KR102008960B1 - Monoclonal IgM type antibody specific binding odontoblasts surface and uses thereof - Google Patents

Abstract

The present invention relates to an IgM type monoclonal antibody that specifically binds to the surface of differentiated odontoblasts differentiated from pulp stem cells, and to a composition and method for screening odontoblast differentiation, odontoblast separation, and odontoblast differentiation promoting substance using the same. When using an IgM monoclonal antibody that specifically binds to the odontoblast of the present invention, it is possible to effectively isolate and purify an oblast that can be useful for tissue regeneration and differentiation. It can also be usefully used for the screening of substances that effectively promote differentiation into odontoblasts.

Description

 Monoclonal IgM type antibody specific binding odontoblasts surface and uses else}

The present invention relates to an IgM type monoclonal antibody that specifically binds to the surface of differentiated odontoblasts differentiated from pulp stem cells, and to a composition and method for screening odontoblast differentiation, odontoblast separation, and odontoblast differentiation promoting substance using the same.

Human dental pulp stem cells (hDPSCs) can be obtained from the pulp tissue inside the tooth. The pulp stem cells are multipotent cells such as mesenchymal stem cells (MSCs), and may be differentiated into bone tissue, blood vessels, pulp connective tissue, and nerves in addition to dentin forming teeth.

In teeth, dentin is produced through odontogenesis in ivory progenitor cells. Dentin is one of the highly calcified hard tissues that together make up the tooth, with enamel and chalk. Dentin is formed by inducing calcification of the surrounding substrate by signal molecules and proteins favored by precursor cells called dentin blasts. However, since damage to these tissues due to tooth decay or trauma is very difficult to regenerate, the current dental treatment is based on filling the teeth with a dental material having properties similar to that of dental hard tissue. Therefore, there is a need for research on optimal differentiation conditions for obtaining ivory progenitor cells from pulp stem cells that can be specifically differentiated into dentin.

The present induction process for inducing differentiation from pulp stem cells to ivory progenitor cells has suggested that there are a number of possible cytokines involved in the TGF-β family, but no clear mechanism is known. . For this reason, current clinical and preclinical experiments use only one factor, BMP2, which is known as a representative bone differentiation promoting factor for regeneration of damaged teeth and surrounding tissues.

BMPs belong to the TGF-β family and are known to play an important role in pulp regeneration. In addition to BMP, the TGF-β family includes FGF-2 or TGFβ-1, and it is known that they are involved in tooth and bone regeneration, but major differentiation factors and efficient differentiation conditions have not yet been established. That is, the main differentiation factor and effective differentiation conditions for inducing primary cultured human pulp stem cells from dendritic tissue in human teeth into dentin progenitor cells that can efficiently differentiate into dentin have not yet been established. Therefore, there is a need for research for efficient differentiation from pulp stem cells to dentin progenitor cells that can differentiate into dentin.

In addition, even when effectively differentiated from the pulp stem cells to the odontoblasts has been difficult to separate and use it. At present, the oocytes have been identified as specific markers of 2-3 kinds of monobacterium specific to the cytoplasm or extracellular matrix. It is true. Therefore, there is a need for research on cell surface expressing antigens that can effectively separate and purify oocytes, and furthermore, there is an urgent need for a study for isolating odontoblasts using the same.

The inventors of the present invention, while continuing to research to effectively separate and purify the oocytes, confirmed that the antibody specifically binds to the surface of the oocytes, and confirmed that the oocytes could be effectively separated and purified, thereby completing the present invention. .

Accordingly, it is an object of the present invention to provide a total of 15 types of oocyte-specific IgM monoclonal antibodies and compositions, kits and methods for identifying differentiated odontoblasts, odontoblasts using the same.

It is still another object of the present invention to provide a composition, kit and method for screening differentiation promoting substances that promote differentiation from undifferentiated pulp stem cells to odontoblasts.

In order to achieve the above object, the present invention provides a total of 15 types of oblast-specific IgM monoclonal antibody.

The present invention also provides a hybridoma cell line producing the 15 kinds of oblast-specific IgM monoclonal antibodies.

In another aspect, the present invention provides a composition and kit for identifying differentiated odontoblasts comprising the 15 oocyte-specific IgM monoclonal antibodies.

In another aspect, the present invention comprises the steps of treating the sample 15 kinds of oblast-specific IgM monoclonal antibody to a sample; It provides a method for identifying differentiated oblast cells comprising a.

In another aspect, the present invention provides a composition and kit for separating odontoblasts comprising the 15 kinds of oocyte-specific IgM monoclonal antibodies.

In addition, the present invention comprises the steps of: a) treating the 15 types of oblast-specific IgM monoclonal antibody to a sample of monoclonal antibody; And b) separating the antibody bound to the odontoblast; It provides a method for separating odontoblasts comprising a.

In another aspect, the present invention provides a composition and kit for screening differentiation promoting substance to promote differentiation of undifferentiated pulp stem cells into odontoblasts, including the 15 oocyte-specific IgM monoclonal antibodies.

In addition, the present invention comprises the steps of: a) treating the 15 different oblast-specific IgM monoclonal antibodies to undifferentiated pulp stem cells; b) treating the candidate with undifferentiated pulp stem cells; And c) treating the 15 IgM monoclonal antibodies to a sample to compare the binding reaction with step a); It provides a method of screening a material for differentiating undifferentiated pulp stem cells comprising oocytes.

When using an IgM monoclonal antibody that specifically binds to the surface of the odontoblast of the present invention, it is possible to effectively isolate and purify an oblast that can be usefully used for tissue regeneration and differentiation, and the IgM monoclonal antibody is a pulp stem cell It can be usefully used for screening of substances that effectively promote differentiation into odontoblasts.

1 is a diagram showing the result of confirming the difference in marker expression in the differentiation of the oocytes and hDPCs differentiated by the treatment of rhBMP2 and rhBMP4.
Figure 2 is a diagram briefly showing a method for producing an oblast specific antibody according to the present invention.
Figure 3 is a diagram showing the flow cytometry results for confirming that 15 IgM type antibodies bind to the surface of the odontoblast compared to human pulp stem cells (hDPSC).
4 is a diagram showing sequence information of an oblast-specific IgM type antibody.

The present invention provides an oblast-specific IgM monoclonal antibody.

Since the IgM monoclonal antibody according to the present invention can specifically bind to the differentiated odontoblasts from human pulp stem cells, it can be usefully used to isolate and purify the odontoblasts.

Hereinafter, the present invention will be described in detail.

The present invention provides a) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 1, a light chain CDR2 represented by SEQ ID NO: 2, a light chain CDR3 represented by SEQ ID NO: 3, a heavy chain CDR1 represented by SEQ ID NO: 4, SEQ ID NO: 5 An oblast-specific OD7 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 represented by SEQ ID NO: 6 and a heavy chain CDR3 represented by SEQ ID NO: 6;

b) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 7, a light chain CDR2 represented by SEQ ID NO: 8, a light chain CDR3 represented by SEQ ID NO: 9, a heavy chain CDR1 represented by SEQ ID NO: 10, represented by SEQ ID NO: 11 An oblast-specific OD111A IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 12;

c) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 13, a light chain CDR2 represented by SEQ ID NO: 14, a light chain CDR3 represented by SEQ ID NO: 15, a heavy chain CDR1 represented by SEQ ID NO: 16, represented by SEQ ID NO: 17 An oblast-specific OD169B IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 18;

d) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 19, a light chain CDR2 represented by SEQ ID NO: 20, a light chain CDR3 represented by SEQ ID NO: 21, a heavy chain CDR1 represented by SEQ ID NO: 22, represented by SEQ ID NO: 23 An oblast-specific OD184 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 24;

e) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 25, a light chain CDR2 represented by SEQ ID NO: 26, a light chain CDR3 represented by SEQ ID NO: 27, a heavy chain CDR1 represented by SEQ ID NO: 28, represented by SEQ ID NO: 29 An oblast-specific OD185 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 30;

f) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 31, a light chain CDR2 represented by SEQ ID NO: 32, a light chain CDR3 represented by SEQ ID NO: 33, a heavy chain CDR1 represented by SEQ ID NO: 34, represented by SEQ ID NO: 35 An oblast-specific OD196 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 36;

g) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 37, a light chain CDR2 represented by SEQ ID NO: 38, a light chain CDR3 represented by SEQ ID NO: 39, a heavy chain CDR1 represented by SEQ ID NO: 40, represented by SEQ ID NO: 41 An oblast-specific OD210A IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 42;

h) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 43, a light chain CDR2 represented by SEQ ID NO: 44, a light chain CDR3 represented by SEQ ID NO: 45, a heavy chain CDR1 represented by SEQ ID NO 46, represented by SEQ ID NO 47 An oblast-specific OD225 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 48;

i) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 49, a light chain CDR2 represented by SEQ ID NO: 50, a light chain CDR3 represented by SEQ ID NO: 51, a heavy chain CDR1 represented by SEQ ID NO: 52, represented by SEQ ID NO: 53 An oblast-specific OD234 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 54;

j) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 55, a light chain CDR2 represented by SEQ ID NO: 56, a light chain CDR3 represented by SEQ ID NO: 57, a heavy chain CDR1 represented by SEQ ID NO: 58, represented by SEQ ID NO: 59 An oblast-specific OD241 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 60;

k) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 61, a light chain CDR2 represented by SEQ ID NO: 62, a light chain CDR3 represented by SEQ ID NO: 63, a heavy chain CDR1 represented by SEQ ID NO: 64, represented by SEQ ID NO: 65; An oblast-specific OD244 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 66;

l) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 67, a light chain CDR2 represented by SEQ ID NO: 68, a light chain CDR3 represented by SEQ ID NO: 69, a heavy chain CDR1 represented by SEQ ID NO: 70, represented by SEQ ID NO: 71; An oblast-specific OD270 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 72;

m) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 73, a light chain CDR2 represented by SEQ ID NO: 74, a light chain CDR3 represented by SEQ ID NO: 75, a heavy chain CDR1 represented by SEQ ID NO: 76, represented by SEQ ID NO: 77 An oblast-specific OD296 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 78;

n) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 79, a light chain CDR2 represented by SEQ ID NO: 80, a light chain CDR3 represented by SEQ ID NO: 81, a heavy chain CDR1 represented by SEQ ID NO: 82, represented by SEQ ID NO: 83 An oblast-specific OD298 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 84; And

o) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 85, a light chain CDR2 represented by SEQ ID NO: 86, a light chain CDR3 represented by SEQ ID NO: 87, a heavy chain CDR1 represented by SEQ ID NO: 88, represented by SEQ ID NO: 89 An oblast-specific OD340 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 90; Provided are one oblast-specific IgM monoclonal antibody selected from the group consisting of:

In the present invention, "odontoblasts" refer to columnar cells that form a cell layer on the periphery of the pulp with cells differentiated from pulp progenitor cells. The odontoblasts function directly to the dentin, the chief component of the tooth, which is itself a component of the pulp tissue inside the dentin, arranged in the pulp chamber inside the tooth.

In the present invention, the pulp stem cell (dental pulp stem cell) is a kind of mesenchymal stem cells of the dental origin (dental origin), the mesenchymal mesenchymal stem cells are 'partial (stem) stem cells affected by the epithelial epithelial cells, , Stem cells distributed in the pulp and surrounding tissue of the tooth with mesodermal origin. For example, dental pulp stem cells (DPSC), stem cells from exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSC), root papillary stem cells (stem) cells from the apical papilla (SCAP), and dental follicle precursor cells (DFPC).

In the present invention, the pulp stem cell may be a cell derived from an animal, preferably a mammal, more preferably a human.

The pulp stem cells of the present invention may be autologous, allogenic, xenogenic cells.

The pulp stem cells are present in the inner pulp and the tissues around the teeth, and the process of isolating and culturing them is well known in the art.

"The odontospecific IgM monoclonal antibody" of the present invention is an antibody that binds to factors expressing only on the surface of the odontoblast differentiated from pulp stem cells, and includes light and heavy chain variable regions as defined above. It means an antibody to be.

The antibody of the present invention can be obtained by performing decoy immunization using differentiation-induced oocytes as an immunogen, and obtaining monoclonal antibodies against molecules expressed only on the surface of the differentiated odontoblasts through the bait immunization method. Can be.

The present invention provides a total of 15 IgM monoclonal antibodies obtained through the above method, which in the present invention, respectively, OD7, OD111A, OD169B, OD184, OD185, OD196, OD210A, OD225, OD234, OD241, OD244, It is named OD270, OD296, OD298 and OD340.

In the present invention, the IgM monoclonal antibody comprises the following light and heavy chain variable regions.

OD7 IgM antibody is a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 1, a light chain CDR2 represented by SEQ ID NO: 2, a light chain CDR3 represented by SEQ ID NO: 3, a heavy chain CDR1 represented by SEQ ID NO: 4, SEQ ID NO: It may include a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 6, preferably comprising a light chain variable region represented by SEQ ID NO: 91 and a heavy chain variable region represented by SEQ ID NO: 92 It may be characterized by.

The light chain variable region of the OD7 IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 121, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 122.

OD111A IgM antibody is a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 7, a light chain CDR2 represented by SEQ ID NO: 8, a light chain CDR3 represented by SEQ ID NO: 9, a heavy chain CDR1 represented by SEQ ID NO: 10, SEQ ID NO: 11 It may include a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 12, preferably comprising a light chain variable region represented by SEQ ID NO: 93 and a heavy chain variable region represented by SEQ ID NO: 94 It may be characterized by.

The light chain variable region of the OD111A IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 123, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 124.

OD169B IgM antibody is a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 13, a light chain CDR2 represented by SEQ ID NO: 14, a light chain CDR3 represented by SEQ ID NO: 15, a heavy chain CDR1 represented by SEQ ID NO: 16, SEQ ID NO: 17 It may include a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 18, preferably comprising a light chain variable region represented by SEQ ID NO: 95 and a heavy chain variable region represented by SEQ ID NO: 96 It may be characterized by.

The light chain variable region of the OD169B IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 125, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 126.

OD184 IgM antibody is a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 19, a light chain CDR2 represented by SEQ ID NO: 20, a light chain CDR3 represented by SEQ ID NO: 21, a heavy chain CDR1 represented by SEQ ID NO: 22, SEQ ID NO: 23 It may include a heavy chain variable region comprising a heavy chain CDR2 represented and a heavy chain CDR3 represented by SEQ ID NO: 24, preferably comprising a light chain variable region represented by SEQ ID NO: 97 and a heavy chain variable region represented by SEQ ID NO: 98 It may be characterized by.

The light chain variable region of the OD184 IgM antibody may be encoded by a nucleotide sequence represented by SEQ ID NO: 127, and the heavy chain variable region may be encoded by a nucleotide sequence represented by SEQ ID NO: 128.

OD185 IgM antibody is a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 25, a light chain CDR2 represented by SEQ ID NO: 26, a light chain CDR3 represented by SEQ ID NO: 27, a heavy chain CDR1 represented by SEQ ID NO: 28, SEQ ID NO: 29 It may include a heavy chain variable region comprising a heavy chain CDR2 is represented and a heavy chain CDR3 represented by SEQ ID NO: 30, preferably comprising a light chain variable region represented by SEQ ID NO: 99 and a heavy chain variable region represented by SEQ ID NO: 100 It may be characterized by.

The light chain variable region of the OD185 IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 129, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 130.

OD196 IgM antibody is a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 31, a light chain CDR2 represented by SEQ ID NO: 32, a light chain CDR3 represented by SEQ ID NO: 33, a heavy chain CDR1 represented by SEQ ID NO: 34, SEQ ID NO: 35 It may include a heavy chain variable region comprising a heavy chain CDR2 is represented and a heavy chain CDR3 represented by SEQ ID NO: 36, preferably comprising a light chain variable region represented by SEQ ID NO: 101 and a heavy chain variable region represented by SEQ ID NO: 102 It may be characterized by.

The light chain variable region of the OD196 IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 131, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 132.

OD210A IgM antibody is a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 37, a light chain CDR2 represented by SEQ ID NO: 38, a light chain CDR3 represented by SEQ ID NO: 39, a heavy chain CDR1 represented by SEQ ID NO: 40, SEQ ID NO: 41 It may include a heavy chain variable region comprising a heavy chain CDR2 represented and a heavy chain CDR3 represented by SEQ ID NO: 42, preferably comprising a light chain variable region represented by SEQ ID NO: 103 and a heavy chain variable region represented by SEQ ID NO: 104 It may be characterized by.

The light chain variable region of the OD210A IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 133, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 134.

The OD225 IgM antibody comprises a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 43, a light chain CDR2 represented by SEQ ID NO: 44, a light chain CDR3 represented by SEQ ID NO: 45, a heavy chain CDR1 represented by SEQ ID NO 46, SEQ ID NO 47 It may include a heavy chain variable region comprising a heavy chain CDR2 is represented and a heavy chain CDR3 represented by SEQ ID NO: 48, preferably comprising a light chain variable region represented by SEQ ID NO: 105 and a heavy chain variable region represented by SEQ ID NO: 106 It may be characterized by.

The light chain variable region of the OD225 IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 135, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 136.

