_CDR3(Artificial Sequence)

<400> 312

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

1 5 10 15

Phe Asp Ile

<210> 313

<211> 7

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 313

Gln Ser Val Ser Ser Ser Tyr

1 5

<210> 314

<211> 12

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 314

Gln Ser Leu Leu Asp Ser Asp Asp Gly Asn Thr Tyr

1 5 10

<210> 315

<211> 6

<212> PRT

<213> VL_CDR1(Artificial Sequence)

<400> 315

Gln Gly Ile Ser Asn Tyr

1 5

<210> 316

<211> 3

<212> PRT

<213> VL_CDR2(Artificial Sequence)

<400> 316

Thr Leu Ser

<210> 317

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 317

Gln Gln Tyr Gly Ser Ser Pro Asp Thr

1 5

<210> 318

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 318

Met Gln Arg Ile Glu Phe Pro Tyr Thr

1 5

<210> 319

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 319

Leu Gln Asp Tyr Asn Tyr Pro Trp Thr

1 5

<210> 320

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 320

Met Gln Ala Leu Gln Thr Pro Trp Thr

1 5

<210> 321

<211> 11

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 321

Gln Gln Tyr Gly Ser Ser Pro Arg Met Tyr Thr

1 5 10

<210> 322

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 322

Gln Gln Leu Asn Ser Tyr Pro Tyr Thr

1 5

<210> 323

<211> 8

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 323

Gln Gln Leu Asn Ser Tyr Pro Gly

1 5

<210> 324

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 324

Gln Gln Leu Asn Ser Tyr Pro Gln Thr

1 5

<210> 325

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 325

Gln Asn Tyr Asn Ser Ala Pro Phe Thr

1 5

<210> 326

<211> 9

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 326

Gln Gln Tyr Gly Ser Ser Pro Arg Thr

1 5

<210> 327

<211> 10

<212> PRT

<213> VL_CDR3(Artificial Sequence)

<400> 327

Gln Gln Tyr Gly Ser Ser Pro Pro Phe Thr

1 5 10

<210> 328

<211> 396

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 328

caggtccagc tggtacagtc tgggggaggc ttggtacagc ctggcaggtc cctgagactc 60

tcctgtgcag cctctggatt cacctttgat gattatgcca tgcactgggt ccggcaagct 120

ccagggaagg gcctggagtg ggtctcaggt attagttgga atagtggtag cataggctat 180

gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240

ctgcaaatga acagtctgag agctgaggac acggccttgt attactgtgc aaaagaggat 300

gcggggtatt actatgatag tagtggttat tactacccta aagcccactg gtacttcgat 360

ctctggggcc gtggcaccct ggtcaccgtc tcgagt 396

<210> 329

<211> 366

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 329

gaggtgcagc tggtggagtc cggggctgag gtgaagaagc ctggggcctc agtgaaagtc 60

tcctgcaagg cttctggata caccttcacc ggttactata tccactgggt gcgacaggcc 120

cctggacaag ggcttgagtg gatgggatgg atcaacccta acagtggtgc cacaaacttt 180

gcacagaagt ttcggggcag ggtcaccatg accagggaca cctccatcac cacagcctac 240

atggagatga gcaggctgat atctgacgac acggccgtgt atttctgtgc gagagatcga 300

ggcttcagta tcgtatccta cgctatggac gtctggggcc aagggaccac ggtcaccgtc 360

tcgagt 366

<210> 330

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 330

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctgcat 300

gtggtgggtg cttttgatat ctggggccaa gggaccacgg tcaccgtctc gagt 354

<210> 331

<211> 348

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 331

caggtccagc tggtacagtc tgggggaggc ttggtacagc ctggagggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agttatgaaa tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagtac catatactac 180

gcagactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240

ctgcaaatga acagcctgag agccgaggac acggctgttt attactgtgc gaccagccgt 300

cgcggacggg actactgggg ccagggcaca atggtcaccg tctcgagt 348

<210> 332

<211> 354

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 332

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctgcat 300

gtggtgggtg cttttgatat ctggggccaa gggaccctgg tcaccgtctc gagt 354

<210> 333

<211> 348

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 333

gaggtgcagc tggtggagtc tgggggaggc ttggtacggc ctggagggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agttatgaaa tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagcac catatactac 180

gcagactctg tgaagggccg attcaccatc tccagagaca acgccaaaaa ctcactgtat 240

ctgcaaatga acagcctgag agccgaggac acggctgttt attactgtgc gaccagccgt 300

cgcggacggg actactgggg ccagggcacc ctggtcaccg tctcgagt 348

<210> 334

<211> 369

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 334

gaggtgcagc tggtgcagtc tggagcagag gtgaaaaagc ccggggagtc tctgaggatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcagctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatggggagg attgatccta gtgactctta taccaactac 180

agcccgtcct tccaaggcca cgtcaccatc tcagctgaca agtccatcag cactgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagaatttta 300

ggggtggata cagctccctc ttggggtatg gacgtctggg gccaagggac cctggtcacc 360

gtctcgagt 369

<210> 335

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 335

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg gactggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 336

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 336

gaggtgcagc tggtggagac tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 337

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 337

caggtgcagc tggtgcagtc tgggggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 338

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 338

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggtcaaggg accacggtca ccgtctcgag t 351

<210> 339

<211> 351

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 339

gaggtgcagc tgttggagtc tgggggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag t 351

<210> 340

<211> 378

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 340

caggtgcagc tggtgcaatc tggggcagag gtgaaaaagc ccggggagtc tctgaagatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcggctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatggggatc atctatcctg gtgactctga taccagatac 180

agcccgtcct tccaaggcca ggtcatcatc tcagccgaca agtccatcag caccgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagccgagac 300

ccaattatag cacaaggacg gacaatgttc gatgcttttg atatctgggg ccaagggaca 360

atggtcaccg tctcgagt 378

<210> 341

<211> 378

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 341

caaatgcagc tggtgcagtc tggggcagag gtgaaaaagc ccggggagtc tctgaagatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcggctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatggggatc atctatcctg gtgactctga taccagatac 180

agcccgtcct tccaaggcca ggtcaccatc tcagccgaca agtccatcag caccgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagccgagac 300

ccaattatag cacaaggacg gacaatgttc gatgcttttg atatctgggg ccaggggaca 360

atggtcaccg tctcgagt 378

<210> 342

<211> 378

<212> DNA

<213> VH_DNA(Artificial Sequence)

<400> 342

caggtccagc tggtacagtc tggggcagag gtgaaaaagc ccggggagtc tctgaagatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcggctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatgggggtc atctatcctg gtgactctga taccagatac 180

agcccgtcct tccaaggcca ggtcaccatc tcagccgaca agtccatcag caccgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagccgagac 300

ccaattatag cacaaggacg gacaatgttc gatgcttttg atatctgggg ccaagggacc 360

ctggtcaccg tctcgagt 378

<210> 343

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 343

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggcgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccaga cacttttggc 300

caggggacca agctggagat caaa 324

<210> 344

<211> 339

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 344

gatattgtga tgacccagac tccactctcc ctgcccgtca cccctggaga gccggcctcc 60

atctcctgca ggtctagtca gagcctcttg gatagtgatg atggaaacac ctatttggac 120

tggtacctgc agaagccagg gcagtctcca cagctcctga tctatacgct ttcctatcgg 180

gcctctggag tcccagacag gttcagtggc agtgggtcag gcactgattt cacactgaaa 240

atcagcaggg tggaggctga ggatgttgga gtttattact gcatgcaacg tatagagttt 300

ccctacactt ttggccaggg gaccaagctg gagatcaaa 339

<210> 345

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 345

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctta cacttttggc 300

caagggacca aggtggaaat caaa 324

<210> 346

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 346

gatattgtga tgacccagac tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcaagtca gggcattaga aatgatttag gctggtatca gcagaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccagtt tacaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tggcacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtctacaa gattacaatt acccgtggac gttcggccaa 300

