KR20230163144A - Antibody binding to c-terminal of igsf1 and use thereof - Google Patents

Abstract

The present invention relates to an antibody that specifically binds to the C-terminus of IGSF1 and a pharmaceutical composition for preventing or treating cancer comprising the same as an active ingredient, and an antibody that specifically binds to the C-terminus of IGSF1 according to the present invention. The IGSF1 antibody was confirmed to have high binding specificity and binding affinity for IGSF1. In addition, it was confirmed that the anti-IGSF1 antibody promotes the death of cancer cells overexpressing IGSF1, activates surrounding immune cells, and effectively inhibits the growth of tumor tissue. Therefore, the anti-IGSF1 antibody can effectively treat cancer expressing IGSF1 and is therefore likely to be used as an anticancer agent for various cancers.

Description

Antibody binding to the C-terminus of IGSF1 and use thereof {ANTIBODY BINDING TO C-TERMINAL OF IGSF1 AND USE THEREOF}

The present invention relates to an antibody that specifically binds to the C-terminus of IGSF1 and a pharmaceutical composition for preventing or treating cancer containing the same as an active ingredient.

Cancer is a major disease that ranks first in mortality in modern society, and despite much research, there is no groundbreaking treatment to date. Worldwide, more than 100 million cancer patients occur every year, and the World Health Organization (WHO) considers cancer to be one of the main causes of death.

In the treatment of cancer, chemical treatment methods such as anticancer drugs are effective to some extent, but much research is required due to the various pathogenesis of cancer and resistance to anticancer drugs. Although cancer treatment rates have improved in recent decades due to the development of diagnostic and treatment technologies, the 5-year survival rate for many advanced cancers remains at 5 to 50%. In addition, for some cancers, survival rates have not changed significantly over the past 20 years despite various research and treatments.

As such, cancer cannot be easily treated with conventional cancer treatment regimens and recurrence and metastasis to other areas frequently occur, so a more fundamental treatment method is required. Accordingly, interest is increasing in developing substances to treat cancer by targeting biomarkers that characterize cancer malignancy, metastasis, and recurrence.

Meanwhile, Republic of Korea Patent Publication No. 10-2016-0014564 discloses that the IGSF1 (immunoglobulin superfamily member 1) gene can be used as a biomarker for predicting susceptibility to MET (mesenchymal-epithelial transition factor) inhibitors. The above document discloses that an anticancer drug with high therapeutic effect can be selected by determining the sensitivity of each patient using the biomarker before treating the cancer patient. However, there has been no disclosure that IGSF1-specific antibodies can be used as anticancer agents.

Republic of Korea Patent Publication No. 10-2016-0014564

As a result of research to develop an anticancer agent to effectively treat cancer in which IGSF1 is overexpressed, the present inventors produced an antibody that specifically binds to the C-terminus of IGSF1, and the antibody has cancer cell death, tumor growth inhibition effects, and The present invention was completed after confirming that the immune cell activation effect was excellent.

In order to achieve the above object, one aspect of the present invention provides an anti-IGSF1 antibody or fragment thereof that specifically binds to the C-terminus of IGSF1.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 3, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 5, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 7; and a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 11, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 13, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 15. Antibodies or fragments thereof are provided.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 21, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 23, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 25; and a light chain variable region comprising light chain CDR1 of SEQ ID NO: 29, light chain CDR2 of SEQ ID NO: 31, and light chain CR3 of SEQ ID NO: 33.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 39, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 41, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 43; and a light chain variable region comprising light chain CDR1 of SEQ ID NO: 47, light chain CDR2 of SEQ ID NO: 49, and light chain CR3 of SEQ ID NO: 51.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 57, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 59, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 61; and a light chain variable region comprising light chain CDR1 of SEQ ID NO: 65, light chain CDR2 of SEQ ID NO: 67, and light chain CR3 of SEQ ID NO: 69.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 75, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 77, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 79; and a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 83, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 85, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 87. Antibodies or fragments thereof are provided.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 93, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 95, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 97; and a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 101, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 103, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 105. Antibodies or fragments thereof are provided.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 111, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 113, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 115; and a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 119, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 121, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 123. Antibodies or fragments thereof are provided.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 129, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 131, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 133; and a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 137, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 139, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 141. Antibodies or fragments thereof are provided.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 147, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 149, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 151; and a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 155, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 157, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 159. Antibodies or fragments thereof are provided.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 165, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 167, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 169; and a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 173, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 175, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 177. Antibodies or fragments thereof are provided.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 183, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 185, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 187; and a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 191, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 193, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 195. Antibodies or fragments thereof are provided.

Another aspect of the present invention is a heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 219, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 221, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 223; and a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 227, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 229, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 231. Antibodies or fragments thereof are provided.

Another aspect of the present invention provides a pharmaceutical composition for preventing or treating cancer comprising the antibody or fragment thereof.

The anti-IGSF1 antibody that specifically binds to the C-terminus of IGSF1 according to the present invention was confirmed to have high binding specificity and binding affinity for IGSF1. In addition, the anti-IGSF1 antibody was confirmed to have the effect of promoting the death of cancer cells overexpressing IGSF1, activating immune cells, and effectively inhibiting the growth of tumor tissue. Therefore, the anti-IGSF1 antibody will be useful as a treatment for various cancers expressing IGSF1.

Figure 1A shows anti-IGSF1 antibodies, WM-A1-2608, WM-A1-2613, WM-A1-3102, WM-A1-3104, WM-A1-3105, WM-A1-, which bind to the C-terminus of IGSF1. This is the result of analyzing the binding affinity of 3106, WM-A1-3128, WM-A1-3132, and WM-A1-3133 to the human embryonic kidney cell lines HEK293 mock and HEK293 IGSF1.
Figure 1b shows anti-IGSF1 antibodies WM-A1-2608, WM-A1-2613, WM-A1-3102, WM-A1-3104, WM-A1-3105, WM-A1- that bind to the C-terminus of IGSF1. This is the result of analyzing the binding affinity of 3106, WM-A1-3128, WM-A1-3132, and WM-A1-3133 to human lung cancer cell lines NCI-H292 mock and NCI-H292 IGSF1.
Figure 2A shows anti-IGSF1 antibodies WM-A1-2608, WM-A1-2613, WM-A1-3102, WM-A1-3104, WM-A1-3105, WM-A1- that bind to the C-terminus of IGSF1. The immuno-anticancer efficacy of 3106, WM-A1-3128, WM-A1-3132, and WM-A1-3133 was confirmed by the T cell proliferation rate in lung cancer cell and T cell co-culture.
Figure 2b shows the immuno-anticancer efficacy of WM-A1-2608, WM-A1-2613, WM-A1-3102, and WM-A1-3104, which are anti-IGSF1 antibodies that bind to the C-terminus of IGSF1, on lung cancer cells and T cells. This result was confirmed by the production rate of the cytokine IL-2 in culture.
Figure 2c shows the immuno-anticancer efficacy of WM-A1-2608, WM-A1-2613, WM-A1-3102, and WM-A1-3104, which are anti-IGSF1 antibodies that bind to the C-terminus of IGSF1, on lung cancer cells and T cells. This result was confirmed by the production rate of cytokine TNF-α in culture.
Figure 3a shows WM-A1-2608, WM-A1-3102, WM-A1-3104, and WM-A1-3105, which are anti-IGSF1 antibodies that bind to the C-terminus of IGSF1, respectively, administered to a syngeneic mouse model of colon cancer. This is the result of observing changes in tumor size.
Figure 3b shows the results of observing changes in tumor size after administering WM-A1-2613, an anti-IGSF1 antibody that binds to the C-terminus of IGSF1, to a humanized mouse model of lung cancer.

Anti-IGSF1 antibody that specifically binds to the C-terminus of IGSF1

One aspect of the present invention provides an anti-IGSF1 antibody that specifically binds to the C-terminus of IGSF1.

As used herein, the term “Immunoglobulin superfamily member 1 (IGSF1)” is a plasma membrane glycoprotein encoded by the IGSF1 gene found on the X chromosome of humans and other mammalian species. Although the function of IGSF1 in normal cells is not well known, IGSF1 mutations are known to cause diseases such as IGSF1 deficiency syndrome or central hypothyroidism.

In the present invention, the IGSF1 may be included without limitation as long as it is mammalian IGSF1, but preferably refers to human IGSF1. Additionally, in the present invention, the IGSF1 protein may include both native or mutant IGSF1 proteins, but is not limited thereto. The native IGSF1 protein generally refers to a polypeptide containing the amino acid sequence of the native IGSF1 protein, and the amino acid sequence of the native IGSF1 protein generally refers to the amino acid sequence found in naturally occurring IGSF1. Information about IGSF1 can be obtained from known databases such as GenBank of the National Institutes of Health, and may have, for example, the amino acid sequence of Genebank accession number NP_001164433.1 or the amino acid sequence of SEQ ID NO: 235, but is not limited thereto.

As used herein, the term “C-terminus (C-terminal end) of IGSF1” refers to the carboxyl terminus of the amino acid chain of IGSF1, and is also referred to as “C-terminal domain of IGSF1.” The C-terminal domain of IGSF1 may include an extracellular domain consisting of seven Ig loops, a transmembrane domain, and a cytoplasmic tail domain.

As used herein, the term “anti-IGSF1 antibody” refers to an antibody capable of binding to IGSF1, and may be used interchangeably with “IGSF1-specific antibody” herein. In particular, anti-IGSF1 antibodies can specifically bind to the C-terminus of IGSF1. The form of the antibody may include both whole antibodies and antibody fragments.

As used herein, the term “antibody” refers to an immunoglobulin (Ig) molecule that reacts immunologically with a specific antigen, and refers to a protein molecule that acts as a receptor that specifically recognizes the antigen. It is a concept that encompasses both antibodies, whole antibodies, and antibody fragments.

Specifically, the antibody or fragment thereof may be a monoclonal antibody, polyclonal antibody, single domain antibody, single chain antibody, multispecific antibody, human antibody, or humanized antibody. (humanized) antibody, chimeric antibody, intrabody, Fv, scFv, Fv linked by disulfide bond (di-scFv), Fab fragment, F(ab') ₂ fragment and any of the above epitopes (epitope) may include a binding fragment, but is not limited thereto.

The heavy and light chains of immunoglobulins may each include a constant region and a variable region.

As used herein, the term "heavy chain" refers to a full-length heavy chain and fragments thereof comprising a variable region (VH) and three constant regions, CH1, CH2, and CH3, sufficient to confer specificity for an antigen. It is meant to include all.

As used herein, the term "light chain" is meant to include both full-length light chains and fragments thereof comprising variable regions (VL) and constant regions (CL) sufficient to confer specificity for an antigen. .

As used herein, the term “complementarity determining region (CDR)” refers to the complementarity determining region that is part of the heavy chain variable region (VH) and light chain variable region (VL) of an antibody.

The light and heavy chain variable regions of the immunoglobulin include three hypervariable regions called complementarity determining regions (CDRs) and four framework regions (FRs). The CDR mainly functions to bind to the epitope of the antigen. The CDRs of each chain are typically called CDR1, CDR2, and CDR3 sequentially starting from the N-terminus, and are identified by the chain on which the specific CDR is located.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 3, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 5, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 7. heavy chain variable region; and a light chain variable region including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 11, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 13, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 15. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 1; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 9. In this specification, the antibody may be referred to as WM-A1-2608.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with the amino acid sequence of SEQ ID NO: 5 %, about 90%, about 91%, about 92%, about 93%, about 94%, about 95% with the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 7 with about 98% or about 99% identity or 100% identity; A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 11. % or about 99% identity or 100% identity to the light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 13, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% with the amino acid sequence of SEQ ID NO: 15 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 9. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 21, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 23, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 25. heavy chain variable region; and a light chain variable region comprising light chain CDR1 of SEQ ID NO: 29, light chain CDR2 of SEQ ID NO: 31, and light chain CR3 of SEQ ID NO: 33. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 19; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 27. In this specification, the antibody may be referred to as WM-A1-2613.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with amino acid sequence of SEQ ID NO:23 %, about 98% or about 99% identity or about 100% identity to the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 25, and about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 29. % or about 99% identity or 100% identity to the light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 31, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% to the amino acid sequence of SEQ ID NO:33 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 27. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 39, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 41, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 43. heavy chain variable region; and a light chain variable region comprising light chain CDR1 of SEQ ID NO: 47, light chain CDR2 of SEQ ID NO: 49, and light chain CR3 of SEQ ID NO: 51. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 37; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 45. In this specification, the antibody may be referred to as WM-A1-3102.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with the amino acid sequence of SEQ ID NO: 41 %, about 98% or about 99% identity or about 100% identity with the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 43 and about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 47. % or about 99% identity or 100% identity to the light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 49, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% to the amino acid sequence of SEQ ID NO:51 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 45. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 57, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 59, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 61. heavy chain variable region; and a light chain variable region comprising light chain CDR1 of SEQ ID NO: 65, light chain CDR2 of SEQ ID NO: 67, and light chain CR3 of SEQ ID NO: 69. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 55; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 63. In this specification, the antibody may be referred to as WM-A1-3104.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with the amino acid sequence of SEQ ID NO:59 %, about 98%, or about 99% identity, or about 90%, about 91%, about 92%, about 93%, about 94%, about 95% with the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 61, A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 65. % or about 99% identity or 100% identity, light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 67, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% to the amino acid sequence of SEQ ID NO:69 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 63. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 75, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 77, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 79. heavy chain variable region; and a light chain variable region including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 83, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 85, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 87. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 73; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 81. In this specification, the antibody may be referred to as WM-A1-3105.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97 with the amino acid sequence of SEQ ID NO:77 %, about 90%, about 91%, about 92%, about 93%, about 94%, about 95% with the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 79 with about 98% or about 99% identity or 100% identity; A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 83. % or about 99% identity or 100% identity, light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 85, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% with the amino acid sequence of SEQ ID NO:87 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 81. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 93, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 95, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 97. heavy chain variable region; and a light chain variable region including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 101, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 103, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 105. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 91; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 99. In this specification, the antibody may be referred to as WM-A1-3106.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with the amino acid sequence of SEQ ID NO: 95 %, about 98% or about 99% identity or about 100% identity with the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 97 and about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 101. % or about 99% identity or 100% identity, light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 103, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% with the amino acid sequence of SEQ ID NO: 105 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 99. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 111, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 113, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 115. heavy chain variable region; and a light chain variable region including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 119, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 121, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 123. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 109; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 117. In this specification, the antibody may be referred to as WM-A1-3114.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with the amino acid sequence of SEQ ID NO: 113 %, about 98% or about 99% identity or about 100% identity to the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 115, and about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 119. % or about 99% identity or 100% identity, light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 121, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% to the amino acid sequence of SEQ ID NO: 123 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 117. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 129, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 131, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 133. heavy chain variable region; and a light chain variable region including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 137, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 139, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 141. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 127; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 135. In this specification, the antibody may be referred to as WM-A1-3128.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with the amino acid sequence of SEQ ID NO: 131 %, about 98% or about 99% identity or about 100% identity to the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 133 and about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 137. % or about 99% identity or 100% identity, light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 139, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% to the amino acid sequence of SEQ ID NO: 141 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 135. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 147, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 149, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 151. heavy chain variable region; and a light chain variable region including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 155, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 157, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 159. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 145; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 153. In this specification, the antibody may be referred to as WM-A1-3132.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with the amino acid sequence of SEQ ID NO: 149 %, about 98% or about 99% identity or about 100% identity to the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 151 and about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 155. % or about 99% identity or 100% identity, light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 157, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% to the amino acid sequence of SEQ ID NO: 159 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 153. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 165, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 167, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 169. heavy chain variable region; and a light chain variable region including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 173, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 175, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 177. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 163; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 171. In this specification, the antibody may be referred to as WM-A1-3133.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with the amino acid sequence of SEQ ID NO: 167 %, about 98% or about 99% identity or about 100% identity to the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 169 and about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 173. % or about 99% identity or 100% identity, light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 175, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% to the amino acid sequence of SEQ ID NO: 177 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 171. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 183, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 185, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 187. heavy chain variable region; and a light chain variable region including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 191, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 193, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 195. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 181; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 189. In this specification, the antibody may be referred to as WM-A1-3140.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with the amino acid sequence of SEQ ID NO: 185 %, about 98% or about 99% identity or about 100% identity to the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 187 and about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 191. % or about 99% identity or 100% identity, light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 193, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% to the amino acid sequence of SEQ ID NO: 195 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 189. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 201, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 203, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 205. heavy chain variable region; and a light chain variable region including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 209, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 211, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 213. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 199; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 207. In this specification, the antibody may be referred to as WM-A1-3389.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with the amino acid sequence of SEQ ID NO: 203 %, about 98% or about 99% identity or about 100% identity to the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 205 and about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 209. % or about 99% identity or 100% identity, light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 211, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% to the amino acid sequence of SEQ ID NO: 213 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 207. % or about 99% identity or 100% identity.