OD234 IgM antibody is a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 49, a light chain CDR2 represented by SEQ ID NO: 50, a light chain CDR3 represented by SEQ ID NO: 51, a heavy chain CDR1 represented by SEQ ID NO: 52, SEQ ID NO: 53 It may include a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 54, preferably comprising a light chain variable region represented by SEQ ID NO: 107 and a heavy chain variable region represented by SEQ ID NO: 108 It may be characterized by.

The light chain variable region of the OD234 IgM antibody may be encoded by a nucleotide sequence represented by SEQ ID NO: 137, and the heavy chain variable region may be encoded by a nucleotide sequence represented by SEQ ID NO: 138.

 OD241 IgM antibody is a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 55, a light chain CDR2 represented by SEQ ID NO: 56, a light chain CDR3 represented by SEQ ID NO: 57, a heavy chain CDR1 represented by SEQ ID NO: 58, SEQ ID NO: 59 It may include a heavy chain variable region comprising a heavy chain CDR2 is represented and a heavy chain CDR3 represented by SEQ ID NO: 60, preferably comprising a light chain variable region represented by SEQ ID NO: 109 and a heavy chain variable region represented by SEQ ID NO: 110 It may be characterized by.

The light chain variable region of the OD241 IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 139, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 140.

The OD244 IgM antibody comprises a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 61, a light chain CDR2 represented by SEQ ID NO: 62, a light chain CDR3 represented by SEQ ID NO: 63, a heavy chain CDR1 represented by SEQ ID NO: 64, SEQ ID NO: 65; It may include a heavy chain variable region comprising a heavy chain CDR2 represented and a heavy chain CDR3 represented by SEQ ID NO: 66, preferably comprising a light chain variable region represented by SEQ ID NO: 111 and a heavy chain variable region represented by SEQ ID NO: 112 It may be characterized by.

The light chain variable region of the OD244 IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 141, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 142.

OD270 IgM antibody is a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 67, a light chain CDR2 represented by SEQ ID NO: 68, a light chain CDR3 represented by SEQ ID NO: 69, a heavy chain CDR1 represented by SEQ ID NO: 70, SEQ ID 71 It may include a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 72, preferably comprising a light chain variable region represented by SEQ ID NO: 113 and a heavy chain variable region represented by SEQ ID NO: 114 It may be characterized by.

The light chain variable region of the OD270 IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 143, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 144.

OD296 IgM antibody is a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 73, a light chain CDR2 represented by SEQ ID NO: 74, a light chain CDR3 represented by SEQ ID NO: 75, a heavy chain CDR1 represented by SEQ ID NO: 76, SEQ ID NO: 77 A heavy chain variable region comprising a heavy chain CDR2 to be displayed and a heavy chain CDR3 represented by SEQ ID NO: 78, preferably comprising a light chain variable region represented by SEQ ID NO: 115 and a heavy chain variable region represented by SEQ ID NO: 116 It may be characterized by.

The light chain variable region of the OD296 IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 145, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 146.

OD298 IgM antibody comprises a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 79, a light chain CDR2 represented by SEQ ID NO: 80, a light chain CDR3 represented by SEQ ID NO: 81, a heavy chain CDR1 represented by SEQ ID NO: 82, SEQ ID NO: 83; It may include a heavy chain variable region comprising a heavy chain CDR2 is represented and a heavy chain CDR3 represented by SEQ ID NO: 84, preferably comprising a light chain variable region represented by SEQ ID NO: 117 and a heavy chain variable region represented by SEQ ID NO: 118 It may be characterized by.

The light chain variable region of the OD298 IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 147, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 148.

The OD340 IgM antibody comprises a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 85, a light chain CDR2 represented by SEQ ID NO: 86, a light chain CDR3 represented by SEQ ID NO: 87, a heavy chain CDR1 represented by SEQ ID NO: 88, SEQ ID NO: 89 It may include a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 90, preferably comprising a light chain variable region represented by SEQ ID NO: 119 and a heavy chain variable region represented by SEQ ID NO: 120 It may be characterized by.

The light chain variable region of the OD340 IgM antibody may be encoded by the nucleotide sequence represented by SEQ ID NO: 149, and the heavy chain variable region may be encoded by the nucleotide sequence represented by SEQ ID NO: 150.

The sequences of the antibodies of the invention may be altered, such as conservative substitutions, in accordance with the technical common sense of one of ordinary skill in the art as long as the object of the invention can be achieved as an odontospecific binding. And all polypeptides having a sequence homology of from 99% to 99%, preferably from 85% to 99%, more preferably from 90% to 99%.

The term “conservative substitutions” refers to the replacement of one class of amino acids with another amino acid of the same class. Conservative substitutions do not alter the structure or function of the polypeptide or both. Classes of amino acids for the purpose of conservative substitutions are hydrophobic (eg Met, Ala, Val, Leu), neutral hydrophilic (eg Cys, Ser, Thr), acidic (eg Asp, Glu) , Basics (eg Asn, Gln, His, Lys, Arg), conformational disruptors (eg Gly, Pro) and aromatics (eg Trp, Tyr, Phe) .

In addition, the IgM monoclonal antibody of the present invention encodes each CDR region, light chain and heavy chain variable region represented by SEQ ID NOS: 1 to 120, as long as the object of the antibody of the present invention, which is differentiated oocyte surface specific binding, can be achieved. It may be encoded by a variety of sequences, and particularly preferably may be encoded by a nucleotide sequence represented by each SEQ ID NO: 121 to 150, but is not limited thereto, 80 to 99 that can encode the equivalent polypeptide It may be encoded by a nucleotide sequence having% homology, 90 to 99% homology, 95 to 99% homology.

The IgM monoclonal antibody of the present invention may be characterized in that it specifically binds to differentiated oocytes, for example, from dendritic stem cells by treatment of bone morphogenetic protein 2 (BMP2) and bone morphogenetic protein 4 (BMP4). Can specifically bind to cells differentiated into

Monoclonal antibodies provided in the present invention can be prepared by methods known in the art. As an example, the peptide may be prepared by a chemical peptide synthesis method, the gene encoding the monoclonal antibody may be amplified by PCR (polymerase chain reaction) or synthesized by a known method, and then cloned into an expression vector for expression. It can also be prepared using a hybridoma cell line derived from lymphocytes obtained by injecting an immunogen of said monoclonal antibody into an animal, and as another example, inoculating an animal with an immunogen into differentiated odontoblasts and using lymphocytes obtained from said animal It can be prepared using a hybridoma cell line prepared.

Thus, the present invention provides hybridoma cell lines that produce IgM monoclonal antibodies.

The hybridoma cell line is a cell made by artificially fusion of two different kinds of cells, and two or more allogeneic or heterologous cells are fused using a substance causing a cell fusion, such as polyethylene glycol, or some kind of virus, respectively. A cell or cell line incorporating different functions of another cell into one cell. In particular, hybrid cells in which myeloma cells and B cells, which are precursor cells of antibody-producing cells, are fused among myeloma cells and lymphocytes contained in the spleen or lymph nodes, are widely used in research and clinical practice. In addition, T cells producing lymphokines (physiologically active substances) and hybrid horses, which are tumor cells thereof, have been put to practical use. The hybridoma cell of the present invention may be a cell in which lymphocytes and myeloma cells are immunized with the oocytes, and the hybridoma cell line capable of producing an IgM monoclonal antibody that specifically binds to the differentiated oocytes. It may include without limitation.

The present invention also provides a composition and kit for identifying differentiated odontoblasts comprising the IgM monoclonal antibody of the present invention.

The IgM monoclonal antibody of the present invention is an antibody that specifically binds to odontoblasts, preferably odontoblasts differentiated from pulp stem cells, and can more effectively bind to the surface of the odontoblasts compared to pulp stem cells before differentiation. Therefore, using the IgM monoclonal antibody of the present invention can effectively identify and determine whether the progenitor cells in the sample has been differentiated into odontoblasts.

In order to confirm and discriminate such an antibody, the antibody of the present invention may be labeled with a distinguishable label, and the label may be bound to the monoclonal antibody to be used for distinguishing or separating differentiated oocytes expressing a surface antigen of interest. As far as possible, it is not particularly limited. Such as ligands, beads, radionuclides, enzymes, substrates, cofactors, inhibitors, fluorescers, chemiluminescent materials, magnetic particles, hapten, dyes and the like, and other examples include biotin, avidin, Ligands such as streptoavidine; Enzymes such as luciferase, peroxidase and beta galactosidase; Fluorescein, 6-carboxyfluorescein, nucleosacro-6-carboxyfluorescein, tetrachloro-6-carboxyfluorescein, VIC, JOE, 5- (2'-aminoethyl) amino naphthalene-1 -Fluorescent materials such as sulfonic acid, coumarin and derivatives thereof, cyanine-5, lucifer yellow, texas red, tetramethyltamine, yakima yellow, cal fluored red 610, coumarin, derivatives thereof, and the like, without limitation, may be included in the labeling material. Can be.