gggaccaagg tggaaatcaa a 321

<210> 347

<211> 336

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 347

gatattgtga tgactcagcc tccactctcc ctgcccgtca cccctggaga gccggcctcc 60

atctcctgca ggtctagtca gagcctcctg catagtaatg gatacaacta tttggattgg 120

tacctgcaga agccagggca gtctccacag ctcctgatct atttgggttc taatcgggcc 180

tccggggtcc ctgacaggtt cagtggcagt ggatcaggca cagattttac actgaaaatc 240

agcagagtgg aggctgagga tgttggggtt tattactgca tgcaagctct acaaactccg 300

tggacgttcg gccaggggac caagctggag atcaaa 336

<210> 348

<211> 330

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 348

gaaattgtgt tgacacagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccacg aatgtacact 300

tttggccaag ggaccaaggt ggaaatcaaa 330

<210> 349

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 349

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt acccgtacac ttttggccag 300

gggaccaagc tggagatcaa a 321

<210> 350

<211> 318

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 350

gacatcgtga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accccggttt cggccctggg 300

accaaagtgg atatcaaa 318

<210> 351

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 351

gacatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accctttcac tttcggccag 300

gggaccaagc tggagatcaa a 321

<210> 352

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 352

gccatccagt tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggccagtca gggcattagc agttatttag cctggtatca gcaaaaacca 120

gggaaagccc ctaagctcct gatctatgct gcatccactt tgcaaagtgg ggtcccatca 180

aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagattttg caacttatta ctgtcaacag cttaatagtt accctcaaac gttcggccag 300

gggaccaagc tggagatcaa a 321

<210> 353

<211> 321

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 353

gccatccgga tgacccagtc tccatcctcc ctgtctgcat ctgtaggaga cagagtcacc 60

atcacttgcc gggcgagtca gggcattagc aattatttag cctggtatca gcagaaacca 120

gggaaagttc ctaagctcct gatctatgct gcatccactt tgcaatcagg ggtcccatct 180

cggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240

gaagatgttg caacttatta ctgtcaaaac tataacagtg cccccttcac tttcggccct 300

gggaccaaag tggatatcaa a 321

<210> 354

<211> 324

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 354

gaaattgtgt tgacacagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcaccgag aacgttcggc 300

caggggacca agctggagat caaa 324

<210> 355

<211> 327

<212> DNA

<213> VL_DNA(Artificial Sequence)

<400> 355

gaaattgtgt tgacgcagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60

ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120

cctggccagg ctcccaggct cctcatctat ggtgcatcca gcagggccac tggcatccca 180

gacaggttca gtggcagtgg gtctgggaca gacttcactc tcaccatcag cagactggag 240

cctgaagatt ttgcagtgta ttactgtcag cagtatggta gctcacctcc attcactttc 300

ggccagggga ccaagctgga gatcaaa 327

<210> 356

<211> 226

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 356

Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn

20 25 30

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Arg Asp Leu His Val Val Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr

100 105 110

Thr Val Thr Val Ser Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr

115 120 125

Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser

130 135 140

Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly

145 150 155 160

Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly

165 170 175

Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

180 185 190

Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln

195 200 205

Gln Tyr Gly Ser Ser Pro Asp Thr Phe Gly Gln Gly Thr Lys Leu Glu

210 215 220

Ile Lys

225

<210> 357

<211> 229

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 357

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Glu Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Thr Ser Arg Arg Gly Arg Asp Tyr Trp Gly Gln Gly Thr Met Val

100 105 110

Thr Val Ser Ser Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Pro

115 120 125

Val Thr Pro Gly Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser

130 135 140

Leu Leu Asp Ser Asp Asp Gly Asn Thr Tyr Leu Asp Trp Tyr Leu Gln

145 150 155 160

Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Thr Leu Ser Tyr Arg

165 170 175

Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp

180 185 190

Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr

195 200 205

Tyr Cys Met Gln Arg Ile Glu Phe Pro Tyr Thr Phe Gly Gln Gly Thr

210 215 220

Lys Leu Glu Ile Lys

225

<210> 358

<211> 226

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 358

Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Ser Asn

20 25 30

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Arg Asp Leu His Val Val Gly Ala Phe Asp Ile Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr

115 120 125

Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser

130 135 140

Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly

145 150 155 160

Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly

165 170 175

Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu

180 185 190

Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln

195 200 205

Gln Tyr Gly Ser Ser Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu

210 215 220

Ile Lys

225

<210> 359

<211> 223

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 359

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Arg Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Glu Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Tyr Ile Ser Ser Ser Gly Ser Thr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Thr Ser Arg Arg Gly Arg Asp Tyr Trp Gly Gln Gly Thr Leu Val

100 105 110

Thr Val Ser Ser Asp Ile Val Met Thr Gln Thr Pro Ser Ser Leu Ser

115 120 125

Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly

130 135 140

Ile Arg Asn Asp Leu Gly Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro

145 150 155 160

Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser

165 170 175

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser

180 185 190

Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Leu Gln Asp Tyr

195 200 205

Asn Tyr Pro Trp Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys

210 215 220

<210> 360

<211> 235

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 360

Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Arg Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Ser Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Arg Ile Asp Pro Ser Asp Ser Tyr Thr Asn Tyr Ser Pro Ser Phe

50 55 60

Gln Gly His Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Arg Ile Leu Gly Val Asp Thr Ala Pro Ser Trp Gly Met Asp Val

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Asp Ile Val Met Thr

115 120 125

Gln Pro Pro Leu Ser Leu Pro Val Thr Pro Gly Glu Pro Ala Ser Ile

130 135 140

Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser Asn Gly Tyr Asn Tyr

145 150 155 160

Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile

165 170 175

Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly

180 185 190

Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala

195 200 205

Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala Leu Gln Thr Pro Trp

210 215 220

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230 235

<210> 361

<211> 227

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 361

Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Arg Asn

20 25 30

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu

115 120 125

Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln

130 135 140

Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

145 150 155 160

Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile

165 170 175

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

180 185 190

Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln

195 200 205

Tyr Gly Ser Ser Pro Arg Met Tyr Thr Phe Gly Gln Gly Thr Lys Val

210 215 220

Glu Ile Lys

225

<210> 362

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 362

Glu Val Gln Leu Val Glu Thr Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Arg Asn

20 25 30

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu

115 120 125

Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln

130 135 140

Gly Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala

145 150 155 160

Pro Lys Leu Leu Ile Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro

165 170 175

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

180 185 190

Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu

195 200 205

Asn Ser Tyr Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

210 215 220

<210> 363

<211> 223

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 363

Gln Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Arg Asn

20 25 30

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Asp Ile Val Met Thr Gln Ser Pro Ser Ser Leu

115 120 125

Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln

130 135 140

Gly Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala

145 150 155 160

Pro Lys Leu Leu Ile Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro

165 170 175

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

180 185 190

Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu

195 200 205

Asn Ser Tyr Pro Gly Phe Gly Pro Gly Thr Lys Val Asp Ile Lys

210 215 220

<210> 364

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 364

Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Arg Asn

20 25 30

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu

115 120 125

Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln

130 135 140

Gly Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala

145 150 155 160

Pro Lys Leu Leu Ile Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro

165 170 175

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

180 185 190

Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu

195 200 205

Asn Ser Tyr Pro Phe Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

210 215 220

<210> 365

<211> 224

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 365

Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Ile Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Arg Asn

20 25 30

Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val

35 40 45

Ser Val Ile Tyr Ser Gly Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys

50 55 60

Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu

65 70 75 80

Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala

85 90 95

Arg Asp Leu Val Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr Thr

100 105 110

Val Thr Val Ser Ser Ala Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu

115 120 125

Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln

130 135 140

Gly Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala

145 150 155 160

Pro Lys Leu Leu Ile Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro

165 170 175

Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile

180 185 190

Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu

195 200 205

Asn Ser Tyr Pro Gln Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

210 215 220

<210> 366

<211> 233

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 366

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Ile Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Ala Ile