The IGSF1-specific antibody and fragment thereof of the present invention include a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 219, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 221, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 223. heavy chain variable region; and a light chain variable region including a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 227, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 219, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 231. At this time, the heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 217; The light chain variable region may consist of the amino acid sequence of SEQ ID NO: 225. In this specification, the antibody may be referred to as WM-A1-3399.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or Heavy chain CDR1 with about 99% identity or 100% identity, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97% with the amino acid sequence of SEQ ID NO: 221 %, about 98% or about 99% identity or about 100% identity to the heavy chain CDR2 and the amino acid sequence of SEQ ID NO: 223 and about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, A heavy chain CDR3 having about 96%, about 97%, about 98% or about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 227. % or about 99% identity or 100% identity, light chain CDR1, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96% with the amino acid sequence of SEQ ID NO: 229, Light chain CDR2 having about 97%, about 98% or about 99% identity or 100% identity and about 90%, about 91%, about 92%, about 93%, about 94%, about 95% to the amino acid sequence of SEQ ID NO:231 %, about 96%, about 97%, about 98% or about 99% identity or 100% identity.

The heavy chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% or It may comprise or consist of an amino acid sequence having about 99% identity or 100% identity. In addition, the light chain variable region of the antibody is about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98% of the amino acid sequence of SEQ ID NO: 225. % or about 99% identity or 100% identity.

Immunoglobulin heavy chain constant regions (CH) exhibit different amino acid compositions and sequences and therefore possess different types of antigenicity. Therefore, immunoglobulins can be divided into five categories and referred to as immunoglobulin isotypes, namely IgM, IgD, IgG, IgA and IgE. The corresponding heavy chains are μ chain, δ chain, γ chain, α chain and ε chain, respectively. Additionally, depending on the amino acid composition of the hinge region and the number and position of heavy chain disulfide bonds, the same type of Ig can be classified into different subtypes. For example, IgG can be classified as IgG1, IgG2, IgG3, and IgG4. Light chains can be classified as κ or λ chains depending on their different constant regions. Each of the five types of IgG can have either a κ or λ chain.

When the IGSF1-specific antibody of the present invention includes a constant region, it may include a constant region derived from IgG, IgA, IgD, IgE, IgM, or a partial hybrid thereof.

As used herein, the term “hybrid” means that within a single chain immunoglobulin heavy chain constant region there are sequences corresponding to immunoglobulin heavy chain constant regions of two or more different origins. For example, a mixture of domains consisting of 1 to 4 domains selected from the group consisting of CH1, CH2, and CH3 of IgG, IgA, IgD, IgE, and IgM is possible.

Additionally, when the IGSF1-specific antibody includes a light chain constant region (LC), the light chain constant region may be derived from a κ or λ light chain.

Polynucleotide encoding anti-IGSF1 antibody

Another aspect of the present invention provides a polynucleotide encoding an antibody specific for IGSF1 or a fragment thereof. The anti-IGSF1 antibody and fragments thereof are as described above.

If the polynucleotide encodes the same polypeptide, one or more bases may be mutated by substitution, deletion, insertion, or a combination thereof. When preparing a polynucleotide sequence by chemical synthesis, synthesis methods well known in the art, for example, methods described in the literature (Engels and Uhlmann, Angew Chem IntEd Engl., 37:73-127, 1988), can be used. and triester, phosphite, phosphoramidite and H-phosphate methods, PCR and other autoprimer methods, and oligonucleotide synthesis methods on solid supports.

In the present invention, the polynucleotide is SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: No. 107, SEQ ID No. 108, Seq. No. 125, Seq. , may consist of the base sequence of SEQ ID NO: 216, SEQ ID NO: 233, or SEQ ID NO: 234. The polynucleotide is SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 215, SEQ ID NO: 216, Each base sequence of SEQ ID NO: 233 or SEQ ID NO: 234 and at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about It may include or consist of base sequences having 99% or at least about 100% identity.

The polynucleotide may additionally include a signal sequence or leader sequence.

As used herein, the term “signal sequence” refers to a nucleic acid encoding a signal peptide that directs secretion of a target protein. The signal peptide is cleaved after translation in the host cell. Specifically, the signal sequence of the present invention is a nucleotide encoding an amino acid sequence that initiates the movement of a protein across the ER (endoplasmic reticulum) membrane.

Signal sequences are well characterized in the art and typically contain 16 to 30 amino acid residues, but may contain more or fewer amino acid residues. A typical signal peptide consists of three regions: a basic N-terminal region, a central hydrophobic region, and a more polar C-terminal region. The central hydrophobic region contains 4 to 12 hydrophobic residues that anchor the signal sequence throughout the membrane lipid bilayer while the immature polypeptide moves. After initiation, the signal sequence is cleaved within the lumen of the ER by cellular enzymes commonly known as signal peptidases. At this time, the signal sequence may be a tissue plasminogen activation (tPa), a signal sequence of herpes simplex virus glycoprotein D (HSV gDs), an IgG signal sequence, or a secretion signal sequence of growth hormone. Preferably, a secretion signal sequence used in higher eukaryotic cells, including mammals, can be used.

Signal sequences useful in the present invention include antibody light chain signal sequences, such as antibody 14.18 (Gillies et al., J. Immunol. Meth 1989. 125:191-202), and antibody heavy chain signal sequences, such as MOPC141 antibody heavy chain signal. sequence (Sakano et al., Nature, 1980. 286: 676-683) and other signal sequences known in the art (see, e.g., Watson et al., Nucleic Acid Research, 1984. 12:5145-5164). You can.

As used herein, the term “leader sequence” refers to a region of messenger RNA (mRNA) that exists upstream from the start codon and is not translated into protein.

Expression vector containing polynucleotide

Another aspect of the present invention provides a vector containing a polynucleotide encoding the IGSF1-specific antibody or fragment thereof. The IGSF1-specific antibody and fragment thereof are as described above.

The vector may be two vectors each containing polynucleotides encoding the heavy chain and the light chain, or a bicistronic expression vector containing both the polynucleotides.

As used herein, the term “vector” can be introduced into a host cell and recombined and inserted into the host cell genome. Alternatively, the vector is understood as a nucleic acid vehicle containing a nucleotide sequence capable of spontaneous replication as an episome. The vectors include linear nucleic acids, plasmids, phagemids, cosmids, RNA vectors, viral vectors, mini chromosomes and analogs thereof. Examples of viral vectors include, but are not limited to, retroviruses, adenoviruses, and adeno-related viruses.

Specifically, the vector may be plasmid DNA, phage DNA, etc., commercially developed plasmids (pUC18, pBAD, pIDTSAMRT-AMP, etc.), E. coli-derived plasmids (pYG601BR322, pBR325, pUC118, pUC119, etc.), Bacillus subtilis. plasmids (pUB110, pTP5, etc.), yeast-derived plasmids (YEp13, YEp24, YCp50, etc.), phage DNA (Charon4A, Charon21A, EMBL3, EMBL4, λgt10, λgt11, λZAP, etc.), animal virus vectors (retroviruses) ), adenovirus, vaccinia virus, etc.), insect virus vectors (baculovirus, etc.), etc. Since the expression level and modification of the protein of the vector varies depending on the host cell, it is preferable to select and use the host cell most suitable for the purpose.

Additionally, the plasmid may contain a selection marker, such as an antibiotic resistance gene, and host cells maintaining the plasmid may be cultured under selective conditions.

As used herein, the term “gene expression” or “expression” of a protein of interest is understood to mean transcription of a DNA sequence, translation of an mRNA transcript, and secretion of a fusion protein product or fragment thereof. A useful expression vector may be RcCMV (Invitrogen, Carlsbad) or variants thereof. The expression vector may include a human CMV (cytomegalovirus) promoter to promote continuous transcription of the target gene in mammalian cells and a bovine growth hormone polyadenylation signal sequence to increase the steady-state level of RNA after transcription. You can.

Transformed cells expressing anti-IGSF1 antibody

Another aspect of the present invention provides a transformed cell into which an expression vector containing a polynucleotide encoding the IGSF1-specific antibody or fragment thereof has been introduced. The IGSF1-specific antibody and fragment thereof are as described above.

As used herein, the term “transformed cell” refers to prokaryotic and eukaryotic cells into which a recombinant expression vector can be introduced. The transformed cells can be produced by introducing a vector into a host cell and transforming it. Additionally, the polynucleotide contained in the vector can be expressed to produce an antibody or fragment thereof specific to IGSF1 of the present invention.

The transformation can be performed by various methods. There is no particular limitation thereto, as long as the antibody or fragment thereof specific to IGSF1 of the present invention can be produced. Specifically, the transformation method includes CaCl ₂ precipitation and CaCl ₂ precipitation using a reducing substance called DMSO (dimethyl sulfoxide). Hanahan method, electroporation, calcium phosphate precipitation method, protoplast fusion method, stirring method using silicon carbide fiber, agrobacteria-mediated transformation method, and transformation method using PEG, which have increased efficiency by using the Hanahan method. , dextran sulfate, lipofectamine, and drying/inhibition mediated transformation methods can be used. Additionally, the target can be delivered into cells using virus particles through infection. Additionally, vectors can be introduced into host cells by gene bombardment or the like.

Additionally, the host cell used to produce the transformed cell is not particularly limited as long as it is capable of producing the fusion protein of the present invention. Specifically, the host cell may include, but is not limited to, cells of prokaryotic, eukaryotic, mammalian, plant, insect, fungal or cellular origin. An example of the prokaryotic cell may be Escherichia coli. Additionally, yeast can be used as an example of a eukaryotic cell. In addition, the mammalian cells include CHO cells, F2N cells, COS cells, BHK cells, Bowes melanoma cells, HeLa cells, 911 cells, AT1080 cells, A549 cells, SP2/0 cells, and human lymphoblastoids. ), NSO cells, HT-1080 cells, PERC.6 cells, HEK293 cells, or HEK293T cells can be used, but are not limited to these, and any cell that can be used as a mammalian host cell known to those skilled in the art can be used.

In order to optimize the properties of the anti-IGSF1 antibody and its fragment as a therapeutic agent or for other purposes, the glycosylation-related genes of the host cell are manipulated through methods known to those skilled in the art to produce an IGSF1-specific antibody and fragment thereof. The sugar chain pattern (e.g., sialic acid, fucosylation, glycosylation) can be adjusted.

Method for producing anti-IGSF1 antibody

Another aspect of the present invention provides a method for producing the IGSF1-specific antibody or fragment thereof. The IGSF1-specific antibody and fragment thereof are as described above.

The method for producing the IGSF1-specific antibody and fragment thereof includes the steps of i) culturing the transformed cell; and ii) obtaining an anti-IGSF1 antibody or fragment thereof from the cell culture.

The method of culturing the transformed cells can be performed using methods widely known in the art. Specifically, the culture is not particularly limited as long as it can be produced by expressing the IGSF1-specific antibody and fragment thereof of the present invention. Specifically, the culture may be continuously cultured in a batch process or fed batch or repeated fed batch process.

Additionally, the step of obtaining the IGSF1-specific antibody and fragment thereof from the culture may be performed by methods known in the art. Specifically, the obtaining method is not particularly limited as long as the produced antibody specific to IGSF1 of the present invention and its fragment can be obtained. Preferably, the obtaining method includes centrifugation, filtration, extraction, spraying, drying, evaporation, precipitation, crystallization, electrophoresis, fractional dissolution (e.g. ammonium sulfate precipitation), chromatography (e.g. ion exchange, It may be a method such as affinity, hydrophobicity, and size exclusion).

Uses of anti-IGSF1 antibodies

Another aspect of the present invention provides a pharmaceutical composition for preventing or treating cancer comprising the IGSF1-specific antibody and fragment thereof as an active ingredient.

As used herein, the term “cancer” refers to the aggressive nature of cells dividing and proliferating in defiance of normal growth limits, the invasive nature of infiltrating surrounding tissues, and the ability to spread to other parts of the body. It refers to a general term for diseases caused by cells with metastatic characteristics, and is used in the same sense as malignant tumor.

The cancer may be a cancer in which IGSF1 is overexpressed. In addition, the above cancers include stomach cancer, liver cancer, lung cancer, non-small cell lung cancer, colon cancer, bladder cancer, bone cancer, blood cancer, breast cancer, melanoma, thyroid cancer, parathyroid cancer, bone marrow cancer, rectal cancer, throat cancer, larynx cancer, esophagus cancer, pancreas cancer, and tongue cancer. , it may be any one selected from the group consisting of skin cancer, sinus tumor, uterine cancer, head or neck cancer, gallbladder cancer, oral cancer, anal cancer, colon cancer, and central nervous system tumor.

In addition, “treatment of cancer” means inhibiting or preventing the growth of cancer cells or tissues, which reduces cancer growth and cancer metastasis compared to no treatment or treatment, and reduces resistance to anticancer drugs. This concept also includes making the treatment more effective. The cancer metastasis refers to the process by which tumor (cancer) cells spread to distant parts of the body, and "resistance to anticancer drugs" or "anticancer drug resistance" refers to the initial stage of treatment when treating cancer patients using anticancer drugs. This means that there is no treatment effect or that the cancer treatment effect is initially effective but the cancer treatment effect is lost during the continuous treatment process. “Prevention” refers to all actions that inhibit the occurrence of cancer or delay its onset by administering the pharmaceutical composition.

In the pharmaceutical composition for preventing or treating cancer of the present invention, the anti-IGSF1 antibody or fragment thereof may be included in any amount (effective amount) depending on the use, formulation, purpose of formulation, etc., as long as it can exhibit anti-cancer activity. Here, “effective amount” refers to the amount of an active ingredient that can induce an anticancer effect. Such effective amounts can be determined experimentally within the scope of the ordinary ability of those skilled in the art. The pharmaceutical composition of the present invention contains the antibody or fragment thereof as an active ingredient in an amount of about 0.1% to about 90% by weight, specifically about 0.5% by weight to about 75% by weight, and more specifically about 1% by weight, based on the total weight of the composition. It may contain from % to about 50% by weight.

The pharmaceutical composition of the present invention may contain a conventional, non-toxic pharmaceutically acceptable carrier that is formulated into a preparation according to a conventional method.

The pharmaceutically acceptable carrier may be any carrier that is a non-toxic material suitable for delivery to a patient. Distilled water, alcohol, fats, waxes and inert solids may be included as carriers. Pharmacologically acceptable adjuvants (buffers, dispersants) may also be included in the pharmacological composition.

As used herein, the term “pharmaceutically acceptable carrier” refers to a carrier or diluent that does not irritate living organisms and does not inhibit the biological activity and properties of the administered compound. Acceptable pharmaceutical carriers in compositions formulated as liquid solutions include those that are sterile and biocompatible, such as saline solution, sterile water, Ringer's solution, buffered saline solution, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and One or more of these ingredients can be mixed and used, and other common additives such as sweeteners, solubilizers, wetting agents, emulsifiers, isotonic agents, absorbents, antioxidants, preservatives, lubricants, fillers, buffers, and bacteriostatic agents are added as needed. can do.

The compositions of the present invention can be prepared in a variety of formulations for parenteral administration (e.g., intramuscular, intravenous, or subcutaneous injection). When the pharmaceutical composition of the present invention is prepared as a parenteral formulation, it can be formulated in the form of injections, transdermal administration, nasal inhalation, and suppositories along with a suitable carrier according to methods known in the art. Injectable preparations include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As a base for suppositories, Withepsol, Macrogol, Tween 61, cacao, laurin, glycerogeratin, etc. can be used. Meanwhile, injectables may contain conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifiers, stabilizers, preservatives, etc.

Regarding the formulation of pharmaceutical compositions, it is known in the art, and specifically, references can be made to the literature [Remington's Pharmaceutical Sciences (19th ed., 1995)]. The above documents are considered part of this specification.

The antibody or composition of the present invention can be administered to a patient in a therapeutically effective amount or a pharmaceutically effective amount.

As used herein, the term "administration" means introducing a predetermined substance into an individual by an appropriate method, and the composition may be administered through any general route as long as it can reach the target tissue. . It may be administered intraperitoneally, intravenously, intramuscularly, subcutaneously, intradermally, locally, intranasally, or rectally, but is not limited thereto.

Here, “therapeutically effective amount” or “pharmaceutically effective amount” refers to the amount of the composition effective in preventing or treating the target disease, which is sufficient to treat the disease at a reasonable benefit/risk ratio applicable to medical treatment and has no side effects. It means an amount that does not cause any damage. The level of the effective amount is determined by factors including the patient's health status, type and severity of the disease, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and excretion rate, treatment period, drugs combined or used simultaneously, and It may be determined based on other factors well known in the medical field. Specifically, the therapeutically effective amount refers to the amount of drug effective in treating cancer.

Specifically, the effective amount of the antibody in the composition of the present invention may vary depending on the patient's age, gender, and weight, and is generally about 0.1 mg to about 1,000 mg, or about 5 mg to about 200 mg per kg of body weight daily. It can be administered every other day or divided into 1 to 3 doses per day. However, since it may increase or decrease depending on the route of administration, severity of disease, gender, weight, age, etc., the scope of the present invention is not limited thereto.

The antibody of the present invention or a pharmaceutical composition containing the same may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. At this time, the other therapeutic agent may additionally include any compound or natural extract whose safety has already been verified and which is known to have anticancer activity in order to increase or reinforce anticancer activity. Taking all of the above factors into consideration, it is important to administer an amount that can achieve maximum effect with minimal or no side effects, and this can be easily determined by a person skilled in the art.