In another aspect, the present invention comprises the steps of treating the sample with the IgM monoclonal antibody; It provides a method for identifying differentiated oblast cells comprising a.

According to the method of the present invention, it is easy to check whether pulp stem cells are differentiated into odontoblasts by using the property of the IgM monoclonal antibody of the present invention to bind to specific antigens expressed on the surface of odontoblasts.

For example, the IgM monoclonal antibody of the present invention can be labeled for detection, and when the pulp stem cells present in the sample are induced to differentiate into odontoblasts, the oocytes differentiated through label detection of the IgM monoclonal antibody bound to the odontoblasts. You can check. In this case the method of the present invention comprises the steps of: a) treating the sample with IgM monoclonal antibody; And b) detecting the IgM monoclonal antibody bound to the cells in the sample; It may include.

If differentiation is detected in the differentiation-induced sample by comparing the bound IgM monoclonal antibody detected in the sample containing the cells, such as pulp stem cells, with the bound IgM monoclonal antibody detected in the differentiation-induced sample, prior to differentiation When the content of the IgM monoclonal antibody increased, pulp stem cells can be differentiated into odontoblasts, it can be seen that the differentiated oocytes present in the sample.

In another aspect, the present invention provides a composition and kit for separating odontoblasts comprising IgM monoclonal antibody.

Since the IgM monoclonal antibody of the present invention can specifically detect differentiated oocytes, the IgM monoclonal antibody can be effectively separated from a sample, such as a sample mixed with undifferentiated pulp stem cells.

In another aspect, the present invention comprises the steps of: a) treating the sample with the IgM monoclonal antibody of the present invention; And b) separating the antibody bound to the odontoblast; It provides a method for separating odontoblasts comprising a.

Separation of the antibody bound to the odontoblast may be carried out using a method commonly used in the art. For example, flow cytometry, immunoprecipitation, autoactive cell separation, chromatography, etc. may be used. As another example, flow cytometry using a fluorescently labeled composition, immunoprecipitation using a composition comprising an agent bound to gold particles, magnetic separation using a composition bound to magnetic beads, beads bound to the agent Chromatography using a column packed with the like may be used.

The present invention also provides a composition and kit for screening differentiation promoting substances for promoting differentiation of undifferentiated pulp stem cells into odontoblasts, comprising the IgM monoclonal antibody of the present invention.

Since the IgM monoclonal antibody of the present invention can specifically bind to differentiated odontoblasts, the IgM monoclonal antibody can be used to compare the degree of binding before the differentiation candidate candidate treatment and the degree of binding after the differentiation candidate candidate treatment. It can be used for the screening of differentiation promoting substances that promote differentiation into odontoblasts.

Accordingly, the present invention comprises the steps of: a) treating the IgM monoclonal antibody of the present invention to undifferentiated pulp stem cells; b) treating the candidate with undifferentiated pulp stem cells; And c) treating the sample with the IgM monoclonal antibody of the present invention to compare the binding reaction with step a); It provides a method of screening a material for differentiating undifferentiated pulp stem cells comprising oocytes.

The kit used in the present invention may be an immunofluorescence kit including a substrate on which a formulation of the composition is immobilized and a secondary antibody specific to the IgM monoclonal antibody and to which a fluorescent substance is bound. As another example, the kit may be a chromatography kit comprising beads to which the formulation of the composition is bound, a column into which the beads may be filled, and a buffer for development. As another example, the kit may be a MACS kit including biotin combined with a formulation of the composition, streptavidin bound with magnetic beads, and a magnetic generator.

Hereinafter, the present invention will be described in detail by way of examples. However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited by the following examples.

Example  One. Dentin  Obtaining Specific Monoclonal Antibodies

For primary culture of human dental pulp stem cells (hDPCs), wisdom teeth received from adult patients (ages 20-27) were reviewed by IRB of the Dankook University Dental Hospital. Human pulp tissue was obtained by cutting the tooth and extracting the tissue contained therein, and then finely chopped, 3 mg / ml collagenase type I (Millipore), 4 mg / ml dispase (Sigma) -Aldrich) was treated as a single cell at 37 ° C. for 1 hour (Choi et al., 2015; Min et al., 2011). Isolated single cells were incubated in α-MEM (Hyclone) with 20% fetal bovine serum (FBS, Hyclone) and antibiotic (Lonza) in 37 ℃, 5% CO ₂ incubator. In order to differentiate human pulp-derived stem cells into odontoblasts, hDPCs cultured in α-MEM with 10% FBS were simultaneously treated with 100ng / ml of rhBMP2 (Sino Biological) and 10ng / ml of rhBMP4 (Prospec). Further incubation for days. hDPCs were effectively differentiated into odontoblasts by treatment with rhBMP2 and rhBMP4. In addition, markers showing significantly higher expression levels were identified in the differentiating odontoblasts treated with rhBMP2 and rhBMP4 compared to hDPCs, and the results are shown in FIG. 1.

As shown in FIG. 1, in odontoblasts treated with 100 ng / ml of rBMP2 and 10 ng / ml of rBMP4, Runx2, osteopontin, osterix, BSP, DMP1, DSPP compared to human pulp cells (hDPCs) It was confirmed that the expression of the gene is significantly higher.

In order to obtain monoclonal antibodies against molecules expressed only on the surface of differentiated odontoblasts, decoy immunization was performed using the obtained odontoblasts as an immunogen. Negative hDPCs were used as negative control cells. More specifically, cells cultured in an incubator were separated using Enzyme Free Cell Dissociation Solution (Millipore), and then 5 × 10 ⁵ cells were suspended in 30 μl of PBS to the rear of 10 6-week-old Balb / c mice (DBL). Injections were made to the soles of the feet. Referring to the previously reported method (Yin et al., 1997), first, the negative control hDPCs were injected into the right hind paw at 0, 3, 6, 9, 12, 15, 18, 21, 24 days for immune response. Induction of differentiation-induced odontoblasts was injected on the left hind paw at 3, 6, 9, 12, 15, 18, 21 and 24 days to induce an immune response. On day 24, lymph nodes were extracted from the left hamstring and the extracted lymphocytes were allowed to fusion with myeloma cells (ATCC) (lymphocytes immunized with oblasts; 8 × 10 ⁷ cells / 10). The fused hybridoma cells were plated with DMEM medium supplemented with 20% FBS (Hyclone), HFCS (Roche) and HAT (Sigma-Aldrich) in 96-well plates (Kohler and Milstein, 1975). Hybridoma culture medium was collected and ELISA and flow cytometry were used to verify antibody production and binding to odontoblasts. The process for obtaining an antibody that binds to a factor specifically expressing only the differentiation-induced odontoblast surface using bait immunoassay is briefly shown in FIG.

Example  2. Monoclonal Antibody Purification

The monoclonal antibody prepared in Example 1 was purified using column chromatography using a culture medium in which hybridomas were cultured. Protein L Agarose (Thermo) column was used to purify IgM type monoclonal antibody. Agarose was washed with PBS after flowing the medium, and bound IgM monoclonal antibody was eluted with 100 mM glycine buffer (pH 2.8) and immediately neutralized by addition of 1 M Tris-HCl buffer (pH 9.0). After dialysis with PBS, the antibody concentration was determined.

2.1 Monoclonal Antibodies isotyping  analysis

To determine the immune isotype of the purified monoclonal antibody, first coated with 96-well plate anti-mouse IgM1, IgM2a, IgM2b, IgM3, IgM, IgA, Igκ, Igλ, and then with PBS containing 10% FBS. Blocked. After adding each hybridoma-grown medium or purified monoclonal antibody, the mixture was allowed to react for a predetermined time, followed by reaction with a secondary antibody. As a secondary antibody, an antibody conjugated with horseradish peroxidase was used, and the reaction was confirmed at 450 nm wavelength. The results are shown in Table 1.

TABLE 1

As shown in Table 1, finally, 15 kinds of IgM type antibodies such as OD7, OD111A, OD169B, OD184, OD185, OD196, OD210A, OD225, OD234, OD241, OD244, OD270, OD296, OD298 and OD340 were obtained. It was.