115 120 125

Arg Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg

130 135 140

Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Asn Tyr Leu Ala

145 150 155 160

Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile Tyr Ala

165 170 175

Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly

180 185 190

Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp

195 200 205

Val Ala Thr Tyr Tyr Cys Gln Asn Tyr Asn Ser Ala Pro Phe Thr Phe

210 215 220

Gly Pro Gly Thr Lys Val Asp Ile Lys

225 230

<210> 367

<211> 234

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 367

Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Glu Ile

115 120 125

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

130 135 140

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu

145 150 155 160

Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

165 170 175

Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

180 185 190

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu

195 200 205

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Arg Thr

210 215 220

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230

<210> 368

<211> 235

<212> PRT

<213> VH_VL(Artificial Sequence)

<400> 368

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu

1 5 10 15

Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Ser Phe Thr Ser Tyr

20 25 30

Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Trp Met

35 40 45

Gly Val Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe

50 55 60

Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr

65 70 75 80

Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys

85 90 95

Ala Ser Arg Asp Pro Ile Ile Ala Gln Gly Arg Thr Met Phe Asp Ala

100 105 110

Phe Asp Ile Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Glu Ile

115 120 125

Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg

130 135 140

Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu

145 150 155 160

Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

165 170 175

Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser

180 185 190

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu

195 200 205

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Pro Phe

210 215 220

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

225 230 235

<210> 369

<211> 678

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 369

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctgcat 300

gtggtgggtg cttttgatat ctggggccaa gggaccacgg tcaccgtctc gagtgaaatt 360

gtgttgacgc agtctccagg caccctgtct ttgtctccag gggaaagagc caccctctcc 420

tgcagggcca gtcagagtgt tagcagcagc tacttagcct ggtaccagca gaaacctggc 480

caggctccca ggctcctcat ctatggcgca tccagcaggg ccactggcat cccagacagg 540

ttcagtggca gtgggtctgg gacagacttc actctcacca tcagcagact ggagcctgaa 600

gattttgcag tgtattactg tcagcagtat ggtagctcac cagacacttt tggccagggg 660

accaagctgg agatcaaa 678

<210> 370

<211> 687

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 370

caggtccagc tggtacagtc tgggggaggc ttggtacagc ctggagggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agttatgaaa tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagtac catatactac 180

gcagactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctcactgtat 240

ctgcaaatga acagcctgag agccgaggac acggctgttt attactgtgc gaccagccgt 300

cgcggacggg actactgggg ccagggcaca atggtcaccg tctcgagtga tattgtgatg 360

acccagactc cactctccct gcccgtcacc cctggagagc cggcctccat ctcctgcagg 420

tctagtcaga gcctcttgga tagtgatgat ggaaacacct atttggactg gtacctgcag 480

aagccagggc agtctccaca gctcctgatc tatacgcttt cctatcgggc ctctggagtc 540

ccagacaggt tcagtggcag tgggtcaggc actgatttca cactgaaaat cagcagggtg 600

gaggctgagg atgttggagt ttattactgc atgcaacgta tagagtttcc ctacactttt 660

ggccagggga ccaagctgga gatcaaa 687

<210> 371

<211> 678

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 371

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt agcaactaca tgagctgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctgcat 300