Redundant content is omitted in consideration of the complexity of the present specification, and terms not otherwise defined in this specification have meanings commonly used in the technical field to which the present invention pertains.

Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as limited by these examples.

Example 1. Preparation of anti-IGSF1 antibody binding to the C-terminus of IGSF1

Example 1.1. IGSF1 antigen protein production

From the Jurkat cell cDNA library, only the extracellular domain contained in the carboxyterminal domain of IGSF1 was amplified using PCR. An ISGF1 protein expression vector was constructed by fusing human Fc (fragment crystallizable region) and his tag to the carboxy-terminus of the IGSF1 extracellular domain using the N293F vector (Y Biologics Co., Ltd.). The human embryonic kidney cell line HEK293F was transfected with the constructed IGSF1 expression vector and then cultured for 6 days in medium supplemented with 1 nM Valporic acid (valproate). Next, the IGSF1 extracellular domain was first purified using protein A agarose, and the IGSF1 extracellular domain was second purified using Superdex 200 gel filtration chromatography. The purified IGSF1 extracellular domain was used as an antigen for antibody selection.

Example 1.2. Selection of human antibodies specific for IGSF1

After coating the IGSF1 antigen purified in Example 1.1 on an immunotube and blocking, biopanning was performed using the prepared human antibody phage library (Y Biologics Co., Ltd.) Note)) was performed. Specifically, through biopanning, phages that specifically bound to the IGSF1 antigen were eluted and amplified. The second and third biopanning were performed using the phage amplified in the first biopanning. It was confirmed that anti-IGSF1 phage antibody was enriched in the phage pool obtained through third panning.

Polyphage ELISA was performed to confirm the specificity of the positive phage antibody pool obtained through the first to third biopanning with the IGSF1 antigen. Through this, it was confirmed that among the phage pools from the first to third panning, the phage pool obtained through the third biopanning had a high binding ability to IGSF1.

Hundreds of monoclones were selected from the phage pool of the third panning, and monophage ELISA was performed to confirm whether they specifically bind to IGSF1. A number of preliminary clonal antibodies that specifically bind to IGSF1 were selected, and 99 types of phages with different base sequences were identified through DNA sequence analysis of the selected preliminary antibody clones.

Example 1.3. Confirmation of specificity of selected preliminary antibodies for IGSF1 antigen

ELISA was performed to comparatively analyze the specificity of 99 positive phage clones with different base sequences identified in Example 1.2 to other antigens, including IGSF1. As control antigens, various types of unspecific antigens such as mFc, hRAGE-Fc, CD58-Fc, and ITGA6-Fc were used, and binding of phage clones to them was confirmed. Through this, 95 types of phages that specifically bind to IGSF1 were selected. The 95 selected phage clones were converted into full IgG form, and the sequences of the heavy and light chains of the converted 95 clones were confirmed to match the sequences of the phage clones. Among 95 types of antibodies, 13 most optimized antibodies were selected, and the CDR sequence information of the selected antibodies is shown in Table 1 below.

H-CDR1 H-CDR2 H-CDR3 L-CDR1 L-CDR2 L-CDR3 WM-A1-2608 GFAFRRYE
(SEQ ID NO: 3) INSGGSVK
(SEQ ID NO: 5) ARAGNAFGTFDY
(SEQ ID NO: 7) QDISRW
(SEQ ID NO: 11) AAS
(SEQ ID NO: 13) QQPISFPLT
(SEQ ID NO: 15) WM-A1-2613 GDSVISTDW
(SEQ ID NO: 21) IHHSGST
(SEQ ID NO: 23) SRGSGGRDAFDV
(SEQ ID NO: 25) MSNIGGNY
(SEQ ID NO: 29) KTN
(SEQ ID NO: 31) ASWDIGDGPTWV
(SEQ ID NO: 33) WM-A1-3102 GGTFSSYA
(SEQ ID NO: 39) IIPVLGAT
(SEQ ID NO: 41) ARGRSWGFDY
(SEQ ID NO: 43) QSLLHSDGNTY
(SEQ ID NO: 47) TLS
(SEQ ID NO: 49) MQRIEFPYT
(SEQ ID NO: 51) WM-A1-3104 GFTFSSYA
(SEQ ID NO: 57) ISYDGSNK
(SEQ ID NO: 59) ARGSGRHYQPLDH
(SEQ ID NO: 61) QTIYRY
(SEQ ID NO: 65) AAS
(SEQ ID NO: 67) QQLKNYPLT
(SEQ ID NO: 69) WM-A1-3105 GRSTYNYA
(SEQ ID NO: 75) IIPIFGAT
(SEQ ID NO: 77) AKGSGNYYYGMDV
(SEQ ID NO: 79) QSVGTW
(SEQ ID NO: 83) AAS
(SEQ ID NO: 85) QQADSFPYT
(SEQ ID NO: 87) WM-A1-3106 GFTFGDYA
(SEQ ID NO: 93) ISGDGGTT
(SEQ ID NO: 95) ARGGRVYGMDV
(SEQ ID NO: 97) QGISVW
(SEQ ID NO: 101) GSS
(SEQ ID NO: 103) QQYKASPPT
(SEQ ID NO: 105) WM-A1-3114 GFSFDDYA
(SEQ ID NO: 111) ISWNSRTM
(SEQ ID NO: 113) ARTKGFPGHFHE
(SEQ ID NO: 115) SGSFANY
(SEQ ID NO: 119) GDNQR
(SEQ ID NO: 121) QSYDSRNRNYV
(SEQ ID NO: 123) WM-A1-3128 GFSLRTYG
(SEQ ID NO: 129) IWHDGSHT
(SEQ ID NO: 131) ARGGSYSRYSDAFDI
(SEQ ID NO: 133) QSVSSSY
(SEQ ID NO: 137) DAS
(SEQ ID NO: 139) QQRSNWPLT
(SEQ ID NO: 141) WM-A1-3132 GYSLSELS
(SEQ ID NO: 147) GYSLSELS
(SEQ ID NO: 149) ARDLPELRGVLAD
(SEQ ID NO: 151) SSDVGGYDY
(SEQ ID NO: 155) DAS
(SEQ ID NO: 157) SSYTRSSSTLV
(SEQ ID NO: 159) WM-A1-3133 GFSFDDYG
(SEQ ID NO: 165) ISGSGGST
(SEQ ID NO: 167) ARGGRVYGMDV
(SEQ ID NO: 169) HDIRRW
(SEQ ID NO: 173) AAA
(SEQ ID NO: 175) QKYDSVPFT
(SEQ ID NO: 177) WM-A1-3140 GFNFHNYA
(SEQ ID NO: 183) ISWNSGSI
(SEQ ID NO: 185) AGLKGMNWFDP
(SEQ ID NO: 187) SGSFANY
(SEQ ID NO: 191) GDNQR
(SEQ ID NO: 193) QSYDSNNHWV
(SEQ ID NO: 195) WM-A1-3389 GGTFSTYA
(SEQ ID NO: 201) IIPFVGTV
(SEQ ID NO: 203) VRDGRSYFDS
(SEQ ID NO: 205) TSNIGSNL
(SEQ ID NO: 209) DNH
(SEQ ID NO: 211) VAWDDSLNGYV
(SEQ ID NO: 213) WM-A1-3399 GFTFNKYG
(SEQ ID NO: 219) ISPSGSLQ
(SEQ ID NO: 221) AAGLIGGATAAFDN
(SEQ ID NO: 223) SSDIGDYSF
(SEQ ID NO: 227) DVY
(SEQ ID NO: 229) SSYATDRTLV
(SEQ ID NO: 231)

Experimental Example 1. Measurement of binding affinity of anti-IGSF1 antibody

Experimental Example 1.1. Preparation of IGSF1 overexpressing human cell lines

The human lung cancer cell line NCI-H292 or the human embryonic kidney cell line HEK293E were genetically engineered to overexpress IGSF1 (HEK293 IGSF1, NCI-H292 IGSF1). As a negative control, an empty vector (pCMV6 entry, Origene PS100001) that does not contain the polynucleotide encoding IGSF1 was used (HEK293 mock, NCI-H292 mock). Specifically, an expression vector (pCMV6 entry IGSF1, OriGene Technologies, Inc, Cat No RC209621) containing a polynucleotide encoding IGSF1 was transfected into NCI-H292 and HEK293F, respectively. Subsequently, the transfected cells were selected while culturing in a medium containing G418 (neomycin). The IGSF1 expression level of the selected cells was confirmed, and the cells showing the highest IGSF1 expression were selected and used in the experiment.

Experimental Example 1.2. Determination of binding affinity to IGSF1 overexpressing human cell lines

The medium of the HEK293 mock, HEK293 IGSF1, NCI-H292 mock, and NCI-H292 IGSF1 cells prepared in Experimental Example 1.1 was removed, washed once with PBS (phosphate-buffered saline), and then washed with 1 ml of 0.05% trypsin-EDTA. The cells were separated by treatment. The separated cells were diluted with 9 ml of PBS (hereinafter referred to as FACS buffer) containing 2% FBS and 0.05% NaN ₃ and centrifuged at 800 rpm for 3 minutes to remove the supernatant. The cells were resuspended by adding FACS buffer to a concentration of 5x10 ⁵ cell/ml, then dispensed into 1 ml tubes and centrifuged at 4°C for 2 minutes to remove the supernatant.

In each cell, a control human IgG1 (IgG isotype) (Bio -2613, WM-A1-3102, WM-A1-3104, WM-A1-3105, WM-A1-3106, WM-A1-3128, WM-A1-3132, WM-A1-3133) each in FACS buffer 100 0.5 μg per μl was added and reacted on ice for 30 minutes. After the reaction was completed, 1 ml of FACS buffer was added to each tube, and then centrifuged at 4°C and 1,200 rpm for 2 minutes to remove the supernatant. After repeating this process once more, the supernatant was removed, and 0.5 μg of FITC-labeled anti-human IgG (Invitrogen, 62-8411) was added per 100 μl of FACS buffer and reacted on ice for 30 minutes.

After the reaction was completed, 1 ml of FACS buffer was added to each tube, and then centrifuged at 4°C and 1,200 rpm for 2 minutes to remove the supernatant. After repeating this process once more, the supernatant was removed and resuspended by adding 200 μl of FACS buffer. The value of FITC labeled on the cells was measured using MACS Quant10, a flow cytometer, and the measured value was analyzed using MACS Quant10 software. The binding force of the anti-IGSF1 antibody was measured based on the control group, and the results are shown in Figures 1A and 1B.

As shown in Figure 1a, the binding affinity of the anti-IGSF1 antibody binding to the IGSF1 C-terminus in HEK293 mock is very low, and in HEK293 IGSF1, the binding affinity is very high, as most antibodies bind to cells. Confirmed.

In addition, as shown in Figure 1b, the binding affinity of the anti-IGSF1 antibody that binds to the IGSF1 C-terminus in NCI-H292 mock is very low, and in NCI-H292 IGSF1, most of the antibodies bind to cells. It was confirmed that the affinity was very high.

Experimental Example 1.3. Binding affinity measurement for IGSF1 antigen

WM-A1-2608, WM-A1-2613, WM-A1-3102, WM-A1-3104, WM-A1-3105, WM, which are anti-IGSF1 antibodies that bind to the C-terminus of IGSF1 prepared in Example 1 To analyze the binding affinity of -A1-3106, WM-A1-3128, WM-A1-3132, and WM-A1-3133 to the IGSF1 antigen, ELISA was performed. Specifically, starting from 100 nM, the concentration of human IGSF1 single antigen was diluted by 1/3 until it reached 0.046 nM and sequentially added to each well, followed by WM-A1-, an anti-IGSF1 antibody that binds to the C-terminus of IGSF1. 2608, WM-A1-2613, WM-A1-3102, WM-A1-3104, WM-A1-3105, WM-A1-3106, WM-A1-3128, WM-A1-3132, WM-A1-3133 respectively. The affinity was measured. The measurement results were analyzed using GraphPad Prism 6 software, and the results are shown in Table 2.

WM-A1-2608 WM-A1-2613 WM-A1-3102 WM-A1-3104 WM-A1-3105 WM-A1-3106 WM-A1-3128 WM-A1-3132 WM-A1-3133 Kd 9.7*10 ^-11 1.0*10 ^-10 1.876*10 ^-8 2.497*10 ^-8 2.947*10 ^-8 2.079*10 ^-8 2.72*10 ^-8 17.67*10 ^-8 29.97*10 ^-8 R squared 0.9974 0.9788 0.9938 0.98 0.9834 0.9738 0.9787 0.9947 0.9551

As shown in Table 2, it was confirmed that most of the anti-IGSF1 antibodies binding to the C-terminus of IGSF1 prepared in Example 1 showed high binding affinity to the IGSF1 antigen.

Experimental Example 2. Analysis of immune anti-cancer efficacy of anti-IGSF1 antibody

Experimental Example 2.1. Confirmation of T cell activation effect

Jurkat cells (ATCC, Clone E6-1) labeled with CFSE (Invitrogen, C34554), 10% FBS, and 1% penicillin-streptomycin were added to the NCI-H292 MOCK cells and NCI-H292 IGSF1 cells prepared in Experimental Example 1.1, respectively. Co-cultured in RPMI1640 medium.

Specifically, to stimulate T cells before co-culture, human anti-CD3 antibody (BD, cat. # 555329) and human anti-CD28 (BD, cat. # 555725) were each added to PBS at a concentration of 1 μg/ml. After dilution, it was reacted with T cells for 2 hours. After stimulating T cells, lung cancer cells were distributed in a ²⁴ -well plate (Eppendorf, cat. # 0030722116) at a 1:10 ratio of ⁵ Next, control IgG (Bio WM-A1-3104, WM-A1-3105, WM-A1-3106, WM-A1-3128, WM-A1-3132, WM-A1-3133) were treated at 10 ㎍/㎖ each, and lung cancer was treated for 48 hours. Cells and T cells were co-cultured.

After the culture was completed, Jurkat cells were obtained, washed by adding 1 ml of Stain Buffer (BD, cat. # 554656), centrifuged at 1,200 rpm for 3 minutes, the supernatant was removed, and the cells were collected. Subsequently, after adding 200 ㎕ of Stain Buffer, T cell proliferation was measured using BD LSRFortessa-?? It was analyzed with a Flow Cytometer and the results are shown in Table 3 and Figure 2a below.

T cell proliferation IgG WM-A1-2608 WM-A1-2613 WM-A1-3102 WM-A1-3104 WM-A1-3105 WM-A1-3106 WM-A1-3128 WM-A1-3132 WM-A1-3133 NCI-H292 Mock Avg. 1.00 1.13 1.22 1.28 1.30 0.90 0.94 0.82 0.79 0.68 p-value 0.0079 0.2125 0.0682 0.0466 0.3310 0.5959 0.0101 0.0141 0.0000 NCI-H292IGSF1 Avg. 1.00 1.02 1.27 1.40 1.39 0.98 0.93 0.88 0.76 0.79 p-value 0.8438 0.2385 0.0393 0.0429 0.7276 0.2515 0.1723 0.0384 0.0921

As shown in Figure 2a, when the IGSF1 overexpressing lung cancer cell line was treated with the anti-IGSF1 antibody binding to the C-terminus of IGSF1 prepared in Example 1, the T cell proliferation rate was confirmed to be increased or at a similar level compared to the control group. did.

Experimental Example 2.2. Confirm the effect of cytokine production

Anti-CD3 antibody (BD Pharmingen, 555329) was diluted in PBS to a concentration of 1 μg/ml, dispensed into a 6-well plate, and coated in a carbon dioxide incubator at 37°C for 2 hours. Jurkat cells (ATCC, Clone E6-1) were centrifuged at 1,500 rpm for 10 minutes to remove the supernatant, and then resuspended by adding PBS. CFSE (carboxyfluorescein diacetate succinimidyl ester) was diluted by adding 18 μl of DMSO (dimethyl sulfoxide) to a concentration of 5 mM, and then adding PBS to a concentration of 1 mM. 1 μl of 1 mM CFSE (Invitrogen, C34554) was added per 1x10 ⁶ cells/ml of Jurkat cells, and then stained for 10 minutes in a carbon dioxide incubator at 37°C. After adding medium containing 5 times the amount of PBS (Fetal Bovine Serum) containing stained Jurkat cells, the mixture was incubated in a carbon dioxide incubator at 37°C for 5 minutes. The supernatant was removed by centrifugation at 1,500 rpm for 10 minutes, and medium was added to resuspend the stained Jurkat cells.

After washing the CD3 antibody-coated wells once with PBS, NCI-H292 Mock and NCI-H292 IGSF1 cells prepared in Experimental Example 1.1 and CFSE-labeled Jurkat cells (ATCC, Clone E6-1) were each incubated at 1:1 It was divided into 5 ratios. Next, 1 μg/ml of anti-CD28 antibody (BD Pharmingen, 555725), a control IgG (Bio A1-2608, WM-A1-2613, WM-A1-3102, WM-A1-3104) were treated at 1 μg/ml each and cultured in a carbon dioxide incubator at 37°C for 72 hours.