2.2 Flow cell  Antibody Binding Affinity Measurement by Assay

Flow cytometry was performed for cell-antibody responses to confirm whether the antibody prepared in Example 1 binds better to the odontoblasts on the surface of hDPCs and odontoblasts. More specifically, Enzyme Free Cell Dissociation Solution (Millipore) was added to incubate for 10 minutes and then removed from the culture dish and collected. The hDPSCs and the odontoblasts were resuspended in PBS with 1x BSA (GeneDEPOT), separated by about 3 × 10 ⁴ , and then reacted on ice for 1 hour by the addition of purified monoclonal antibody or hybridoma culture medium. After washing, FITC-conjugated anti-mouse IgM (1: 100, Santa Cruz) or PE-conjugated anti-mouse IgM (1: 100, Santa Cruz) was added as a secondary antibody and reacted on ice for 1 hour. The binding degree of the antibody bound to the cell surface was analyzed by FACS Calibur ^™ (BD Biosciences), and the antibody binding affinity was quantified using the Cell Quest pro and WinMDI programs, and the results are shown in FIG. 3. As a control group, cells stained using only PE-conjugated anti-mouse IgM were used.

As shown in FIG. 3, all 15 IgM-type antibodies were confirmed to bind to antigens expressed higher in odontoblasts than hDPCs or expressed only in odontoblasts. These results indicate that the 15 monoclonal antibodies can be used to purely separate the oocytes by specifically binding to surface antigens specifically expressed on human odontoblasts.

Example  3. Antibody Sequencing

In order to analyze the gene sequence of the antibody obtained in Example 1, primers for amplifying the variable regions of the heavy and light chains of the antibody were synthesized according to the method of Wang et al., 2000 and the like. The sequence of the primer used is as follows. For other isotypes, primers suitable for this were synthesized.

TABLE 2

^Easy-TM spin to collect the hybridoma cells (~ 1x10 ⁶ cells) to extract total RNA Total RNA Extraction kit (Intron) was used. cDNA was synthesized for 30 minutes at 45 ℃ using Maxime RT-PCR PreMix Kit (Intron), RT-PCR reaction was 94 1 cycle for 5 minutes at ℃, 1 minute at 94 ℃, 1 minute at 45 ℃, 30 cycles for 1 minute at 72 ℃, the final cycle was carried out for 5 minutes at 72 ℃. Heavy DNA fragments were cloned into the pBluescript KS (+) vector and sequenced. The consensus domain of the antibody is Analysis was performed according to Andrew CR Martin's Group database dp.

The CDR region is a site that recognizes and binds a specific antigen, and CDR1 and 2 are found in a variable region (V), and in the case of heavy chain, some V region, diversity region (D), and joining region in CDR3. region, J), and the light chain contains the V and J regions in CDR3. Sequence information of the IgM type antibody confirmed through sequencing is shown in FIG. 4.

In addition, the nucleotide sequences encoding the light and heavy chains of these individual antibodies are shown in SEQ ID NOs: 121-150.