gtggtgggtg cttttgatat ctggggccaa gggaccctgg tcaccgtctc gagtgaaatt 360

gtgttgacgc agtctccagg caccctgtct ttgtctccag gggaaagagc caccctctcc 420

tgcagggcca gtcagagtgt tagcagcagc tacttagcct ggtaccagca gaaacctggc 480

caggctccca ggctcctcat ctatggtgca tccagcaggg ccactggcat cccagacagg 540

ttcagtggca gtgggtctgg gacagacttc actctcacca tcagcagact ggagcctgaa 600

gattttgcag tgtattactg tcagcagtat ggtagctcac cttacacttt tggccaaggg 660

accaaggtgg aaatcaaa 678

<210> 372

<211> 669

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 372

gaggtgcagc tggtggagtc tgggggaggc ttggtacggc ctggagggtc cctgagactc 60

tcctgtgcag cctctggatt caccttcagt agttatgaaa tgaactgggt ccgccaggct 120

ccagggaagg ggctggagtg ggtttcatac attagtagta gtggtagcac catatactac 180

gcagactctg tgaagggccg attcaccatc tccagagaca acgccaaaaa ctcactgtat 240

ctgcaaatga acagcctgag agccgaggac acggctgttt attactgtgc gaccagccgt 300

cgcggacggg actactgggg ccagggcacc ctggtcaccg tctcgagtga tattgtgatg 360

acccagactc catcctccct gtctgcatct gtaggagaca gagtcaccat cacttgccgg 420

gcaagtcagg gcattagaaa tgatttaggc tggtatcagc agaaaccagg gaaagcccct 480

aagctcctga tctatgctgc atccagttta caaagtgggg tcccatcaag gttcagcggc 540

agtggatctg gcacagattt cactctcacc atcagcagcc tgcagcctga agattttgca 600

acttattact gtctacaaga ttacaattac ccgtggacgt tcggccaagg gaccaaggtg 660

gaaatcaaa 669

<210> 373

<211> 705

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 373

gaggtgcagc tggtgcagtc tggagcagag gtgaaaaagc ccggggagtc tctgaggatc 60

tcctgtaagg gttctggata cagctttacc agctactgga tcagctgggt gcgccagatg 120

cccgggaaag gcctggagtg gatggggagg attgatccta gtgactctta taccaactac 180

agcccgtcct tccaaggcca cgtcaccatc tcagctgaca agtccatcag cactgcctac 240

ctgcagtgga gcagcctgaa ggcctcggac accgccatgt attactgtgc gagaatttta 300

ggggtggata cagctccctc ttggggtatg gacgtctggg gccaagggac cctggtcacc 360

gtctcgagtg atattgtgat gactcagcct ccactctccc tgcccgtcac ccctggagag 420

ccggcctcca tctcctgcag gtctagtcag agcctcctgc atagtaatgg atacaactat 480

ttggattggt acctgcagaa gccagggcag tctccacagc tcctgatcta tttgggttct 540

aatcgggcct ccggggtccc tgacaggttc agtggcagtg gatcaggcac agattttaca 600

ctgaaaatca gcagagtgga ggctgaggat gttggggttt attactgcat gcaagctcta 660

caaactccgt ggacgttcgg ccaggggacc aagctggaga tcaaa 705

<210> 374

<211> 681

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 374

gaggtgcagc tggtgcagtc tggaggaggc ttgatccagc ctggggggtc cctgagactc 60

tcctgtgcag cctctgggtt caccgtcagt aggaactaca tgagctgggt ccgccaggct 120

ccagggaagg gactggagtg ggtctcagtt atttatagcg gtggtagcac atactacgca 180

gactccgtga agggccgatt caccatctcc agagacaatt ccaagaacac gctgtatctt 240

caaatgaaca gcctgagagc cgaggacacg gccgtgtatt actgtgcgag agatctggtg 300

gtttacggta tggacgtctg gggccaaggg accacggtca ccgtctcgag tgaaattgtg 360

ttgacacagt ctccaggcac cctgtctttg tctccagggg aaagagccac cctctcctgc 420

agggccagtc agagtgttag cagcagctac ttagcctggt accagcagaa acctggccag 480

gctcccaggc tcctcatcta tggtgcatcc agcagggcca ctggcatccc agacaggttc 540

agtggcagtg ggtctgggac agacttcact ctcaccatca gcagactgga gcctgaagat 600

tttgcagtgt attactgtca gcagtatggt agctcaccac gaatgtacac ttttggccaa 660

gggaccaagg tggaaatcaa a 681

<210> 375

<211> 672

<212> DNA

<213> VH_DNA_VL_DNA (Artificial Sequence)

<400> 375