The supernatant of the cultured cells was placed in a 15 ml tube and stored on ice. The cells were washed once with PBS and then treated with 500 ㎕ of 0.25% trypsin-EDTA to separate the cells. The isolated cells were diluted with 2 ml of PBS containing 2% FBS and centrifuged at 1,500 rpm for 3 minutes. The resulting cell pellet was added to the supernatant stored in a 15 ml tube, resuspended, and then centrifuged at 1,500 rpm for 3 minutes. After removing the supernatant, 200 ㎕ of Fixation/Permeabilization solution (BD Bioscience, 554722) was added and reacted at 4°C for 20 minutes. Then, 1 ml of Perm/Wash buffer (BD Bioscience, 554723) diluted to 1x was added, and the supernatant was removed by centrifugation at 1,500 rpm for 3 minutes. After repeating this process once more, 200 ㎕ of Perm/Wash buffer was added and resuspended, BV421-labeled anti-IL-2 antibody and APC-labeled anti-TNF-α antibody were added, and incubated at 4°C. It was reacted for 30 minutes. After completion of the reaction, 1 ml of FACS buffer was added, and the supernatant was removed by centrifugation at 1,500 rpm for 3 minutes. After repeating this process one more time, BV421 (IL-2) and APC (TNF-α) labeled on the cells were measured using the LSRFortessa equipment, and the measured values were analyzed using FlowJo software and the results are as follows. It is shown in Tables 4 and 5 and Figures 2b and 2c.

IL-2 production IgG WM-A1-2608 WM-A1-2613 WM-A1-3102 WM-A1-3104 NCI-H292 Mock 1.00 1.16 1.68 1.16 1.11 NCI-H292 IGSF1 O/E 1.00 3.25 7.58 5.58 6.08

TNF-α production IgG WM-A1-2608 WM-A1-2613 WM-A1-3102 WM-A1-3104 NCI-H292 Mock 1.00 1.05 1.16 1.19 1.19 NCI-H292 IGSF1 O/E 1.00 1.68 1.88 1.32 1.41

As shown in Figure 2b, when the IGSF1 overexpressing lung cancer cell line was treated with the anti-IGSF1 antibody that binds to the C-terminus of IGSF1 prepared in Example 1, the production rate of IL-2 was confirmed to increase compared to the control group. .

In addition, as shown in Figure 2c, when the IGSF1 overexpressing lung cancer cell line was treated with the anti-IGSF1 antibody that binds to the C-terminus of IGSF1 prepared in Example 1, the production rate of TNF-α increased compared to the control group. Confirmed.

Experimental Example 3. Analysis of anticancer efficacy of anti-IGSF1 antibody in cancer animal model

Experimental Example 3.1. Confirmation of tumor growth inhibition effect in colon cancer model

After purchasing a 5-week-old female BALB/c mouse and acclimatizing it for a week, CT26 (5Υ10 ⁵ cells/mice), a mouse-derived colon cancer cell line, was diluted in PBS and injected subcutaneously (100 ㎕) into the right abdominal side of the mouse. A cancer syngeneic mouse model was prepared. When the tumor size reached about 100 mm ³ , negative control group, anti-IGSF1 antibody (WM-A1-2608, WM-A1-3102, WM-A1-3104) binding to the C-terminus of IGSF1 prepared in Example 1 , WM-A1-3105) were administered intraperitoneally at a dose of 20 mg/kg, respectively. Administration was carried out for 2 weeks at intervals of once every 3 days, and tumor size was measured twice a week. The change in tumor size according to the administered substance is shown in Figure 3a, and the tumor growth inhibition rate (TGI) is shown in Table 6 below.

WM-A1-2608 WM-A1-3102 WM-A1-3104 WM-A1-3105 Dose(mg/kg) 20 TGI(%) 36.2 ± 10.6 23.6 ± 4.0 47.5 ± 5.4 48.1 ± 4.2

As shown in Figure 3a, when the colon cancer mouse model was treated with the anti-IGSF1 antibody that binds to the C-terminus of IGSF1 prepared in Example 1, the size of the tumor was confirmed to be significantly reduced compared to the control group. . Through this, it was confirmed that the anti-IGSF1 antibody binding to the C-terminus of IGSF1 prepared in Example 1 had an excellent tumor growth inhibitory effect.

Experimental Example 3.2. Confirmation of tumor growth inhibition effect in lung cancer model

6-week-old female PBMC humanized mice (Gem biosciences) were purchased and acclimatized for a week, and then the IGSF1-overexpressing human lung cancer cells NCI-H292 IGSF1 (5x10 ⁶ cells/mice) prepared in Experimental Example 1.1 were added to PBS and Matrigel. It was diluted and injected subcutaneously (200 μl) into the right ventral side of the mouse. When the size of the tumor reached about 100 mm ³ , a negative control, an anti-IGSF1 antibody (WM-A1-2613) binding to the C-terminus of IGSF1 prepared in Example 1, was intraperitoneally administered at a dose of 10 mg/kg. Administration was carried out for 3 weeks at intervals of once every 3 days, and tumor size was measured twice a week. Changes in tumor size following administration of WM-A1-2613 are shown in Figure 3b, and tumor growth inhibition (TGI) is shown in Table 7 below.

WM-A1-2613 Dose(mg/kg) 10 TGI(%) 77.8 ± 4.5

As shown in Figure 3b, when the lung cancer humanized mouse model was treated with the anti-IGSF1 antibody that binds to the C-terminus of IGSF1 prepared in Example 1, the size of the tumor was confirmed to be significantly reduced compared to the control group. . Through this, it was confirmed that the anti-IGSF1 antibody binding to the C-terminus of IGSF1 prepared in Example 1 had an excellent tumor growth inhibitory effect.