<110> Dankook University Cheonan Campus Industry Academic Cooperation Foundation <120> Monoclonal IgM type antibody specific binding odontoblasts          surface and uses according <130> DANKOOK1-17p <160> 150 <170> KoPatentIn 3.0 <210> 1 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD7 Light chain CDR1 <400> 1 Arg Ala Ser Gln Ser Ile Ser Asn Asn Leu His   1 5 10 <210> 2 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD7 Light chain CDR2 <400> 2 Tyr Ala Ser Gln Ser Ile Ser   1 5 <210> 3 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD7 Light chain CDR3 <400> 3 Gln Gln Ser Asn Ser Trp Pro Leu Thr   1 5 <210> 4 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD7 Heavy chain CDR1 <400> 4 Gly Tyr Ser Phe Thr Ser Tyr Trp Met Asn   1 5 10 <210> 5 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD7 Heavy chain CDR2 <400> 5 Met Ile His Pro Ser Asp Ser Glu Thr Arg Leu Asn Gln Lys Phe Lys   1 5 10 15 Asp     <210> 6 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> OD7 Heavy chain CDR3 <400> 6 Pro Val Val Ala Thr Gly Arg Tyr Tyr Ser Met Asp Tyr   1 5 10 <210> 7 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD111A Light chain CDR1 <400> 7 Arg Ala Ser Glu Asn Ile Tyr Ser Tyr Leu Ala   1 5 10 <210> 8 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD111A Light chain CDR2 <400> 8 Asn Ala Lys Thr Leu Ala Glu   1 5 <210> 9 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD111A Light chain CDR3 <400> 9 Gln His His Tyr Gly Thr Pro Leu Thr   1 5 <210> 10 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD111A Heavy chain CDR1 <400> 10 Gly Tyr Thr Phe Ser Ser Tyr Trp Ile Glu   1 5 10 <210> 11 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD111A Heavy chain CDR2 <400> 11 Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Asn Glu Lys Phe Lys   1 5 10 15 Gly     <210> 12 <211> 14 <212> PRT <213> Artificial Sequence <220> <223> OD111A Heavy chain CDR3 <400> 12 Arg Lys Trp Gly Asn Tyr Val Asn Tyr Tyr Ala Met Asp Tyr   1 5 10 <210> 13 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD169B Light chain CDR1 <400> 13 Ser Ala Ser Ser Ser Val Ser Tyr Met His   1 5 10 <210> 14 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD169B Light chain CDR2 <400> 14 Asp Thr Ser Lys Leu Ala Ser   1 5 <210> 15 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD169B Light chain CDR3 <400> 15 Gln Gln Trp Ser Ser Asn Pro Pro Thr   1 5 <210> 16 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD169B Heavy chain CDR1 <400> 16 Gly Phe Ser Leu Thr Ser Tyr Gly Val Ser   1 5 10 <210> 17 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> OD169B Heavy chain CDR2 <400> 17 Val Ile Trp Gly Asp Gly Ser Thr Asn Tyr His Ser Ala Leu Ile Ser   1 5 10 15 <210> 18 <211> 4 <212> PRT <213> Artificial Sequence <220> <223> OD169B Heavy chain CDR3 <400> 18 Tyr Arg Gly Tyr   One <210> 19 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> OD184 Light chain CDR1 <400> 19 Arg Ser Ser Lys Ser Leu Leu His Ser Asn Gly Ile Thr Tyr Leu Tyr   1 5 10 15 <210> 20 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD184 Light chain CDR2 <400> 20 Gln Met Ser Asn Leu Ala Ser   1 5 <210> 21 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD184 Light chain CDR3 <400> 21 Ala Gln Asn Leu Glu Leu Pro Pro Thr   1 5 <210> 22 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD184 Heavy chain CDR1 <400> 22 Asp Ser Glu Val Phe Pro Ile Ala Tyr Met Ser   1 5 10 <210> 23 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD184 Heavy chain CDR2 <400> 23 Asp Ile Leu Pro Ser Ile Gly Arg Thr Ile Tyr Gly Glu Lys Phe Glu   1 5 10 15 Asp     <210> 24 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> OD184 Heavy chain CDR3 <400> 24 Glu Gly Ser Ser Gly Tyr Gly Ala Trp Phe Ala Tyr   1 5 10 <210> 25 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD185 Light chain CDR1 <400> 25 Lys Ser Ser Gln Ser Leu Leu Asn Ser Gly Asn Gln Lys Asn Tyr Leu   1 5 10 15 Ala     <210> 26 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD185 Light chain CDR2 <400> 26 Gly Ala Ser Thr Arg Glu Ser   1 5 <210> 27 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD185 Light chain CDR3 <400> 27 Gln Asn Asp His Ser Tyr Pro Tyr Thr   1 5 <210> 28 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> OD185 Heavy chain CDR1 <400> 28 Gly Phe Ser Leu Ser Thr Ser Gly Met Gly Val Gly   1 5 10 <210> 29 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> OD185 Heavy chain CDR2 <400> 29 His Ile Trp Trp Asp Asp Asp Lys Arg Tyr Asn Pro Ala Leu Lys Ser   1 5 10 15 <210> 30 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> OD185 Heavy chain CDR3 <400> 30 Ile Glu Asp Ser Leu Leu Pro Leu Gly Phe Ala Tyr   1 5 10 <210> 31 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD196 Light chain CDR1 <400> 31 Lys Ala Ser Gln Asn Val Gly Thr Asn Val Ala   1 5 10 <210> 32 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD196 Light chain CDR2 <400> 32 Ser Ala Ser Tyr Arg Tyr Ser   1 5 <210> 33 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD196 Light chain CDR3 <400> 33 Gln Gln Tyr Asn Ser Tyr Pro Tyr Thr   1 5 <210> 34 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD196 Heavy chain CDR1 <400> 34 Gly Tyr Thr Phe Thr Glu Tyr Thr Met His   1 5 10 <210> 35 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD196 Heavy chain CDR2 <400> 35 Gly Ile Asn Pro Asn Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys   1 5 10 15 Gly     <210> 36 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> OD196 Heavy chain CDR3 <400> 36 Gly Tyr Ala Met Asp Tyr   1 5 <210> 37 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> OD210A Light chain CDR1 <400> 37 Arg Ala Ser Glu Ser Val Asp Asn Tyr Gly Ile Ser Phe Met Asn   1 5 10 15 <210> 38 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD210A Light chain CDR2 <400> 38 Ala Ala Ser Asn Gln Gly Ser   1 5 <210> 39 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD210A Light chain CDR3 <400> 39 Gln Gln Ser Lys Glu Val Pro Arg Thr   1 5 <210> 40 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD210A Heavy chain CDR1 <400> 40 Gly Phe Asp Phe Ser Arg Tyr Trp Met Ser   1 5 10 <210> 41 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD210A Heavy chain CDR2 <400> 41 Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Thr Pro Ser Leu Lys   1 5 10 15 Asp     <210> 42 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD210A Heavy chain CDR3 <400> 42 Arg Gly Ile Tyr Tyr Gly Asn Tyr Cys Asp Tyr   1 5 10 <210> 43 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD225 Light chain CDR1 <400> 43 Lys Ser Ser Gln Ser Leu Leu Asn Ser Gly Asn Gln Lys Asn Tyr Leu   1 5 10 15 Ala     <210> 44 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD225 Light chain CDR2 <400> 44 Gly Ala Ser Thr Arg Glu Ser   1 5 <210> 45 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD225 Light chain CDR3 <400> 45 Gln Asn Asp His Ser Tyr Pro Phe Thr   1 5 <210> 46 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD225 Heavy chain CDR1 <400> 46 Gly Tyr Thr Phe Thr Ser Tyr Trp Met His   1 5 10 <210> 47 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD225 Heavy chain CDR2 <400> 47 Asp Ile Tyr Pro Gly Ser Asp Ser Thr Asn Tyr Asn Glu Lys Phe Lys   1 5 10 15 Ser     <210> 48 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD225 Heavy chain CDR3 <400> 48 Cys Asp Phe Tyr Trp Tyr Phe Asp Val   1 5 <210> 49 <211> 15 <212> PRT <213> Artificial Sequence <220> <223> OD234 Light chain CDR1 <400> 49 Arg Ala Ser Lys Ser Val Ser Thr Ser Gly Tyr Ser Tyr Met His   1 5 10 15 <210> 50 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD234 Light chain CDR2 <400> 50 Leu Val Ser Asn Leu Glu Ser   1 5 <210> 51 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD234 Light chain CDR3 <400> 51 Gln His Ile Arg Glu Leu Thr Arg Ser   1 5 <210> 52 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD234 Heavy chain CDR1 <400> 52 Gly Tyr Ser Phe Thr Gly Tyr Thr Met Asn   1 5 10 <210> 53 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD234 Heavy chain CDR2 <400> 53 Leu Ile Asn Pro Tyr Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys   1 5 10 15 Gly     <210> 54 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD234 Heavy chain CDR3 <400> 54 Val Arg Ala Tyr Tyr Gly Asn Tyr Glu Leu Phe Tyr Trp Tyr Phe Asp   1 5 10 15 Val     <210> 55 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD241 Light chain CDR1 <400> 55 Ile Thr Ser Thr Asp Ile Asp Asp Asp Met Asn   1 5 10 <210> 56 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD241 Light chain CDR2 <400> 56 Glu Gly Asn Thr Leu Arg Pro   1 5 <210> 57 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD241 Light chain CDR3 <400> 57 Leu Gln Ser Asp Asn Met Pro Phe Thr   1 5 <210> 58 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> OD241 Heavy chain CDR1 <400> 58 Gly Phe Ser Leu Ser Thr Ser Gly Met Ser Val Gly   1 5 10 <210> 59 <211> 16 <212> PRT <213> Artificial Sequence <220> <223> OD241 Heavy chain CDR2 <400> 59 His Ile Trp Trp Asn Asp Asp Lys Tyr Tyr Asn Pro Ala Leu Lys Ser   1 5 10 15 <210> 60 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD241 Heavy chain CDR3 <400> 60 Ile Ala Arg Glu Val Arg Arg Tyr Phe Asp Val   1 5 10 <210> 61 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD244 Light chain CDR1 <400> 61 Ser Ala Ser Ser Ser Val Ser Tyr Met Tyr   1 5 10 <210> 62 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD244 