<110> Wellmarker Bio Co., LTD. <120> ANTIBODY BINDING TO C-TERMINAL OF IGSF1 AND USE THEREOF <130> SPD22-037_WMB <160> 235 <170> KoPatentIn 3.0 <210> 1 <211> 119 <212> PRT <213> Artificial Sequence <220> < 223> Variable region of heavy chain of SA2608 <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 Glu Ala Ser Gly Phe Ala Phe Arg Arg Tyr 20 25 30 Glu Met Asn Trp Val Arg Gln Thr Pro Gly Lys Gly Leu Glu Trp Ile 35 40 45 Ala Tyr Ile Asn Ser Gly Gly Ser Val Lys Val Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Ala Ile Ser Arg Asn Asp Ser 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 Arg Ala Gly Asn Ala Phe Gly Thr Phe Asp Tyr Trp Gly Gln Gly 100 105 110 Thr Leu Val Thr Val Ser Ser 115 <210> 2 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> H-FR1 of SA2608 <400> 2 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 Glu Ala Ser 20 25 <210> 3 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR1 of SA2608-041D01 < 400> 3 Gly Phe Ala Phe Arg Arg Tyr Glu 1 5 <210> 4 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA2608 <400> 4 Met Asn Trp Val Arg Gln Thr Pro Gly Lys Gly Leu Glu Trp Ile Ala 1 5 10 15 Tyr <210> 5 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR2 of SA2608 <400> 5 Ile Asn Ser Gly Gly Ser Val Lys 1 5 <210> 6 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> H-FR3 of SA2608 <400> 6 Val Tyr Ala Asp Ser Val Lys Gly Arg Phe Ala Ile Ser Arg Asn Asp 1 5 10 15 Ser Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 7 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> H-CDR3 of SA2608 <400> 7 Ala Arg Ala Gly Asn Ala Phe Gly Thr Phe Asp Tyr 1 5 10 <210> 8 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-FR4 of SA2608 <400> 8 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 1 5 10 <210> 9 <211> 107 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA2608 <400> 9 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 Asp Ile Ser Arg Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Leu Met 35 40 45 Tyr Ala Ala Ser Val Leu Asp Val Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Asn Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Pro Ile Ser Phe Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys 100 105 <210> 10 <211> 26 <212> PRT <213 > Artificial Sequence <220> <223> L-FR1 of SA2608 <400> 10 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 20 25 <210> 11 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> L-CDR1 of SA2608 <400> 11 Gln Asp Ile Ser Arg Trp 1 5 <210> 12 <211> 17 <212 > PRT <213> Artificial Sequence <220> <223> L-FR2 of SA2608 <400> 12 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Arg Leu Met 1 5 10 15 Tyr <210> 13 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA2608 <400> 13 Ala Ala Ser 1 <210> 14 <211> 36 <212> PRT <213> Artificial Sequence <220> < 223> L-FR3 of SA2608 <400> 14 Val Leu Asp Val Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 1 5 10 15 Thr Asp Phe Thr Leu Thr Ile Ser Asn Leu Gln Pro Glu Asp Phe Ala 20 25 30 Thr Tyr Tyr Cys 35 <210> 15 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> L-CDR3 of SA2608 <400> 15 Gln Gln Pro Ile Ser Phe Pro Leu Thr 1 5 <210 > 16 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-FR4 of SA2608 <400> 16 Phe Gly Gly Gly Thr Lys Val Asp Ile Lys 1 5 10 <210> 17 <211> 357 <212> DNA <213> Artificial Sequence <220> <223> Variable region of heavy chain gene of SA2608 <400> 17 caggtgcagc tggtacagtc tgggggaggc ttggtacagc ctggagggtc cctgagactc 60 tcctgtgaag cctctggatt cgccttcagg cgctatgaga tga attgggt ccgccagact 120 ccagggaagg ggctggagtg gattgcatat attaatagtg gcggtagtgt caaagtctat 180 gcagactctg tgaagggccg attcgccatc tccagaaacg acagcaaaaa ctccctgtat 240 ctgcaaatga acagtctgag agccgaggac acggccgtgt attactgtgc gagagccggg 300 aatgcctttg ggacctttga ctactggggc cagggaacgc tggtcaccgt ctcctca 35 7 <210> 18 <211> 321 <212> DNA <213> Artificial Sequence <220> <223> Variable region of light chain gene of SA2608 <400> 18 gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60 atcacttgtc gggcgagtca ggatattagc aggtggttag cctggtatca gcagaaacca 120 gggaaagccc ctaagcgcct gatgtatgct gcgtccgt tt tggatgttgg ggtcccatca 180 aggttcagcg gcagtggatc tgggacagat ttcactctca ctatcagcaa cctgcagcct 240 gaggattttg ctacttacta ttgtcaacag cctatcagtt ttcctctcac tttcggcgga 300 gggaccaagg tggatatcaa a 3 21 <210> 19 <211 > 119 <212> PRT <213> Artificial Sequence <220> <223> Variable region of heavy chain of SA2613 <400> 19 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gly 1 5 10 15 Thr Leu Ser Leu Thr Cys Ala Val Ser Gly Asp Ser Val Ile Ser Thr 20 25 30 Asp Trp Trp Ser Trp Val Arg Gln Pro Pro Gly Lys Glu Leu Glu Trp 35 40 45 Ile Gly Glu Ile His His Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu 50 55 60 Glu Gly Arg Val Thr Ile Ser Val Asp Lys Ser Lys Asn Gln Phe Ser 65 70 75 80 Leu Lys Leu Thr Ser Val Thr Ala Val Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ser Arg Gly Ser Gly Gly Arg Asp Ala Phe Asp Val Trp Gly Gln Gly 100 105 110 Thr Met Ile Thr Val Ser Ser 115 <210> 20 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> H-FR1 of SA2613 < 400> 20 Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gly 1 5 10 15 Thr Leu Ser Leu Thr Cys Ala Val Ser 20 25 <210> 21 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> H-CDR1 of SA2613 <400> 21 Gly Asp Ser Val Ile Ser Thr Asp Trp 1 5 <210> 22 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA2613 <400> 22 Trp Ser Trp Val Arg Gln Pro Pro Gly Lys Glu Leu Glu Trp Ile Gly 1 5 10 15 Glu <210> 23 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> H-CDR2 of SA2613 <400> 23 Ile His His Ser Gly Ser Thr 1 5 <210> 24 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> H-FR3 of SA2613 < 400> 24 Asn Tyr Asn Pro Ser Leu Glu Gly Arg Val Thr Ile Ser Val Asp Lys 1 5 10 15 Ser Lys Asn Gln Phe Ser Leu Lys Leu Thr Ser Val Thr Ala Val Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 < 210> 25 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> H-CDR3 of SA2613 <400> 25 Ser Arg Gly Ser Gly Gly Arg Asp Ala Phe Asp Val 1 5 10 <210> 26 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-FR4 of SA2613 <400> 26 Trp Gly Gln Gly Thr Met Ile Thr Val Ser Ser 1 5 10 <210> 27 <211> 112 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA2613-045H07 <400> 27 Gln Ser Ala Leu Thr Gln Pro Pro Ser Ser Ser Gly Thr Pro Gly Gln 1 5 10 15 Lys Val Thr Ile Ser Cys Ser Gly Ser Met Ser Asn Ile Gly Gly Asn 20 25 30 Tyr Val Ser Trp Tyr Gln Gln Val Pro Gly Thr Ala Pro Lys Leu Leu 35 40 45 Ile Phe Lys Thr Asn Gln Gly Ala Ala Gly Val Pro Asp Arg Phe Val 50 55 60 Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Arg 65 70 75 80 Pro Glu Asp Glu Ala Thr Tyr Tyr Cys Ala Ser Trp Asp Asp Ile Gly 85 90 95 Asp Gly Pro Thr Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 100 105 110 <210> 28 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> L-FR1 of SA2613 <400> 28 Gln Ser Ala Leu Thr Gln Pro Pro Ser Ser Ser Gly Thr Pro Gly Gln 1 5 10 15 Lys Val Thr Ile Ser Cys Ser Gly Ser 20 25 <210> 29 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> L -CDR1 of SA2613 <400> 29 Met Ser Asn Ile Gly Gly Asn Tyr 1 5 <210> 30 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> L-FR2 of SA2613 <400> 30 Val Ser Trp Tyr Gln Gln Val Pro Gly Thr Ala Pro Lys Leu Leu Ile 1 5 10 15 Phe <210> 31 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA2613 < 400> 31 Lys Thr Asn 1 <210> 32 <211> 36 <212> PRT <213> Artificial Sequence <220> <223> L-FR3 of SA2613 <400> 32 Gln Gly Ala Ala Gly Val Pro Asp Arg Phe Val Gly Ser Lys Ser Gly 1 5 10 15 Thr Ser Ala Ser Leu Val Ile Ser Gly Leu Arg Pro Glu Asp Glu Ala 20 25 30 Thr Tyr Tyr Cys 35 <210> 33 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> L-CDR3 of SA2613 <400> 33 Ala Ser Trp Asp Asp Ile Gly Asp Gly Pro Thr Trp Val 1 5 10 <210> 34 <211> 10 <212> PRT <213> Artificial Sequence <220 > <223> L-FR4 of SA2613 <400> 34 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 1 5 10 <210> 35 <211> 357 <212> DNA <213> Artificial Sequence <220> <223> Variable region of heavy chain gene of SA2613 <400> 35 caggtgcagc tgcaggagtc gggcccagga ctggtgaagc cttcggggac cctgtccctc 60 acgtgcgctg tttctggtga ctcagtcatc agtactgact ggtggagttg ggtccgccag 120 cccccaggga aggaactgg a gtggataggg gaaatccatc atagtggaag caccaactac 180 aacccgtccc tcgagggtcg agtcaccata tcagtagaca agtccaagaa ccagttctcc 240 ctgaagttga cctctgtgac cgccgtggac acggccgtgt attactgttc ccgcggtagt 300 ggt ggtcgtg acgcttttga tgtctggggc caaggaacaa tgatcaccgt ctcctca 357 <210> 36 <211> 336 <212> DNA <213> Artificial Sequence <220> <223> Variable region of light chain gene of SA2613 <400> 36 cagtctgccc tgactcagcc tccctcctcg tctgggaccc ccggacagaa ggtcacaatc 6 0 tcttgttctg gaagcatgtc caacatcggg ggcaactacg tttcttggta ccagcaggtc 120 ccaggaacgg cccccaaact cctcatcttc aagaccaatc agggggccgc aggggtccct 180 gaccgattcg tcggctccaa gtctggaacc tcagcctccc tggtcatcag tgggctccgg 240 cccgaagatg aggcgactta ttaattgtgcg tcctgggatg acat tgggga tggcccaact 300 tgggtgttcg gcggagggac caagctgacc gtccta 336 <210> 37 <211> 117 <212> PRT <213> Artificial Sequence <220> <223 > Variable region of heavy chain of SA3102 <400> 37 Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Ser Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Gly Ile Ile Pro Val Leu Gly Ala Thr Asn Tyr Ala Gln Arg Phe 50 55 60 Gln Gly Arg Val Thr Met Thr Ala Asp Glu Ser Thr Thr Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Gly Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Gly Arg Ser Trp Gly Phe Asp Tyr Trp Gly His Gly Thr Leu 100 105 110 Ile Thr Val Ser Ser 115 <210> 38 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> H-FR1 of SA3102 <400> 38 Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser 20 25 <210> 39 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR1 of SA3102 <400> 39 Gly Gly Thr Phe Ser Ser Tyr Ala 1 5 <210> 40 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA3102 <400> 40 Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly 1 5 10 15 Gly <210> 41 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR2 of SA3102 <400> 41 Ile Ile Pro Val Leu Gly Ala Thr 1 5 <210> 42 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> H-FR3 of SA3102 <400> 42 Asn Tyr Ala Gln Arg Phe Gln Gly Arg Val Thr Met Thr Ala Asp Glu 1 5 10 15 Ser Thr Thr Thr Ala Tyr Met Glu Leu Ser Gly Leu Arg Ser Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 43 <211> 10 <212> PRT <213> Artificial Sequence <220 > <223> H-CDR3 of SA3102 <400> 43 Ala Arg Gly Arg Ser Trp Gly Phe Asp Tyr 1 5 10 <210> 44 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H -FR4 of SA3102 <400> 44 Trp Gly His Gly Thr Leu Ile Thr Val Ser Ser 1 5 10 <210> 45 <211> 112 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA3102 <400> 45 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu His Ser 20 25 30 Asp Gly Asn Thr Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser 35 40 45 Pro Gln Leu Leu Ile Tyr Thr Leu Ser His 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 Asp Asp Val Gly Leu Tyr Tyr Cys Met Gln Arg 85 90 95 Ile Glu Phe Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 100 105 110 <210> 46 <211> 26 < 212> PRT <213> Artificial Sequence <220> <223> L-FR1 of SA3102 <400> 46 Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Thr Pro Gly 1 5 10 15 Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser 20 25 <210> 47 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> L-CDR1 of SA3102 <400> 47 Gln Ser Leu Leu His Ser Asp Gly Asn Thr Tyr 1 5 10 <210> 48 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> L-FR2 of SA3102 <400> 48 Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile 1 5 10 15 Tyr <210> 49 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA3102 <400> 49 Thr Leu Ser 1 <210> 50 <211> 36 <212 > PRT <213> Artificial Sequence <220> <223> L-FR3 of SA3102 <400> 50 His Arg Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly 1 5 10 15 Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Asp Asp Val Gly 20 25 30 Leu Tyr Tyr Cys 35 <210> 51 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> L-CDR3 of SA3102 <400> 51 Met Gln Arg Ile Glu Phe Pro Tyr Thr 1 5 <210> 52 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-FR4 of SA3102 <400> 52 Phe Gly Gln Gly Thr Lys Val Glu Ile Lys 1 5 10 <210> 53 <211> 351 <212> DNA <213> Artificial Sequence <220> <223> Variable region of heavy chain gene of SA3102 <400> 53 cagatgcagc tggtacagtc tggagctgag gtgaagaagc ctgggtcctc ggtgaaggtc 60 tcct gcaagg cttctggagg caccttcagc agctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaggg atcatccctg tcttgggtgc cacaaactac 180 gcacagaggt tccagggcag agtcaccatg accgcggacg aatccacgac cacagcctac 240 atggagctga gcggcctgag atctgaggac acggcc gtgt attactgtgc gagaggggagg 300 tcgtgggggt ttgactactg gggccacgga accctgatca ccgtctcctc a 351 <210> 54 <211> 336 <212> DNA <213> Artificial Sequence <220 > <223> Variable region of light chain gene of SA3102 <400> 54 gatattgtga tgacccagac tccactctcc ctgcccgtca cccctggaca gccggcctcc 60 atctcctgca agtctagtca gagcctcctc catagtgatg gaaacaccta tctggactgg 120 tacctgcaga agccagggca gtct ccacaa ctcctcatct atacactttc tcatcgggcc 180 tctggagtcc cagacaggtt cagtggcagt gggtcaggca ctgatttcac actgaaaatc 240 agcagggtgg aggctgacga tgttggactt tattactgca tgcaacgtat agagtttcct 300 tacacttttg gccaagggac caaggtggag atcaaa 336 <210> 55 <211> 120 <212> PRT <213> Artificial Sequence <220> <223> Variable region of heavy chain of SA3104 <400> 55 Gln Val Gln Leu Val Gln 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 Arg Gly Ser Gly Arg His Tyr Gln Pro Leu Asp His Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 56 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> H-FR1 of SA3104 <400> 56 Gln Val Gln Leu Val Gln Ser Gly Gly Gly Val Val Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25 <210 > 57 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR1 of SA3104 <400> 57 Gly Phe Thr Phe Ser Ser Tyr Ala 1 5 <210> 58 <211> 17 <212 > PRT <213> Artificial Sequence <220> <223> H-FR2 of SA3104 <400> 58 Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala 1 5 10 15 Val <210> 59 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR2 of SA3104 <400> 59 Ile Ser Tyr Asp Gly Ser Asn Lys 1 5 <210> 60 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> H- FR3 of SA3104 <400> 60 Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn 1 5 10 15 Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 61 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> H-CDR3 of SA3104 <400> 61 Ala Arg Gly Ser Gly Arg His Tyr Gln Pro Leu Asp His 1 5 10 <210> 62 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-FR4 of SA3104 <400> 62 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 1 5 10 <210> 63 <211> 107 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA3104 <400> 63 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 Thr Ile Tyr Arg Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Glu Pro Gly Ala Pro Pro Lys Leu Leu Ile 35 40 45 Ser 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 Lys Asn Tyr Pro Leu 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys 100 105 <210> 64 <211> 26 <212> PRT <213> Artificial Sequence <220> <223> L-FR1 of SA3104 <400> 64 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 20 25 <210> 65 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> L-CDR1 of SA3104 <400> 65 Gln Thr Ile Tyr Arg Tyr 1 5 <210> 66 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> L-FR2 of SA3104 <400> 66 Leu Asn Trp Tyr Gln Gln Glu Pro Gly Ala Pro Pro Lys Leu Leu Ile 1 5 10 15 Ser <210> 67 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA3104 <400> 67 Ala Ala Ser 1 <210> 68 <211> 36 <212> PRT <213> Artificial Sequence <220> <223> L-FR3 of SA3104 <400> 68 Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 1 5 10 15 Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala 20 25 30 Thr Tyr Tyr Cys 35 <210> 69 <211> 9 <212> PRT <213> Artificial Sequence <220> < 223> L-CDR3 of SA3104 <400> 69 Gln Gln Leu Lys Asn Tyr Pro Leu Thr 1 5 <210> 70 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-FR4 of SA3104 <400> 70 Phe Gly Gly Gly Thr Lys Val Asp Ile Lys 1 5 10 <210> 71 <211> 360 <212> DNA <213> Artificial Sequence <220> <223> Variable region of heavy chain gene of SA3104 <400 > 71 caggtgcagc tggtacagtc tgggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgtgcag cctctggatt caccttcagt agctatgcta tgcactgggt ccgccaggct 120 ccaggcaagg ggctggagtg ggtggcagtt atatcatatg atggaag taa taaatactat 180 gcagactccg tgaagggccg attcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagtctgag agccgaggac acggccgtgt attactgtgc gagaggttcg 300 gggaggcatt atcaaccctt ggaccactgg ggccagggaa ccct ggtcac cgtctcctca 360 360 <210> 72 < 211> 321 <212> DNA <213> Artificial Sequence <220> <223> Variable region of light chain gene of SA3104 <400> 72 gacatccaga tgacccagtc tccatcctcc ctgtctgcat ctgtcggaga cagagtcacc 60 atcacttgtc gggcaagtca gaccatctac aggtatttga attggtatca acaggaacca 120 ggggcacccc ctaagctact gatctctgct gcatccactt tacaaagtgg ggtcccatca 180 aggttcagtg gcagtgggtc tgggacagat ttcactctca ccatcagcag cctgcagcct 240 gaagattttg caacttacta ctgtcaacag cttaaaaatt atccactcac tttcggcgga 300 gggaccaagg tggatatcaa a 321 <210> 73 <211> 12 0 <212> PRT <213> Artificial Sequence <220> <223> Variable region of heavy chain of SA3105 < 400> 73 Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Arg Ser Thr Tyr Asn Tyr 20 25 30 Ala Phe Tyr Trp Val Arg Gln Ala Pro Gly His Gly Leu Glu Trp Met 35 40 45 Gly Gly Ile Ile Pro Ile Phe Gly Ala Thr Asn Tyr Ala Gln Lys Phe 50 55 60 Gln Gly Arg Val Thr Ile Thr Ala Asp Glu Ser Thr Asn Thr Ala Tyr 65 70 75 80 Met Glu Val Thr Asn Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Lys Gly Ser Gly Asn Tyr Tyr Tyr Gly Met Asp Val Trp Gly Gln 100 105 110 Gly Thr Thr Val Thr Val Ser Ser 115 120 <210 > 74 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> H-FR1 of SA3105 <400> 74 Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser 20 25 <210> 75 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR1 of SA3105 <400> 75 Gly Arg Ser Thr Tyr Asn Tyr Ala 1 5 <210> 76 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA3105 <400> 76 Phe Tyr Trp Val Arg Gln Ala Pro Gly His Gly Leu Glu Trp Met Gly 1 5 10 15 Gly <210> 77 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR2 of SA3105 <400> 77 Ile Ile Pro Ile Phe Gly Ala Thr 1 5 <210 > 78 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> H-FR3 of SA3105 <400> 78 Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Ile Thr Ala Asp Glu 1 5 10 15 Ser Thr Asn Thr Ala Tyr Met Glu Val Thr Asn Leu Arg Ser Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 79 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> H -CDR3 of SA3105 <400> 79 Ala Lys Gly Ser Gly Asn Tyr Tyr Tyr Gly Met Asp Val 1 5 10 <210> 80 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-FR4 of SA3105 <400> 80 Trp Gly Gln Gly Thr Val Thr Val Ser Ser 1 5 10 <210> 81 <211> 107 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA3105 <400> 81 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 Ser Val Gly Thr Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 35 40 45 Ser Ala Ala Ser Ser Leu His Pro 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 Asp Ser Phe Pro Tyr 85 90 95 Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 100 105 <210> 82 <211> 26 <212> PRT <213> Artificial Sequence <220> <223> L-FR1 of SA3105 <400> 82 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 20 25 <210> 83 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> L-CDR1 of SA3105 <400> 83 Gln Ser Val Gly Thr Trp 1 5 <210> 84 <211> 17 <212> PRT < 213> Artificial Sequence <220> <223> L-FR2 of SA3105 <400> 84 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Arg Ala Pro Lys Leu Leu Ile 1 5 10 15 Ser <210> 85 <211> 3 <212 > PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA3105 <400> 85 Ala Ala Ser 1 <210> 86 <211> 36 <212> PRT <213> Artificial Sequence <220> <223> L -FR3 of SA3105 <400> 86 Ser Leu His Pro Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 1 5 10 15 Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala 20 25 30 Thr Tyr Tyr Cys 35 <210> 87 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> L-CDR3 of SA3105 <400> 87 Gln Gln Ala Asp Ser Phe Pro Tyr Thr 1 5 <210> 88 < 211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-FR4 of SA3105 <400> 88 Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys 1 5 10 <210> 89 <211> 360 <212 > DNA <213> Artificial Sequence <220> <223> Variable region of heavy chain gene of SA3105 <400> 89 cagatgcagc tggtgcagtc tggggctgag gtgaagaggc ctgggtcctc ggtgaaggtc 60 tcgtgcaagg cttctggaag gtccacctac aactatgctt tctactggg t tcgacaggcc 120 cctggacacg ggcttgagtg gatgggcggg atcatcccta tctttggggc aacaaactac 180 gcacagaagt tccagggcag agtcacgatt accgcggacg aatccacgaa cacagcctac 240 atggaggtga cgaacctgag atctgaggac acggccgtgt attactgtgc aaaaggttcg 300 ggtaactact actacggtat ggacgtctgg ggccaaggga ccacggtcac cgtctcctca 360 360 <210> 90 <211> 321 <212> DNA <213> Artificial Sequence <220> <223> Variable region of light chain gene of SA3105 < 400> 90 gacatccaga tgacccagtc tccatcttcc gtgtctgcat ctgtaggaga cagagtcacc 60 atcacttgtc gggcgagtca gagtgttggc acctggttag cctggtatca gcagaaacca 120 gggagggccc ctaagctcct gatctctgct gcatccagtt tgcaccctgg gg tcccatca 180 aggttcagcg gcagtggatc tgggacagat ttcactctca ccatcagcag cctgcagcct 240 gaagattttg caacttacta ttgtcaacag gctgacagtt tcccgtacac ttttggccag 300 gggaccaagc tggaaatcaa a 321 <210> 91 <21 1> 118 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA2608 <400> 91 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Pro Pro Gly Gly 1 5 10 15 Ser Val Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Gly 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 Leu Ile Ser Gly Asp Gly Gly Thr Thr Tyr Tyr Gly Asp Ser Val 50 55 60 Lys Gly Arg Tyr Thr Ile Ser Arg Asp Asn Ser 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 Arg Gly Gly Arg Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr 100 105 110 Thr Val Thr Val Ser Ser 115 <210> 92 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> H-FR1 of SA3106 <400> 92 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Pro Pro Pro Gly Gly 1 5 10 15 Ser Val Arg Leu Ser Cys Ala Ala Ser 20 25 <210> 93 <211> 8 <212> PRT <213> Artificial Sequence <220> < 223> H-CDR1 of SA3106 <400> 93 Gly Phe Thr Phe Gly Asp Tyr Ala 1 5 <210> 94 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA3106 < 400> 94 Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 1 5 10 15 Leu <210> 95 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA2608 <400> 95 Ile Ser Gly Asp Gly Gly Thr Thr 1 5 <210> 96 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> H-FR3 of SA3106 <400> 96 Tyr Tyr Gly Asp Ser Val Lys Gly Arg Tyr Thr Ile Ser Arg Asp Asn 1 5 10 15 Ser Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 97 <211 > 11 <212> PRT <213> Artificial Sequence <220> <223> H-CDR3 of SA3106 <400> 97 Ala Arg Gly Gly Arg Val Tyr Gly Met Asp Val 1 5 10 <210> 98 <211> 11 <212 > PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA2608 <400> 98 Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 1 5 10 <210> 99 <211> 107 <212> PRT <213 > Artificial Sequence <220> <223> Variable region of light chain of SA3106 <400> 99 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asn Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Val Trp 20 25 30 Leu Ala Trp Phe Gln Gln Lys Pro Glu Thr Ala Pro Lys Ser Leu Ile 35 40 45 Tyr Gly Ser Ser Asn 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 Asn Asn Leu Gln Pro 65 70 75 80 Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Lys Ala Ser Pro Pro 85 90 95 Thr Phe Gly Gly Gly Thr Lys Val Asp Ile Lys 100 105 < 210> 100 <211> 26 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA2608 <400> 100 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly 1 5 10 15 Asn Arg Val Thr Ile Thr Cys Arg Ala Ser 20 25 <210> 101 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA2608 <400> 101 Gln Gly Ile Ser Val Trp 1 5 <210> 102 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> L-FR2 of SA3106 <400> 102 Leu Ala Trp Phe Gln Gln Lys Pro Glu Thr Ala Pro Lys Ser Leu Ile 1 5 10 15 Tyr <210> 103 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA3106 <400> 103 Gly Ser Ser 1 <210> 104 <211> 36 <212> PRT <213> Artificial Sequence <220> <223> L-FR3 of SA3106 <400> 104 Asn Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 1 5 10 15 Thr Asp Phe Thr Leu Thr Ile Asn Asn Leu Gln Pro Glu Asp Phe Ala 20 25 30 Thr Tyr Tyr Cys 35 <210> 105 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> L-CDR3 of SA3106 <400> 105 Gln Gln Tyr Lys Ala Ser Pro Pro Thr 1 5 <210> 106 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-FR4 of SA3106 <400> 106 Phe Gly Gly Gly Thr Lys Val Asp Ile Lys 1 5 10 <210> 107 <211> 354 <212> DNA <213> Artificial Sequence <220> <223> Variable region of heavy chain gene of SA3106 <400> 107 caggtgcagc tggtggagtc tggtggaggc gtggttccgc ctggggggtc cgtgagact c 60 tcctgtgcag cctctggatt cacctttggt gattatgcca tgcactgggt ccgtcaagct 120 ccagggaagg gtctggagtg ggtctctctt attagtgggg atggcggtac cacatactat 180 ggagactctg tgaagggccg atacaccatc tccagagaca acagcaaaaa ctccctgtat 240 ctgcaaatga acagtctga g agccgaggac acggccgtgt attactgtgc aagagggggc 300 agggtttacg gtatggacgt ctggggccaa gggaccacgg tcaccgtctc ctca 354 <210> 108 <211> 321 <212> DNA <213> Artificial Sequence <220> <223> Variable region of light chain gene of SA3106 <400> 108 gacatccaga tgacccagtc tccatcctca ctgtctgcat ctgtaggaaa cagagtcacc 60 atcacttgtc gggcgagtca gggtattagc gtctggttag cctggtttca gcagaaacca 120 gagacagccc ctaag tccct gatctatggt tcatccaatt tgcaaagtgg ggtcccgtca 180 aggttcagcg gcagtggatc tgggacagat ttcactctca ccattaacaa tctgcagcct 240 gaagattttg caacttatta ctgccaaacaa tataaggcct ctcctccaac tttcggcgga 300 gggaccaagg tggatatcaa a 321 <210> 109 <211> 119 <212> PRT <213> Artificial Sequence <220> <223> Variable region of heavy chain of SA3114 <400> 109 Gln Met Gln Leu Val Glu Ser Gly Gly Gly Leu Ile Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Asp Asp Tyr 20 25 30 Ala Met His Trp Val Arg Gln Gly Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Ser Ile Ser Trp Asn Ser Arg Thr Met 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 Val Tyr Tyr Cys 85 90 95 Ala Arg Thr Lys Gly Phe Pro Gly His Phe His Glu Trp Gly Gln Gly 100 105 110 Thr Leu Val Thr Val Ser Ser 115 <210> 110 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> H-FR1 of SA3114 <400> 110 Gln Met Gln Leu Val Glu Ser Gly Gly Gly Leu Ile Gln Pro Gly Arg 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25 <210> 111 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR1 of SA3114 <400> 111 Gly Phe Ser Phe Asp Asp Tyr Ala 1 5 <210> 112 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA3114 <400> 112 Met His Trp Val Arg Gln Gly Pro Gly Lys Gly Leu Glu Trp Val Ala 1 5 10 15 Ser <210> 113 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR2 of SA3114 <400> 113 Ile Ser Trp Asn Ser Arg Thr Met 1 5 <210> 114 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> H-FR3 of SA3114 <400> 114 Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn 1 5 10 15 Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 115 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> H-CDR3 of SA3114 <400> 115 Ala Arg Thr Lys Gly Phe Pro Gly His Phe His Glu 1 5 10 <210> 116 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-FR4 of SA3114 <400> 116 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 1 5 10 <210> 117 <211> 112 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA3114 <400> 117 Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Gly Ser Pro Gly Lys 1 5 10 15 Thr Val Thr Ile Ser Cys Thr His Ser Ser Gly Ser Phe Ala Asn Asn 20 25 30 Tyr Val Gln Trp Tyr Gln Arg Arg Leu Gly Ser Ala Pro Thr Thr Val 35 40 45 Ile Tyr Gly Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Ile Asp Ser Ser Ser Asn Ser Ala Ser Leu Thr Ile Ser Gly 65 70 75 80 Leu Lys Thr Glu Asp Glu Gly Asp Tyr Tyr Cys Gln Ser Tyr Asp Ser 85 90 95 Arg Asn Arg Asn Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu 100 105 110 <210> 118 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> L-FR1 of SA3114 <400> 118 Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Gly Ser Pro Gly Lys 1 5 10 15 Thr Val Thr Ile Ser Cys Thr His Ser 20 25 <210> 119 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> L-CDR1 of SA3114 <400> 119 Ser Gly Ser Phe Ala Asn Asn Tyr 1 5 <210> 120 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> L-FR2 of SA3114 <400> 120 Val Gln Trp Tyr Gln Arg Arg Leu Gly Ser Ala Pro Thr Thr Val Ile 1 5 10 15 Tyr <210> 121 < 211> 5 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA3114 <400> 121 Gly Asp Asn Gln Arg 1 5 <210> 122 <211> 36 <212> PRT <213> Artificial Sequence <220> <223> L-FR3 of SA3114 <400> 122 Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ile Asp Ser Ser Ser 1 5 10 15 Asn Ser Ala Ser Leu Thr Ile Ser Gly Leu Lys Thr Glu Asp Glu Gly 20 25 30 Asp Tyr Tyr Cys 35 <210> 123 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> L-CDR3 of SA3114 <400> 123 Gln Ser Tyr Asp Ser Arg Asn Arg Asn Tyr Val 1 5 10 <210> 124 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-FR4 of SA3114 <400> 124 Phe Gly Thr Gly Thr Lys Val Thr Val Leu 1 5 10 <210> 125 <211> 357 <212> DNA <213> Artificial Sequence <220> <223> Variable region of heavy chain gene of SA3114 <400> 125 cagatgcagc tggtagagtc tgggggaggc ttgatacagc ctggcaggtc cctgagactc 60 tcctgtgcag cct ctggatt cagcttcgat gattatgcca tgcactgggt ccggcaaggt 120 ccagggaagg gcctggagtg ggtcgcaagt attagttgga atagtcgtac catgggctat 180 gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240 ttgcaaatga acagtctgag agccgaggac acggccgtgt attactgtgc gagaacca aa 300 ggatttcccg gacacttcca tgaatggggt cagggcaccc tggtcaccgt ctcctca 357 <210> 126 <211> 336 <212> DNA <213> Artificial Sequence <220> <223 > Variable region of light chain gene of SA3114 <400> 126 aattttatgc tgactcagcc ccactctgtg tcgggttctc cggggaagac ggtgaccatc 60 tcctgcaccc acagcagtgg cagctttgcc aacaactatg tgcagtggta ccagcggcgc 120 ctgggcagtg ccc ccaccac tgtgatctat ggggataacc aaagaccctc cggggtccct 180 gatcggttct ctggctccat cgacagctcc tccaactctg cctccctcac catctctgga 240 ctgaagactg aagacgaggg tgactactac tgtcagtctt atgatagccg caatcgtaat 300 tatgtcttcg gaact gggac caaggtcacc gtccta 336 <210> 127 <211> 122 <212> PRT <213> Artificial Sequence <220> <223> Variable region of heavy chain of SA3128 <400> 127 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Lys 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Leu Arg Thr Tyr 20 25 30 Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Asn Ile Trp His Asp Gly Ser His Thr Phe Tyr Ala Asp Ser Val 50 55 60 Gln Gly Arg Phe Thr Val Ser Arg Asp Asn Ser Ala Asn Leu Leu Phe 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 Gly Gly Ser Tyr Ser Arg Tyr Ser Asp Ala Phe Asp Ile Trp 100 105 110 Gly Gln Gly Thr Val Ile Thr Val Ser Ser 115 120 <210> 128 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> H-FR1 of SA3128 <400> 128 Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Lys 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25 <210> 129 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR1 of SA3128 <400> 129 Gly Phe Ser Leu Arg Thr Tyr Gly 1 5 <210> 130 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA3128 <400> 130 Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala 1 5 10 15 Asn <210> 131 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR2 of SA3128 <400> 131 Ile Trp His Asp Gly Ser His Thr 1 5 <210> 132 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> H-FR3 of SA3128 <400> 132 Phe Tyr Ala Asp Ser Val Gln Gly Arg Phe Thr Val Ser Arg Asp Asn 1 5 10 15 Ser Ala Asn Leu Leu Phe Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 133 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> H-CDR3 of SA3128 <400> 133 Ala Arg Gly Gly Ser Tyr Ser Arg Tyr Ser Asp Ala Phe Asp Ile 1 5 10 15 <210> 134 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-FR4 of SA3128 <400> 134 Trp Gly Gln Gly Thr Val Ile Thr Val Ser Ser 1 5 10 <210> 135 <211> 108 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA3128 <400> 135 Asp Ile Gln Met 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 Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser 50 55 60 Gly Thr Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu 65 70 75 80 Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro 85 90 95 Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 100 105 <210> 136 <211> 26 <212> PRT <213> Artificial Sequence <220> <223> L-FR1 of SA3128 <400> 136 Asp Ile Gln Met 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 20 25 <210> 137 <211> 7 <212> PRT < 213> Artificial Sequence <220> <223> L-CDR1 of SA3128 <400> 137 Gln Ser Val Ser Ser Ser Tyr 1 5 <210> 138 <211> 17 <212> PRT <213> Artificial Sequence <220> <223 > L-FR2 of SA3128 <400> 138 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile 1 5 10 15 Tyr <210> 139 <211> 3 <212> PRT <213> Artificial Sequence <220 > <223> L-CDR2 of SA3128 <400> 139 Asp Ala Ser 1 <210> 140 <211> 36 <212> PRT <213> Artificial Sequence <220> <223> L-FR3 of SA3128 <400> 140 Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly Thr Gly Ser Gly 1 5 10 15 Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala 20 25 30 Val Tyr Tyr Cys 35 <210> 141 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> L-CDR3 of SA3128 <400> 141 Gln Gln Arg Ser Asn Trp Pro Leu Thr 1 5 <210> 142 <211> 10 <212> PRT <213 > Artificial Sequence <220> <223> L-FR4 of SA3128 <400> 142 Phe Gly Gly Gly Thr Lys Val Glu Ile Lys 1 5 10 <210> 143 <211> 366 <212> DNA <213> Artificial Sequence <220 > <223> Variable region of heavy chain gene of SA3128 <400> 143 caggtgcagc tggtggagtc tgggggtggc gtggtccagc ctgggaagtc cctgagactc 60 tcctgtgcag cgtctggctt cagtctcagg acctacggca tgcactgggt ccgccaggcc 120 ccaggcaa gg ggctggagtg ggtggcaaat atatggcatg atggaagtca cacattttat 180 gcagactccg tgcagggccg attcaccgtc tccagagaca actccgctaa tcttttgttt 240 ctgcaaatga acagtctgag agccgaggac acggccgtgt attactgtgc cagagggggg 300 agttatcca gatatagcga tgcctttgat atctggggcc aagggacagt gatcaccgtc 360 tcctca 366 <210> 144 <211> 324 <212> DNA <213> Artificial Sequence <220> <223> Variable region of light chain gene of SA3128 <400> 144 gacatccaga tgacccagtc tccaggcacc ctgtctttgt ctccagggga aagagccacc 60 ctctcctgca gggccagtca gagtgttagc agcagctact tagcctggta ccagcagaaa 120 cctggccagg ctcccaggct cctcatctat gatgcatcca acagggccac tggcatccca 180 gccaggttca gtggcactgg gtctgggaca gacttcactc tgaccatcag cagcct ggag 240 cctgaggatt ttgcagttta ttactgtcag cagcgtagca actggccgct cactttcggc 300 ggagggacca aggtggaaat caaa 324 <210> 145 <211> 120 <212> PRT <213> Artificial Sequence <220> <223> Variable region of heavy chain of SA3132 <400> 145 Gln Met Gln Leu Val Glu Ser Gly Ala Glu Val Lys Lys Thr Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Ser Leu Ser Glu Leu 20 25 30 Ser Val Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met 35 40 45 Ala Asn Phe Asp Val Glu Asp Gly Glu Thr Ile Tyr Ala Gln Arg Phe 50 55 60 Gln Gly Arg Val Thr Met Ser Leu Asp Thr Ser Thr Asp Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Arg Asp Leu Pro Glu Leu Arg Gly Val Leu Ala Asp Trp Gly Gln 100 105 110 Gly Thr Leu Val Thr Val Ser Ser 115 120 <210> 146 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA2608 <400> 146 Gln Met Gln Leu Val Glu Ser Gly Ala Glu Val Lys Lys Thr Gly Ala 1 5 10 15 Ser Val Lys Val Ser Cys Lys Val Ser 20 25 <210> 147 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H -CDR1 of SA3132 <400> 147 Gly Tyr Ser Leu Ser Glu Leu Ser 1 5 <210> 148 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA3132 <400> 148 Val Tyr Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Ala 1 5 10 15 Asn <210> 149 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR2 of SA3132 < 400> 149 Phe Asp Val Glu Asp Gly Glu Thr 1 5 <210> 150 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> H-FR3 of SA3132 <400> 150 Ile Tyr Ala Gln Arg Phe Gln Gly Arg Val Thr Met Ser Leu Asp Thr 1 5 10 15 Ser Thr Asp Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 151 <211> 13 < 212> PRT <213> Artificial Sequence <220> <223> H-CDR3 of SA3132 <400> 151 Ala Arg Asp Leu Pro Glu Leu Arg Gly Val Leu Ala Asp 1 5 10 <210> 152 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-FR4 of SA3132 <400> 152 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 1 5 10 < 210> 153 <211> 110 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA3132 <400> 153 Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln 1 5 10 15 Ser Ile Thr Ile Ser Cys Thr Gly Thr Ser Ser Asp Val Gly Gly Tyr 20 25 30 Asp Tyr Val Ser Trp Tyr Gln Gln His Pro Asp Lys Ala Pro Lys Leu 35 40 45 Ile Ile Phe Asp Ala Ser Lys Arg Pro Ser Gly Val Ser Asn Arg Phe 50 55 60 Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu 65 70 75 80 Gln Ala Glu Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Thr Arg Ser 85 90 95 Ser Thr Leu Val Ser Ser Tyr Thr Arg Ser Ser Thr Leu Val 100 105 110 <210> 154 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> L-FR1 of SA3132 <400> 154 Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Gly Ser Pro Gly Gln 1 5 10 15 Ser Ile Thr Ile Ser Cys Thr Gly Thr 20 25 <210> 155 <211> 9 <212> PRT <213> Artificial Sequence <220> < 223> L-CDR1 of SA3132 <400> 155 Ser Ser Asp Val Gly Gly Tyr Asp Tyr 1 5 <210> 156 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> L-FR2 of SA3132 <400> 156 Val Ser Trp Tyr Gln Gln His Pro Asp Lys Ala Pro Lys Leu Ile Ile 1 5 10 15 Phe <210> 157 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> L- CDR2 of SA3132 <400> 157 Asp Ala Ser 1 <210> 158 <211> 36 <212> PRT <213> Artificial Sequence <220> <223> L-FR3 of SA3132 <400> 158 Lys Arg Pro Ser Gly Val Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly 1 5 10 15 Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu Gln Ala Glu Asp Glu Ala 20 25 30 Asp Tyr Tyr Cys 35 <210> 159 <211> 10 <212> PRT < 213> Artificial Sequence <220> <223> L-CDR3 of SA3132 <400> 159 Ser Ser Tyr Thr Arg Ser Ser Thr Leu Val 1 5 10 <210> 160 <211> 10 <212> PRT <213> Artificial Sequence < 220> <223> L-FR4 of SA3132 <400> 160 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 1 5 10 <210> 161 <211> 360 <212> DNA <213> Artificial Sequence <220> <223> Variable region of heavy chain gene of SA3132 <400> 161 cagatgcagc tggtggagtc tggggctgag gtgaagaaga ctggggcctc agtgaaggtc 60 tcctgcaagg tttctggata cagcctcagt gaattatccg tgtactgggt gcgacaggct 120 cctggaaaag ggcttgagtg gatggcaaat tttgatgttg aagatggtga aacaatctac 180 gcgcagaggt tccagggcag agtcaccatg tccctggaca catctacaga cacagcctac 240 atggagctga gcagcctgag atctgaggac acggccgtgt attactgtgc gagagactta 300 cctgagcttc ggggagt gct tgccgactgg ggtcagggaa ccctggtcac cgtctcctca 360 360 <210> 162 <211> 330 <212> DNA <213> Artificial Sequence <220> <223> Variable region of light chain gene of SA3132 <400> 162 cagtctgccc tgactcagcc tgcctccgtg tctgggt ctc ctggacagtc gatcaccatc 60 tcctgcactg gaaccagcag tgacgttggt ggttatgact atgtctcctg gtaccaacag 120 catccagaca aagcccccaa actcataatt tttgatgcca gtaagcggcc ctcaggggtt 180 tctaatcgct tctctggctc caagtctggc aacacggcct ccctgaccat ctctgggctc 240 caggctgagg acgaggctga ttattactgc agt tcatata caaggagcag tactttggta 300 ttcggcggag ggaccaagct gaccgtccta 330 <210> 163 <211> 118 <212> PRT <213> Artificial Sequence <220> < 223> Variable region of heavy chain of SA3133 <400> 163 Gln Met Gln Leu Val Gln Ser Gly Gly Lys Leu Val Gln Pro Gly Ser 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ser Phe Asp Asp Tyr 20 25 30 Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ser Ala Ile Ser Gly Ser Gly Gly Ser Thr 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 Gly Gly Arg Val Tyr Gly Met Asp Val Trp Gly Gln Gly Thr 100 105 110 Thr Val Thr Val Ser Ser 115 <210> 164 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> H-FR1 of SA3133 <400> 164 Gln Met Gln Leu Val Gln Ser Gly Gly Lys Leu Val Gln Pro Gly Ser 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25 <210> 165 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR1 of SA3133 <400> 165 Gly Phe Ser Phe Asp Asp Tyr Gly 1 5 <210> 166 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA3133 <400> 166 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 1 5 10 15 Ala <210> 167 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR2 of SA3133 <400> 167 Ile Ser Gly Ser Gly Gly Ser Thr 1 5 <210> 168 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> H-FR3 of SA3133 <400> 168 Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn 1 5 10 15 Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 169 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-CDR3 of SA3133 <400> 169 Ala Arg Gly Gly Arg Val Tyr Gly Met Asp Val 1 5 10 <210> 170 <211> 11 <212> PRT <213> Artificial Sequence <220> < 223> H-FR4 of SA3133 <400> 170 Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser 1 5 10 <210> 171 <211> 107 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA3133 <400> 171 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly 1 5 10 15 Asp Thr Val Thr Ile Thr Cys Arg Ala Ser His Asp Ile Arg Arg Trp 20 25 30 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Glu Val Pro Lys Val Leu Ile 35 40 45 Tyr Ala Ala Ala Val Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Phe Ser Leu Thr Ile Thr Asn Leu Gln Pro 65 70 75 80 Glu Asp Val Ala Thr Tyr Tyr Cys Gln Lys Tyr Asp Ser Val Pro Phe 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 100 105 <210> 172 <211> 26 <212> PRT <213> Artificial Sequence <220> <223> L-FR1 of SA3133 <400> 172 Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly 1 5 10 15 Asp Thr Val Thr Ile Thr Cys Arg Ala Ser 20 25 <210> 173 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> L-CDR1 of SA3133 <400> 173 His Asp Ile Arg Arg Trp 1 5 <210> 174 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> L-FR2 of SA3133 <400> 174 Leu Ala Trp Tyr Gln Gln Lys Pro Gly Glu Val Pro Lys Val Leu Ile 1 5 10 15 Tyr <210> 175 < 211> 3 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA3133 <400> 175 Ala Ala Ala 1 <210> 176 <211> 36 <212> PRT <213> Artificial Sequence <220 > <223> L-FR3 of SA3133 <400> 176 Val Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly 1 5 10 15 Thr Asp Phe Ser Leu Thr Ile Thr Asn Leu Gln Pro Glu Asp Val Ala 20 25 30 Thr Tyr Tyr Cys 35 <210> 177 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> L-CDR3 of SA3133 <400> 177 Gln Lys Tyr Asp Ser Val Pro Phe Thr 1 5 <210> 178 