Light chain CDR2 <400> 62 Arg Thr Ser Asn Leu Ala Ser   1 5 <210> 63 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD244 Light chain CDR3 <400> 63 Gln Gln Tyr His Ser Tyr Pro Met Tyr Thr   1 5 10 <210> 64 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD244 Heavy chain CDR1 <400> 64 Gly Tyr Thr Phe Thr Ser Tyr Trp Met His   1 5 10 <210> 65 <211> 19 <212> PRT <213> Artificial Sequence <220> <223> OD244 Heavy chain CDR2 <400> 65 Ala Ile Tyr Pro Gly Asn Ser Asp Thr Ser Tyr Asn Gln Lys Phe Lys   1 5 10 15 Gly lys ala             <210> 66 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD244 Heavy chain CDR3 <400> 66 Ser Gly Pro Pro Tyr Trp Tyr Phe Asp Val   1 5 10 <210> 67 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD270 Light chain CDR1 <400> 67 Lys Ala Ser Gln Asp Ile Asn Lys Tyr Ile Ala   1 5 10 <210> 68 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD270 Light chain CDR2 <400> 68 Tyr Thr Ser Thr Leu Gln Pro   1 5 <210> 69 <211> 8 <212> PRT <213> Artificial Sequence <220> <223> OD270 Light chain CDR3 <400> 69 Leu Gln Tyr Asp Asn Leu Trp Thr   1 5 <210> 70 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD270 Heavy chain CDR1 <400> 70 Gly Tyr Ser Phe Thr Ser Tyr Trp Met Asn   1 5 10 <210> 71 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD270 Heavy chain CDR2 <400> 71 Met Ile His Pro Ser Asp Ser Glu Thr Arg Leu Asn Gln Lys Phe Lys   1 5 10 15 Asp     <210> 72 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> OD270 Heavy chain CDR3 <400> 72 Gly Tyr Ala Met Asp Tyr   1 5 <210> 73 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD296 Light chain CDR1 <400> 73 Lys Ser Ser Gln Ser Leu Leu Trp Ser Val Asn Gln Asn Asn Tyr Leu   1 5 10 15 Ser     <210> 74 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD296 Light chain CDR2 <400> 74 Gly Ala Ser Ile Arg Glu Ser   1 5 <210> 75 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD296 Light chain CDR3 <400> 75 Gln His Asn His Gly Ser Phe Leu Pro Leu Thr   1 5 10 <210> 76 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD296 Heavy chain CDR1 <400> 76 Gly Tyr Thr Phe Thr Ser Tyr Val Met His   1 5 10 <210> 77 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD296 Heavy chain CDR2 <400> 77 Tyr Ile Asn Pro Tyr Asn Asp Gly Thr Lys Tyr Asn Glu Lys Phe Lys   1 5 10 15 Gly     <210> 78 <211> 13 <212> PRT <213> Artificial Sequence <220> <223> OD296 Heavy chain CDR3 <400> 78 Arg Glu Lys Tyr Gly Asn Tyr Val Gly Ala Met Asp Tyr   1 5 10 <210> 79 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD298 Light chain CDR1 <400> 79 Arg Ala Ser Gln Ser Ile Gly Thr Ser Ile His   1 5 10 <210> 80 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD298 Light chain CDR2 <400> 80 Tyr Ala Ser Glu Ser Ile Ser   1 5 <210> 81 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD298 Light chain CDR3 <400> 81 Gln Gln Ser Asn Ser Trp Pro Tyr Thr   1 5 <210> 82 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD298 Heavy chain CDR1 <400> 82 Gly Tyr Thr Phe Thr Asp Tyr Ala Met His   1 5 10 <210> 83 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD298 Heavy chain CDR2 <400> 83 Val Ile Ser Thr Tyr Ser Gly Asn Thr Asn Tyr Asn Gln Lys Phe Lys   1 5 10 15 Gly     <210> 84 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD298 Heavy chain CDR3 <400> 84 Glu Ala Ser Gly Leu Cys Pro Phe Asp Tyr   1 5 10 <210> 85 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD340 Light chain CDR1 <400> 85 Arg Ala Ser Gly Asn Ile His Asn Tyr Leu Ala   1 5 10 <210> 86 <211> 7 <212> PRT <213> Artificial Sequence <220> <223> OD340 Light chain CDR2 <400> 86 Asn Ala Lys Thr Leu Ala Asp   1 5 <210> 87 <211> 9 <212> PRT <213> Artificial Sequence <220> <223> OD340 Light chain CDR3 <400> 87 Gln His Phe Trp Ser Thr Pro Leu Thr   1 5 <210> 88 <211> 10 <212> PRT <213> Artificial Sequence <220> <223> OD340 Heavy chain CDR1 <400> 88 Gly Tyr Thr Phe Thr Asp Tyr Asn Met His   1 5 10 <210> 89 <211> 17 <212> PRT <213> Artificial Sequence <220> <223> OD340 Heavy chain CDR2 <400> 89 Tyr Ile Tyr Pro Tyr Asn Gly Gly Thr Gly Tyr Asn Gln Lys Phe Lys   1 5 10 15 Ser     <210> 90 <211> 11 <212> PRT <213> Artificial Sequence <220> <223> OD340 Heavy chain CDR3 <400> 90 Ala Asp Gly Asn His Pro Tyr Tyr Phe Asp Tyr   1 5 10 <210> 91 <211> 107 <212> PRT <213> Artificial Sequence <220> <223> OD7 Light chain <400> 91 Phe Arg Lys Leu Asp Ile Gln Leu Thr Gln Ser Pro Ala Thr Leu Ser   1 5 10 15 Val Thr Pro Gly Asp Ser Val Ser Leu Ser Cys Arg Ala Ser Gln Ser              20 25 30 Ile Ser Asn Asn Leu His Trp Tyr Gln Gln Lys Ser His Glu Ser Pro          35 40 45 Arg Leu Leu Ile Lys Tyr Ala Ser Gln Ser Ile Ser Gly Ile Pro Ser      50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn  65 70 75 80 Ser Val Glu Thr Glu Asp Phe Gly Met Tyr Phe Cys Gln Gln Ser Asn                  85 90 95 Ser Trp Pro Leu Thr Phe Gly Ala Gly Pro Ser             100 105 <210> 92 <211> 120 <212> PRT <213> Artificial Sequence <220> <223> OD7 Heavy chain <400> 92 Phe Arg Lys Phe Glu Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val   1 5 10 15 Arg Pro Gly Ala Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Ser              20 25 30 Phe Thr Ser Tyr Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly          35 40 45 Leu Glu Trp Ile Gly Met Ile His Pro Ser Asp Ser Glu Thr Arg Leu      50 55 60 Asn Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser  65 70 75 80 Ser Thr Ala Tyr Met Gln Leu Ser Ser Pro Thr Ser Glu Asp Ser Ala                  85 90 95 Val Tyr Tyr Cys Ala Arg Pro Val Val Ala Thr Gly Arg Tyr Tyr Ser             100 105 110 Met Asp Tyr Trp Gly Gln Gly Thr         115 120 <210> 93 <211> 116 <212> PRT <213> Artificial Sequence <220> <223> OD111A Light chain <400> 93 Asp Ile Gln Leu Thr Gln Ser Pro Ala Ser Leu Ser Ala Ser Val Gly   1 5 10 15 Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Glu Asn Ile Tyr Ser Tyr              20 25 30 Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro Gln Leu Leu Val          35 40 45 Tyr Asn Ala Lys Thr Leu Ala Glu Gly Val Pro Ser Arg Phe Ser Gly      50 55 60 Ser Gly Ser Gly Thr Gln Phe Ser Leu Lys Ile Asn Ser Leu Gln Pro  65 70 75 80 Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His His Tyr Gly Thr Pro Leu                  85 90 95 Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg Ala Asp Ala Ala             100 105 110 Pro Thr Val Ser         115 <210> 94 <211> 126 <212> PRT <213> Artificial Sequence <220> <223> OD111A Heavy chain <400> 94 Leu Pro Glu Phe Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met   1 5 10 15 Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr              20 25 30 Phe Ser Ser Tyr Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly          35 40 45 Leu Glu Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr      50 55 60 Asn Glu Lys Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser  65 70 75 80 Asn Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala                  85 90 95 Val Tyr Tyr Cys Ala Arg Arg Lys Trp Gly Asn Tyr Val Asn Tyr Tyr             100 105 110 Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Leu         115 120 125 <210> 95 <211> 102 <212> PRT <213> Artificial Sequence <220> <223> OD169B Light chain <400> 95 Met Gln Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly Glu   1 5 10 15 Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met His              20 25 30 Trp Tyr Gln Gln Lys Ser Gly Thr Ser Pro Lys Arg Trp Ile Tyr Asp          35 40 45 Thr Ser Lys Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser Gly      50 55 60 Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Met Glu Ala Glu Asp  65 70 75 80 Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Pro Thr Phe                  85 90 95 Gly Ser Gly Gln Ser Glu             100 <210> 96 <211> 115 <212> PRT <213> Artificial Sequence <220> <223> OD169B Heavy chain <400> 96 Leu Pro Glu Phe Glu Val Gln Leu Glu Glu Ser Gly Pro Gly Leu Val   1 5 10 15 Ala Pro Ser Gln Ser Leu Ser Ile Thr Cys Thr Val Ser Gly Phe Ser              20 25 30 Leu Thr Ser Tyr Gly Val Ser Trp Val Arg Gln Pro Pro Gly Lys Gly          35 40 45 Leu Glu Trp Leu Gly Val Ile Trp Gly Asp Gly Ser Thr Asn Tyr His      50 55 60 Ser Ala Leu Ile Ser Arg Leu Ser Ile Ser Lys Asp Asn Ser Lys Ser  65 70 75 80 Gln Val Phe Leu Lys Leu Asn Ser Leu Gln Thr Asp Asp Thr Ala Thr                  85 90 95 Tyr Tyr Cys Ala Gly Tyr Arg Gly Tyr Trp Gly Gln Gly Thr Leu Val             100 105 110 Thr Thr Pro         115 <210> 97 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> OD184 Light chain <400> 97 Asp Ile Gln Leu Thr Gln Ser Pro Phe Ser Asn Pro Val Thr Leu Gly   1 5 10 15 Thr Ser Ala Ser Ile Ser Cys Arg Ser Ser Lys Ser Leu Leu His Ser              20 25 30 Asn Gly Ile Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser          35 40 45 Pro Gln Leu Leu Ile Tyr Gln Met Ser Asn Leu Ala Ser Gly Val Pro      50 55 60 Asp Arg Phe Ser Ser Ser Gly Ser Gly Thr Asp Phe Thr Leu Arg Ile  65 70 75 80 Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Gln Asn                  85 90 95 Leu Glu Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys             100 105 110 Arg Ala Asp Ala Ala Pro Thr Val Ser         115 120 <210> 98 <211> 125 <212> PRT <213> Artificial Sequence <220> <223> OD184 Heavy chain <400> 98 Leu Pro Glu Phe Gln Val Gln Leu Gln Gln Ser Gly Ser Glu Leu Arg   1 5 