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-FR4 of SA3133 <400> 178 Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys 1 5 10 <210> 179 < 211> 354 <212> DNA <213> Artificial Sequence <220> <223> Variable region of heavy chain gene of SA3133 <400> 179 cagatgcagc tggtgcagtc tgggggaaag ttggtacagc ctggcagttc cctgagactc 60 tcctgtgcag cctccggatt cagctttga t gattatggca tgagctgggt ccgccaggct 120 ccagggaagg ggctggagtg ggtctcagct attagtggta gtggtggtag cacatactac 180 gcagactccg tgaagggccg gttcaccatc tccagagaca attccaagaa cacgctgtat 240 ctgcaaatga acagtctgag agccgaggac acggccgtgt attactgtgc aagagggggc 300 agggtttacg gtatggacgt ctggggccaa gggaccacgg tcaccgtctc ctca 354 <210> 180 <211> 321 <212> DNA <213> Artificial Sequence <220> <223 > Variable region of light chain gene of SA3133 <400> 180 gacatccaga tgacccagtc tccatcttcc gtgtctgcgt ctgtaggaga caccgtcacc 60 atcacttgtc gggcgagtca cgatattcgt aggtggttgg cctggtatca gcagaaacca 120 ggggaagtcc ctaaggtcct g atctatgct gcagccgtct tgcattcagg ggtcccatct 180 cggttcagtg gcagtggatc tgggacagat ttcagtctca ccataactaa cctgcagcct 240 gaagatgttg ccacttatta ctgtcaaaag tatgacagtg tccctttcac tttcggcggg 300 gggaccaagc t ggagatcaa a 321 <210> 181 <211> 118 <212> PRT <213> Artificial Sequence <220> <223> Variable region of heavy chain of SA3140 <400> 181 Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Phe His Asn Tyr 20 25 30 Ala Met Ser 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 Val Tyr Tyr Cys 85 90 95 Ala Gly Leu Lys Gly Met Asn Trp Phe Asp Pro Trp Gly Gln Gly Thr 100 105 110 Leu Val Thr Val Ser Ser 115 <210> 182 <211> 25 <212> PRT <213> Artificial Sequence <220> <223 > H-FR1 of SA3140 <400> 182 Gln Val Gln Leu Val Glu Ser Gly Gly Ala Leu Val Gln Pro Gly Gly 1 5 10 15 Ser Leu Arg Leu Ser Cys Ala Ala Ser 20 25 <210> 183 <211> 8 < 212> PRT <213> Artificial Sequence <220> <223> H-CDR1 of SA3140 <400> 183 Gly Phe Asn Phe His Asn Tyr Ala 1 5 <210> 184 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA3140 <400> 184 Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser 1 5 10 15 Gly <210> 185 <211> 8 <212> PRT <213 > Artificial Sequence <220> <223> H-CDR2 of SA3140 <400> 185 Ile Ser Trp Asn Ser Gly Ser Ile 1 5 <210> 186 <211> 38 <212> PRT <213> Artificial Sequence <220> <223 > H-FR3 of SA3140 <400> 186 Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn 1 5 10 15 Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 187 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-CDR3 of SA3140 <400> 187 Ala Gly Leu Lys Gly Met Asn Trp Phe Asp Pro 1 5 10 <210> 188 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-FR4 of SA3140 <400> 188 Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser 1 5 10 <210 > 189 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA3140 <400> 189 Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Gly Ser Pro Gly Lys 1 5 10 15 Thr Val Ala Ile Ser Cys Thr Arg Ser Ser Gly Ser Phe Ala Asn Asn 20 25 30 Tyr Val Gln Trp Tyr Gln Gln Arg Pro Gly Ser Ala Pro Thr Thr Val 35 40 45 Ile Tyr Gly Asp Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser 50 55 60 Gly Ser Ile Asp Ser Ser Ser Asn Ser Ala Ser Leu Thr Ile Ser Gly 65 70 75 80 Leu Lys Thr Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Tyr Asp Ser 85 90 95 Asn Asn His Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 100 105 110 <210> 190 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> L-FR1 of SA3140 <400> 190 Asn Phe Met Leu Thr Gln Pro His Ser Val Ser Gly Ser Pro Gly Lys 1 5 10 15 Thr Val Ala Ile Ser Cys Thr Arg Ser 20 25 <210> 191 <211> 8 <212> PRT <213> Artificial Sequence <220> < 223> L-CDR1 of SA3140 <400> 191 Ser Gly Ser Phe Ala Asn Asn Tyr 1 5 <210> 192 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> L-FR2 of SA3140 < 400> 192 Val Gln Trp Tyr Gln Gln Arg Pro Gly Ser Ala Pro Thr Thr Val Ile 1 5 10 15 Tyr <210> 193 <211> 5 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA3140 <400> 193 Gly Asp Asn Gln Arg 1 5 <210> 194 <211> 36 <212> PRT <213> Artificial Sequence <220> <223> L-FR3 of SA3140 <400> 194 Pro Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Ile Asp Ser Ser Ser 1 5 10 15 Asn Ser Ala Ser Leu Thr Ile Ser Gly Leu Lys Thr Glu Asp Glu Ala 20 25 30 Asp Tyr Tyr Cys 35 <210> 195 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-CDR3 of SA3140 <400> 195 Gln Ser Tyr Asp Ser Asn Asn His Trp Val 1 5 10 <210> 196 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-FR4 of SA3140 <400> 196 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 1 5 10 <210> 197 <211> 354 <212> DNA <213> Artificial Sequence <220> < 223> Variable region of heavy chain gene of SA3140 <400> 197 caggtgcagc tggtagagtc tgggggagcc ttggtacagc ccgggggatc cctgaggctc 60 tcctgtgcag cctctggatt caactttcat aactatgcca tgagttgggt ccgccaggct 120 ccagggaagg ggctgg agtg ggtctcaggt attagttgga atagtggtag cataggctat 180 gcggactctg tgaagggccg attcaccatc tccagagaca acgccaagaa ctccctgtat 240 ctgcaaatga acagtctgag agccgaggac acggccgtgt attactgtgc gggactcaaa 300 ggcatgaact ggttcgaccc ctggggccag ggaaccctgg tcaccgtctc ctca 354 <210> 198 <211> 333 <212> DNA <213> Artificial Sequence <220> <223> Variable region of light chain gene of SA3140 <400> 198 aattttatgc tgactcagcc ccactctgtg tc gggttctc cggggaagac ggtggccatc 60 tcctgcaccc gcagcagtgg cagctttgcc aacaactatg tgcagtggta ccagcagcgc 120 ccgggcagtg cccccaccac tgtgatctat ggggataacc aaagaccctc tggggtccct 180 gatcggttct ctggctccat cgacagctcc tccaactctg cctccctcac catctctgga 240 ctgaagactg agg acgaggc tgactactac tgtcagtctt atgatagcaa caatcattgg 300 gtcttcggcg gagggaccaa gctgaccgtc cta 333 <210> 199 <211> 118 <212> PRT <213> Artificial Sequence <220 > <223> Variable region of heavy chain of SA3389 <400> 199 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser Gly Gly Thr Phe Ser Thr Tyr 20 25 30 Ala Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met 35 40 45 Gly Arg Ile Ile Pro Phe Val Gly Thr Val Asp Tyr Ala Gln Lys Phe 50 55 60 Gln Asp Arg Val Thr Ile Thr Ala Asp Lys Ser Thr Asn Thr Ala Tyr 65 70 75 80 Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Val Arg Asp Gly Gly Arg Ser Tyr Phe Asp Ser Trp Gly Pro Gly Ile 100 105 110 Leu Val Thr Val Ser Ser 115 <210> 200 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> H-FR1 of SA3389 <400> 200 Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Arg Pro Gly Ser 1 5 10 15 Ser Val Lys Val Ser Cys Lys Ala Ser 20 25 <210> 201 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR1 of SA3389 <400 > 201 Gly Gly Thr Phe Ser Thr Tyr Ala 1 5 <210> 202 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA3389 <400> 202 Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly 1 5 10 15 Arg <210> 203 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR2 of SA3389 <400> 203 Ile Ile Pro Phe Val Gly Thr Val 1 5 <210> 204 <211> 38 <212> PRT <213> Artificial Sequence <220> <223> H-FR3 of SA3389 <400> 204 Asp Tyr Ala Gln Lys Phe Gln Asp Arg Val Thr Ile Thr Ala Asp Lys 1 5 10 15 Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 205 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-CDR3 of SA3389 <400> 205 Val Arg Asp Gly Gly Arg Ser Tyr Phe Asp Ser 1 5 10 <210> 206 <211> 11 <212> PRT <213> Artificial Sequence <220 > <223> H-FR4 of SA3389 <400> 206 Trp Gly Pro Gly Ile Leu Val Thr Val Ser Ser 1 5 10 <210> 207 <211> 110 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA3389 <400> 207 Gln Phe Val Leu Thr Gln Pro Pro Ser Val Ser Ala Ala Pro Gly Gln 1 5 10 15 Asp Val Ile Ile Ser Cys Ser Gly Asn Thr Ser Asn Ile Gly Ser Asn 20 25 30 Leu Val Ser Trp Phe Gln Gln Phe Pro Glu Thr Ala Pro Lys Leu Leu 35 40 45 Ile Tyr Asp Asn His Lys Arg Pro Ser Gly Ile Ser Asp Arg Phe Ser 50 55 60 Gly Thr Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln 65 70 75 80 Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Val Ala Trp Asp Asp Ser Leu 85 90 95 Asn Gly Tyr Val Phe Gly Thr Gly Thr Lys Val Thr Val Leu 100 105 110 <210> 208 <211 > 25 <212> PRT <213> Artificial Sequence <220> <223> L-FR1 of SA3389 <400> 208 Gln Phe Val Leu Thr Gln Pro Pro Ser Val Ser Ala Ala Pro Gly Gln 1 5 10 15 Asp Val Ile Ile Ser Cys Ser Gly Asn 20 25 <210> 209 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> L-CDR1 of SA3389 <400> 209 Thr Ser Asn Ile Gly Ser Asn Leu 1 5 < 210> 210 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> L-FR2 of SA3389 <400> 210 Val Ser Trp Phe Gln Gln Phe Pro Glu Thr Ala Pro Lys Leu Leu Ile 1 5 10 15 Tyr <210> 211 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA3389 <400> 211 Asp Asn His 1 <210> 212 <211> 36 <212> PRT <213> Artificial Sequence <220> <223> L-FR3 of SA3389 <400> 212 Lys Arg Pro Ser Gly Ile Ser Asp Arg Phe Ser Gly Thr Lys Ser Gly 1 5 10 15 Thr Ser Ala Ser Leu Ala Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala 20 25 30 Asp Tyr Tyr Cys 35 <210> 213 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> L-CDR3 of SA3389 <400> 213 Val Ala Trp Asp Asp Ser Leu Asn Gly Tyr Val 1 5 10 <210> 214 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-FR4 of SA3389 <400> 214 Phe Gly Thr Gly Thr Lys Val Thr Val Leu 1 5 10 <210> 215 <211> 354 <212> DNA <213> Artificial Sequence <220> <223> Variable region of heavy chain gene of SA3389 <400> 215 caggtgcagc tggtacagtc tggggctgag gtgaagaggc ctgggtcctc ggtgaaggtc 60 tcctgcaagg cttctggagg caccttcagc acctatgcta tcagctgggt gcgacaggcc 120 cctggacaag ggcttgagtg gatgggaagg atcatccctt tcgttggtac agtagactac 180 gcacagaagt tccaggacag agtcacaatt accgcggaca aatccacgaa cacagcctac 240 atggagctga gcagcctgag atctga ggac acggccgtgt attactgtgt gagagatggg 300 ggccgtagtt attttgactc ctggggcccg ggaatcctgg tcaccgtctc ctca 354 <210> 216 <211> 330 <212> DNA <213> Artificial Sequence < 220> <223> Variable region of light chain gene of SA3389 <400> 216 cagttcgtgc tgactcagcc gccctcagtc tctgcggccc cagggcagga cgtcatcatc 60 tcttgctctg gaaacacttc caacattggg agtaaccttg tctcctggtt ccagcaattc 120 ccaga gacag cccccaaact cctgatttat gacaatcata agcgaccctc aggaatttct 180 gaccgattct ctggcaccaa gtctggtacc tcagcctccc tggccatcag tgggctccag 240 tctgaggatg aggctgatta ttactgtgtg gcatgggatg acagtctgaa tggttatgtc 300 ttcggaactg ggaccaaggt caccgtccta 330 <210> 217 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> Variable region of heavy chain of SA3399 <400> 217 Gln 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 Ser Ala Ser Gly Phe Thr Phe Asn Lys Tyr 20 25 30 Gly Leu His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val 35 40 45 Ala Val Ile Ser Pro Ser Gly Ser Leu Gln Tyr Tyr Tyr Thr Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Asn Asn Thr Leu His 65 70 75 80 Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys 85 90 95 Ala Ala Gly Leu Ile Gly Gly Ala Thr Ala Ala Phe Asp Asn Trp Gly 100 105 110 Gln Gly Thr Pro Ile Thr Val Ser Ser 115 120 <210> 218 <211> 25 <212> PRT <213 > Artificial Sequence <220> <223> H-FR1 of SA3399 <400> 218 Gln 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 Ser Ala Ser 20 25 < 210> 219 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR1 of SA3399 <400> 219 Gly Phe Thr Phe Asn Lys Tyr Gly 1 5 <210> 220 <211> 17 < 212> PRT <213> Artificial Sequence <220> <223> H-FR2 of SA3399 <400> 220 Leu His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala 1 5 10 15 Val <210> 221 <211 > 8 <212> PRT <213> Artificial Sequence <220> <223> H-CDR2 of SA3399 <400> 221 Ile Ser Pro Ser Gly Ser Leu Gln 1 5 <210> 222 <211> 38 <212> PRT <213 > Artificial Sequence <220> <223> H-FR3 of SA3399 <400> 222 Tyr Tyr Thr Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn 1 5 10 15 Ser Asn Asn Thr Leu His Leu Gln Met Asn Ser Leu Arg Ala Glu Asp 20 25 30 Thr Ala Val Tyr Tyr Cys 35 <210> 223 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> H-CDR3 of SA3399 <400> 223 Ala Ala Gly Leu Ile Gly Gly Ala Thr Ala Ala Phe Asp Asn 1 5 10 <210> 224 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> H-FR4 of SA3399 <400> 224 Trp Gly Gln Gly Thr Pro Ile Thr Val Ser Ser 1 5 10 <210> 225 <211> 110 <212> PRT <213> Artificial Sequence <220> <223> Variable region of light chain of SA3399 <400> 225 Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Arg Ser Leu Gly Gln 1 5 10 15 Ser Ile Thr Ile Ser Cys Thr Gly Ser Ser Ser Asp Ile Gly Asp Tyr 20 25 30 Ser Phe Val Ser Trp Tyr Arg Gln His Pro Asn Arg Ala Pro Thr Leu 35 40 45 Met Ile Tyr Asp Val Tyr Lys Arg Pro Ser Gly Val Ser Asn Arg Phe 50 55 60 Ser Gly Ser Lys Ser Gly Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu 65 70 75 80 Gln Ala Gly Asp Glu Ala Asp Tyr Tyr Cys Ser Ser Tyr Ala Thr Asp 85 90 95 Arg Thr Leu Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 100 105 110 <210> 226 <211> 25 <212> PRT <213> Artificial Sequence <220> <223> L -FR1 of SA3399 <400> 226 Gln Ser Ala Leu Thr Gln Pro Ala Ser Val Ser Arg Ser Leu Gly Gln 1 5 10 15 Ser Ile Thr Ile Ser Cys Thr Gly Ser 20 25 <210> 227 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> L-CDR1 of SA3399 <400> 227 Ser Ser Asp Ile Gly Asp Tyr Ser Phe 1 5 <210> 228 <211> 17 <212> PRT <213> Artificial Sequence < 220> <223> L-FR2 of SA3399 <400> 228 Val Ser Trp Tyr Arg Gln His Pro Asn Arg Ala Pro Thr Leu Met Ile 1 5 10 15 Tyr <210> 229 <211> 3 <212> PRT <213> Artificial Sequence <220> <223> L-CDR2 of SA3399 <400> 229 Asp Val Tyr 1 <210> 230 <211> 36 <212> PRT <213> Artificial Sequence <220> <223> L-FR3 of SA3399 < 400> 230 Lys Arg Pro Ser Gly Val Ser Asn Arg Phe Ser Gly Ser Lys Ser Gly 1 5 10 15 Asn Thr Ala Ser Leu Thr Ile Ser Gly Leu Gln Ala Gly Asp Glu Ala 20 25 30 Asp Tyr Tyr Cys 35 <210> 231 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-CDR3 of SA3399 <400> 231 Ser Ser Tyr Ala Thr Asp Arg Thr Leu Val 1 5 10 <210> 232 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> L-FR4 of SA3399 <400> 232 Phe Gly Gly Gly Thr Lys Leu Thr Val Leu 1 5 10 <210> 233 <211> 363 <212> DNA < 213> Artificial Sequence <220> <223> Variable region of heavy chain gene of SA3399 <400> 233 caggtgcagc tggtggagtc ggggggaggc gtggtccagc ctgggaggtc cctgagactc 60 tcctgttcag cctctggatt caccttcaat aaatatggcc ttcattgggt ccgc caggct 120 ccgggcaagg ggctggagtg ggtggcagtt atttcaccta gtggaagtct acagtactac 180 acagactccg tgaagggccg attcaccatc tccagagaca attccaaacaa cactctacat 240 ctgcaaatga acagtctgag agccgaggac acggccgtgt attactgtgc ggctgggttg 300 attgggggcg ctaccgcggc ctttgacaac tggggccagg gaaccccgat caccgtctcc 360 tca 363 <210> 234 <211> 330 <212> DNA < 213> Artificial Sequence <220> <223> Variable region of light chain gene of SA3399 <400> 234 cagtctgccc tgactcagcc tgcctccgtg tctaggtctc ttggacagtc gatcaccatc 60 tcctgcactg gaagcagcag tgacattggt gattacagct ttgtctcctg gtaccggcaa 120 caccccaaca gagcccccac actcatgatt tatgatgtct ataagcggcc ctcagg ggtt 180 tctaatcgct tctctgggtc gaagtctggc aacacggcct ccctgacaat ctctgggctc 240 caggctgggg acgaggctga ttactactgc tcctcatatg caactgatag gactttggtc 300 ttcggcggag ggacaaagct gaccgtccta 330 <210> 235 < 211> 1327 <212 > PRT <213> Homo sapiens <400> 235 Met Thr Leu Asp Arg Pro Gly Glu Gly Ala Thr Met Leu Lys Thr Phe 1 5 10 15 Thr Val Leu Leu Phe Cys Ile Leu Met Asp Pro Gln Pro Glu Leu Trp 20 25 30 Ile Glu Ser Asn Tyr Pro Gln Ala Pro Trp Glu Asn Ile Thr Leu Trp 35 40 45 Cys Arg Ser Pro Ser Arg Ile Ser Ser Lys Phe Leu Leu Leu Lys Asp 50 55 60 Lys Thr Gln Met Thr Trp Ile Arg Pro Ser His Lys Thr Phe Gln Val 65 70 75 80 Ser Phe Leu Ile Gly Ala Leu Thr Glu Ser Asn Ala Gly Leu Tyr Arg 85 90 95 Cys Cys Tyr Trp Lys Glu Thr Gly Trp Ser Lys Pro Ser Lys Val Leu 100 105 110 Glu Leu Glu Ala Pro Gly Gln Leu Pro Lys Pro Ile Phe Trp Ile Gln 115 120 125 Ala Glu Thr Pro Ala Leu Pro Gly Cys Asn Val Asn Ile Leu Cys His 130 135 140 Gly Trp Leu Gln Asp Leu Val Phe Met Leu Phe Lys Glu Gly Tyr Ala 145 150 155 160 Glu Pro Val Asp Tyr Gln Val Pro Thr Gly Thr Met Ala Ile Phe Ser 165 170 175 Ile Asp Asn Leu Thr Pro Glu Asp Glu Gly Val Tyr Ile Cys Arg Thr 180 185 190 His Ile Gln Met Leu Pro Thr Leu Trp Ser Glu Pro Ser Asn Pro Leu 195 200 205 Lys Leu Val Val Ala Gly Leu Tyr Pro Lys Pro Thr Leu Thr Ala His 210 215 220 Pro Gly Pro Ile Met Ala Pro Gly Glu Ser Leu Asn Leu Arg Cys Gln 225 230 235 240 Gly Pro Ile Tyr Gly Met Thr Phe Ala Leu Met Arg Val Glu Asp Leu 245 250 255 Glu Lys Ser Phe Tyr His Lys Lys Thr Ile Lys Asn Glu Ala Asn Phe 260 265 270 Phe Phe Gln Ser Leu Lys Ile Gln Asp Thr Gly His Tyr Leu Cys Phe 275 280 285 Tyr Tyr Asp Ala Ser Tyr Arg Gly Ser Leu Leu Ser Asp Val Leu Lys 290 295 300 Ile Trp Val Thr Asp Thr Phe Pro Lys Thr Trp Leu Leu Ala Arg Pro 305 310 315 320 Ser Ala Val Val Gln Met Gly Gln Asn Val Ser Leu Arg Cys Arg Gly 325 330 335 Pro Val Asp Gly Val Gly Leu Ala Leu Tyr Lys Lys Gly Glu Asp Lys 340 345 350 Pro Leu Gln Phe Leu Asp Ala Thr Ser Ile Asp Asp Asn Thr Ser Phe 355 360 365 Phe Leu Asn Asn Val Thr Tyr Ser Asp Thr Gly Ile Tyr Ser Cys His 370 375 380 Tyr Leu Leu Thr Trp Lys Thr Ser Ile Arg Met Pro Ser His Asn Thr 385 390 395 400 Val Glu Leu Met Val Val Asp Lys Pro Pro Lys Pro Ser Leu Ser Ala 405 410 415 Trp Pro Ser Thr Val Phe Lys Leu Gly Lys Ala Ile Thr Leu Gln Cys 420 425 430 Arg Val Ser His Pro Val Leu Glu Phe Ser Leu Glu Trp Glu Glu Arg 435 440 445 Glu Thr Phe Gln Lys Phe Ser Val Asn Gly Asp Phe Ile Ile Ser Asn 450 455 460 Val Asp Gly Lys Gly Thr Gly Thr Tyr Ser Cys Ser Tyr Arg Val Glu 465 470 475 480 Thr His Pro Asn Ile Trp Ser His Arg Ser Glu Pro Leu Lys Leu Met 485 490 495 Gly Pro Ala Gly Tyr Leu Thr Trp Asn Tyr Val Leu Asn Glu Ala Ile 500 505 510 Arg Leu Ser Leu Ile Met Gln Leu Val Ala Leu Leu Leu Val Val Leu 515 520 525 Trp Ile Arg Trp Lys Cys Arg Arg Leu Arg Ile Arg Glu Ala Trp Leu 530 535 540 Leu Gly Thr Ala Gln Gly Val Thr Met Leu Phe Ile Val Thr Ala Leu 545 550 555 560 Leu Cys Cys Gly Leu Cys Asn Gly Val Leu Ile Glu Glu Thr Glu Ile 565 570 575 Val Met Pro Thr Pro Lys Pro Glu Leu Trp Ala Glu Thr Asn Phe Pro 580 585 590 Leu Ala Pro Trp Lys Asn Leu Thr Leu Trp Cys Arg Ser Pro Ser Gly 595 600 605 Ser Thr Lys Glu Phe Val Leu Leu Lys Asp Gly Thr Gly Trp Ile Ala 610 615 620 Thr Arg Pro Ala Ser Glu Gln Val Arg Ala Ala Phe Pro Leu Gly Ala 625 630 635 640 Leu Thr Gln Ser His Thr Gly Ser Tyr His Cys His Ser Trp Glu Glu 645 650 655 Met Ala Val Ser Glu Pro Ser Glu Ala Leu Glu Leu Val Gly Thr Asp 660 665 670 Ile Leu Pro Lys Pro Val Ile Ser Ala Ser Pro Thr Ile Arg Gly Gln 675 680 685 Glu Leu Gln Leu Arg Cys Lys Gly Trp Leu Ala Gly Met Gly Phe Ala 690 695 700 Leu Tyr Lys Glu Gly Glu Gln Glu Pro Val Gln Gln Leu Gly Ala Val 705 710 715 720 Gly Arg Glu Ala Phe Phe Thr Ile Gln Arg Met Glu Asp Lys Asp Glu 725 730 735 Gly Asn Tyr Ser Cys Arg Thr His Thr Glu Lys Arg Pro Phe Lys Trp 740 745 750 Ser Glu Pro Ser Glu Pro Leu Glu Leu Val Ile Lys Glu Met Tyr Pro 755 760 765 Lys Pro Phe Phe Lys Thr Trp Ala Ser Pro Val Val Thr Pro Gly Ala 770 775 780 Arg Val Thr Phe Asn Cys Ser Thr Pro His Gln His Met Ser Phe Ile 785 790 795 800 Leu Tyr Lys Asp Gly Ser Glu Ile Ala Ser Ser Asp Arg Ser Trp Ala 805 810 815 Ser Pro Gly Ala Ser Ala Ala His Phe Leu Ile Ile Ser Val Gly Ile 820 825 830 Gly Asp Gly Gly Asn Tyr Ser Cys Arg Tyr Tyr Asp Phe Ser Ile Trp 835 840 845 Ser Glu Pro Ser Asp Pro Val Glu Leu Val Val Thr Glu Phe Tyr Pro 850 855 860 Lys Pro Thr Leu Leu Ala Gln Pro Gly Pro Val Val Phe Pro Gly Lys 865 870 875 880 Ser Val Ile Leu Arg Cys Gln Gly Thr Phe Gln Gly Met Arg Phe Ala 885 890 895 Leu Leu Gln Glu Gly Ala His Val Pro Leu Gln Phe Arg Ser Val Ser 900 905 910 Gly Asn Ser Ala Asp Phe Leu Leu His Thr Val Gly Ala Glu Asp Ser 915 920 925 Gly Asn Tyr Ser Cys Ile Tyr Tyr Glu Thr Thr Met Ser Asn Arg Gly 930 935 940 Ser Tyr Leu Ser Met Pro Leu Met Ile Trp Val Thr Asp Thr Phe Pro 945 950 955 960 Lys Pro Trp Leu Phe Ala Glu Pro Ser Ser Val Val Pro Met Gly Gln 965 970 975 Asn Val Thr Leu Trp Cys Arg Gly Pro Val His Gly Val Gly Tyr Ile 980 985 990 Leu His Lys Glu Gly Glu Ala Thr Ser Met Gln Leu Trp Gly Ser Thr 995 1000 1005 Ser Asn Asp Gly Ala Phe Pro Ile Thr Asn Ile Ser Gly Thr Ser Met 1010 1015 1020 Gly Arg Tyr Ser Cys Cys Tyr His Pro Asp Trp Thr Ser Ser Ile Lys 1025 1030 1035 1040 Ile Gln Pro Ser Asn Thr Leu Glu Leu Leu Val Thr Gly Leu Leu Pro 1045 1050 1055 Lys Pro Ser Leu Leu Ala Gln Pro Gly Pro Met Val Ala Pro Gly Glu 1060 1065 1070 Asn Met Thr Leu Gln Cys Gln Gly Glu Leu Pro Asp Ser Thr Phe Val 1075 1080 1085 Leu Leu Lys Glu Gly Ala Gln Glu Pro Leu Glu Gln Gln Arg Pro Ser 1090 1095 1100 Gly Tyr Arg Ala Asp Phe Trp Met Pro Ala Val Arg Gly Glu Asp Ser 1105 1110 1115 1120 Gly Ile Tyr Ser Cys Val Tyr Tyr Leu Asp Ser Thr Pro Phe Ala Ala 1125 1130 1135 Ser Asn His Ser Asp Ser Leu Glu Ile Trp Val Thr Asp Lys Pro Pro Pro 1140 1145 1150 Lys Pro Ser Leu Ser Ala Trp Pro Ser Thr Met Phe Lys Leu Gly Lys 1155 1160 1165 Asp Ile Thr Leu Gln Cys Arg Gly Pro Leu Pro Gly Val Glu Phe Val 1170 1175 1180 Leu Glu His Asp Gly Glu Glu Ala Pro Gln Gln Phe Ser Glu Asp Gly 1185 1190 1195 1200 Asp Phe Val Ile Asn Asn Val Glu Gly Lys Gly Ile Gly Asn Tyr Ser 1205 1210 1215 Cys Ser Tyr Arg Leu Gln Ala Tyr Pro Asp Ile Trp Ser Glu Pro Ser 1220 1225 1230 Asp Pro Leu Glu Leu Val Gly Ala Ala Gly Pro Val Ala Gln Glu Cys 1235 1240 1245 Thr Val Gly Asn Ile Val Arg Ser Ser Leu Ile Val Val Val Val Val 1250 1255 1260 Ala Leu Gly Val Val Leu Ala Ile Glu Trp Lys Lys Trp Pro Arg Leu 1265 1270 1275 1280 Arg Thr Arg Gly Ser Glu Thr Asp Gly Arg Asp Gln Thr Ile Ala Leu 1285 1290 1295 Glu Glu Cys Asn Gln Glu Gly Glu Pro Gly Thr Pro Ala Asn Ser Pro 1300 1305 1310Ser Ser Thr Ser Gln Arg Ile Ser Val Glu Leu Pro Val Pro Ile 1315 1320 1325

Claims (28)

A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 3, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 5, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 7; and
An antibody specific for IGSF1 comprising a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 11, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 13, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 15 or fragments thereof. According to paragraph 2,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 1;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 9. A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 21, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 23, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 25; and
An antibody or fragment thereof specific for IGSF1, comprising a light chain variable region comprising light chain CDR1 of SEQ ID NO: 29, light chain CDR2 of SEQ ID NO: 31, and light chain CR3 of SEQ ID NO: 33. According to paragraph 3,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 19;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 27. A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 39, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 41, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 43; and
An antibody or fragment thereof specific for IGSF1, comprising a light chain variable region comprising light chain CDR1 of SEQ ID NO: 47, light chain CDR2 of SEQ ID NO: 49, and light chain CR3 of SEQ ID NO: 51. According to clause 5,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 37;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 45. A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 57, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 59, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 61; and
An antibody or fragment thereof specific for IGSF1 comprising a light chain variable region comprising light chain CDR1 of SEQ ID NO: 65, light chain CDR2 of SEQ ID NO: 67, and light chain CR3 of SEQ ID NO: 69. In clause 7,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 55;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 63. A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 75, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 77, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 79; and
An antibody specific for IGSF1 comprising a light chain variable region comprising light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 83, light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 85, and light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 87 or fragments thereof. According to clause 9,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 73;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 81. A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 93, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 95, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 97; and
An antibody specific for IGSF1 comprising a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 101, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 103, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 105 or fragments thereof. According to clause 11,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 91;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 99. A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 111, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 113, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 115; and
An antibody specific for IGSF1 comprising a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 119, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 121, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 123 or fragments thereof. According to clause 13,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 109;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 117. A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 129, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 131, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 133; and
An antibody specific for IGSF1 comprising a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 137, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 139, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 141 or fragments thereof. According to clause 15,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 127;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 135. A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 147, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 149, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 151; and
An antibody specific for IGSF1 comprising a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 155, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 157, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 159 or fragments thereof. According to clause 17,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 145;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 153. A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 165, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 167, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 169; and
An antibody specific for IGSF1 comprising a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 173, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 175, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 177 or fragments thereof. According to clause 19,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 163;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 171. A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 183, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 185, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 187; and
An antibody specific for IGSF1 comprising a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 191, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 193, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 195 or fragments thereof. According to clause 21,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 181;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 189. A heavy chain variable region comprising a heavy chain CDR1 represented by the amino acid sequence of SEQ ID NO: 219, a heavy chain CDR2 represented by the amino acid sequence of SEQ ID NO: 221, and a heavy chain CDR3 represented by the amino acid sequence of SEQ ID NO: 223; and
An antibody specific for IGSF1 comprising a light chain variable region comprising a light chain CDR1 represented by the amino acid sequence of SEQ ID NO: 227, a light chain CDR2 represented by the amino acid sequence of SEQ ID NO: 229, and a light chain CDR3 represented by the amino acid sequence of SEQ ID NO: 231 or fragments thereof. According to clause 23,
The heavy chain variable region consists of the amino acid sequence of SEQ ID NO: 217;
An antibody or fragment thereof specific to IGSF1, wherein the light chain variable region consists of the amino acid sequence of SEQ ID NO: 225. According to any one of claims 1 to 24,
The antibody is an antibody or fragment thereof that specifically binds to the C-terminus of IGSF1. A pharmaceutical composition for preventing or treating cancer comprising an antibody specific for IGSF1 or a fragment thereof according to any one of claims 1 to 24 as an active ingredient. According to clause 26,
A pharmaceutical composition for preventing or treating cancer, wherein the cancer overexpresses IGSF1. According to clause 26,
The cancer consists of stomach cancer, liver cancer, lung cancer, colon cancer, breast cancer, prostate cancer, ovarian cancer, pancreas cancer, cervical cancer, thyroid cancer, laryngeal cancer, acute myeloid leukemia, brain tumor, neuroblastoma, retinoblastoma, head and neck cancer, salivary gland cancer, and lymphoma. A pharmaceutical composition for preventing or treating cancer, which is selected from the group.