10 15 Ser Pro Gly Ser Ser Val Lys Leu Ser Cys Lys Asp Phe Asp Ser Glu              20 25 30 Val Phe Pro Ile Ala Tyr Met Ser Trp Val Arg Gln Lys Pro Gly His          35 40 45 Gly Phe Glu Trp Ile Gly Asp Ile Leu Pro Ser Ile Gly Arg Thr Ile      50 55 60 Tyr Gly Glu Lys Phe Glu Asp Lys Ala Thr Leu Asp Ala Asp Thr Val  65 70 75 80 Ser Asn Thr Ala Tyr Leu Glu Leu Asn Ser Leu Thr Ser Glu Asp Ser                  85 90 95 Ala Ile Tyr Tyr Cys Ala Arg Glu Gly Ser Ser Gly Tyr Gly Ala Trp             100 105 110 Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Leu Cys         115 120 125 <210> 99 <211> 112 <212> PRT <213> Artificial Sequence <220> <223> OD185 Light chain <400> 99 Arg Lys Leu Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Val   1 5 10 15 Ser Ala Gly Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu              20 25 30 Leu Asn Ser Gly Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys          35 40 45 Pro Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu      50 55 60 Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe  65 70 75 80 Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr                  85 90 95 Cys Gln Asn Asp His Ser Tyr Pro Tyr Thr Phe Gly Gly Gly Pro Ser             100 105 110 <210> 100 <211> 125 <212> PRT <213> Artificial Sequence <220> <223> OD185 Heavy chain <400> 100 Leu Pro Glu Phe Gln Val Gln Leu Glu Gln Ser Gly Pro Gly Ile Leu   1 5 10 15 Gln Pro Ser Gln Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser              20 25 30 Leu Ser Thr Ser Gly Met Gly Val Gly Trp Ile Arg Gln Pro Ser Gly          35 40 45 Lys Gly Leu Glu Trp Leu Ala His Ile Trp Trp Asp Asp Asp Lys Arg      50 55 60 Tyr Asn Pro Ala Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser  65 70 75 80 Ser Asn Gln Val Phe Leu Lys Ile Ala Ser Val Asp Thr Ala Asp Thr                  85 90 95 Ala Thr Tyr Tyr Cys Ala Arg Ile Glu Asp Ser Leu Leu Pro Leu Gly             100 105 110 Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Thr Leu         115 120 125 <210> 101 <211> 107 <212> PRT <213> Artificial Sequence <220> <223> OD196 Light chain <400> 101 Cys Arg Lys Leu Asp Ile Gln Leu Thr Gln Ser Pro Lys Phe Met Ser   1 5 10 15 Thr Ser Val Gly Asp Arg Val Ser Val Thr Cys Lys Ala Ser Gln Asn              20 25 30 Val Gly Thr Asn Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro          35 40 45 Lys Ala Leu Ile Tyr Ser Ala Ser Tyr Arg Tyr Ser Gly Val Pro Asp      50 55 60 Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser  65 70 75 80 Asn Val Gln Ser Glu Asp Leu Ala Glu Tyr Phe Cys Gln Gln Tyr Asn                  85 90 95 Ser Tyr Pro Tyr Thr Phe Gly Gly Gly Pro Ser             100 105 <210> 102 <211> 118 <212> PRT <213> Artificial Sequence <220> <223> OD196 Heavy chain <400> 102 Leu Pro Glu Phe Glu Val Gln Leu Gln Glu Ser Gly Pro Glu Leu Val   1 5 10 15 Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Thr Ser Gly Tyr Thr              20 25 30 Phe Thr Glu Tyr Thr Met His Trp Val Lys Gln Ser His Gly Lys Ser          35 40 45 Leu Glu Trp Ile Gly Gly Ile Asn Pro Asn Asn Gly Gly Thr Ser Tyr      50 55 60 Asn Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser  65 70 75 80 Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala                  85 90 95 Val Tyr Tyr Cys Ala Thr Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly             100 105 110 Thr Ser Val Thr Phe Ser         115 <210> 103 <211> 114 <212> PRT <213> Artificial Sequence <220> <223> OD210A Light chain <400> 103 Lys Leu Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser   1 5 10 15 Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser Val Asp              20 25 30 Asn Tyr Gly Ile Ser Phe Met Asn Trp Phe Gln Gln Lys Pro Gly Gln          35 40 45 Pro Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Gln Ser Gly Val      50 55 60 Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ser Leu Asn  65 70 75 80 Ile His Pro Met Glu Glu Asp Asp Thr Ala Met Tyr Phe Cys Gln Gln                  85 90 95 Ser Lys Glu Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Asn Gln             100 105 110 Ser gly         <210> 104 <211> 124 <212> PRT <213> Artificial Sequence <220> <223> OD210A Heavy chain <400> 104 Phe Arg Lys Phe Gln Val Gln Leu Gln Gln Ser Gly Gly Gly Leu Val   1 5 10 15 Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Asp              20 25 30 Phe Ser Arg Tyr Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly          35 40 45 Leu Glu Trp Ile Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr      50 55 60 Thr Pro Ser Leu Lys Asp Lys Phe Ile Ile Ser Arg Asp Asn Ala Lys  65 70 75 80 Asn Thr Leu Tyr Leu Gln Met Ser Lys Val Arg Ser Glu Asp Thr Ala                  85 90 95 Leu Tyr Tyr Cys Ala Arg Arg Gly Ile Tyr Tyr Gly Asn Tyr Cys Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Pro Cys         115 120 <210> 105 <211> 112 <212> PRT <213> Artificial Sequence <220> <223> OD225 Light chain <400> 105 Lys Leu Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Val Ser   1 5 10 15 Ala Gly Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Leu Leu              20 25 30 Asn Ser Gly Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro          35 40 45 Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Thr Arg Glu Ser      50 55 60 Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr  65 70 75 80 Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys                  85 90 95 Gln Asn Asp His Ser Tyr Pro Phe Thr Phe Gly Ser Gly Gln Ser Glu             100 105 110 <210> 106 <211> 121 <212> PRT <213> Artificial Sequence <220> <223> OD225 Heavy chain <400> 106 Leu Pro Glu Phe Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val   1 5 10 15 Lys Pro Gly Thr Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr              20 25 30 Phe Thr Ser Tyr Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly          35 40 45 Leu Glu Trp Ile Gly Asp Ile Tyr Pro Gly Ser Asp Ser Thr Asn Tyr      50 55 60 Asn Glu Lys Phe Lys Ser Lys Ala Thr Leu Thr Val Asp Thr Ser Ser  65 70 75 80 Ser Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala                  85 90 95 Val Tyr Tyr Cys Ala Arg Cys Asp Phe Tyr Trp Tyr Phe Asp Val Trp             100 105 110 Gly Ala Gly Pro Arg Ser Pro Ser Leu         115 120 <210> 107 <211> 108 <212> PRT <213> Artificial Sequence <220> <223> OD234 Light chain <400> 107 Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala Val Ser Leu Gly   1 5 10 15 Gln Arg Ala Thr Ile Ser Tyr Arg Ala Ser Lys Ser Val Ser Thr Ser              20 25 30 Gly Tyr Ser Tyr Met His Trp Asn Gln Gln Lys Pro Gly Gln Pro Pro          35 40 45 Arg Leu Leu Ile Tyr Leu Val Ser Asn Leu Glu Ser Gly Val Pro Ala      50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Asn Ile His  65 70 75 80 Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys Gln His Ile Arg                  85 90 95 Glu Leu Thr Arg Ser Glu Gly Gly Pro Ser Trp Lys             100 105 <210> 108 <211> 127 <212> PRT <213> Artificial Sequence <220> <223> OD234 Heavy chain <400> 108 Leu Ser Glu Phe Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val   1 5 10 15 Lys Pro Gly Ala Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser              20 25 30 Phe Thr Gly Tyr Thr Met Asn Trp Val Ser His Gly Lys Asn Leu Glu          35 40 45 Trp Ile Gly Leu Ile Asn Pro Tyr Asn Gly Gly Thr Ser Tyr Asn Gln      50 55 60 Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr  65 70 75 80 Ala Tyr Met Glu Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr                  85 90 95 Tyr Cys Ala Arg Val Arg Ala Tyr Tyr Gly Asn Tyr Glu Leu Phe Tyr             100 105 110 Trp Tyr Phe Asp Val Trp Gly Ala Gly Pro Arg Ser Pro Ser Pro         115 120 125 <210> 109 <211> 116 <212> PRT <213> Artificial Sequence <220> <223> OD241 Light chain <400> 109 Asp Ile Gln Leu Thr Gln Ser Pro Ala Ser Leu Ser Val Ala Thr Gly   1 5 10 15 Glu Lys Val Thr Ile Arg Cys Ile Thr Ser Thr Asp Ile Asp Asp Asp              20 25 30 Met Asn Trp Tyr Gln Gln Lys Pro Gly Glu Pro Pro Lys Leu Leu Ile          35 40 45 Ser Glu Gly Asn Thr Leu Arg Pro Gly Val Pro Ser Arg Phe Ser Ser      50 55 60 Ser Gly Tyr Gly Thr Asp Phe Val Phe Thr Ile Glu Asn Thr Leu Ser  65 70 75 80 Glu Asp Val Ala Asp Tyr Tyr Cys Leu Gln Ser Asp Asn Met Pro Phe                  85 90 95 Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Arg Arg Ala Asp Ala Ala             100 105 110 Pro Thr Val Ser         115 <210> 110 <211> 124 <212> PRT <213> Artificial Sequence <220> <223> OD241 Heavy chain <400> 110 Phe Arg Lys Phe Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Ile Leu   1 5 10 15 Gln Pro Ser Gln Thr Leu Ser Leu Thr Cys Ser Phe Ser Gly Phe Ser              20 25 30 Leu Ser Thr Ser Gly Met Ser Val Gly Trp Ile Arg Gln Pro Ser Gly          35 40 45 Lys Gly Leu Glu Trp Leu Ala His Ile Trp Trp Asn Asp Asp Lys Tyr      50 55 60 Tyr Asn Pro Ala Leu Lys Ser Arg Leu Thr Ile Ser Lys Asp Thr Ser  65 70 75 80 Asn Asn Gln Val Phe Leu Lys Ile Ala Ser Val Val Thr Ala Asp Thr                  85 90 95 Ala Thr Tyr Tyr Cys Ala Arg Ile Ala Arg Glu Val Arg Arg Tyr Phe             100 105 110 Asp Val Trp Gly Ala Gly Pro Arg Ser Pro Ser Leu         115 120 <210> 111 <211> 107 <212> PRT <213> Artificial Sequence <220> <223> OD244 Light chain <400> 111 Tyr Arg Lys Leu Asp Ile Gln Leu Thr Gln Ser Pro Ala Ile Met Ser   1 5 10 15 Ala Ser Pro Gly Glu Lys Val Thr Ile Ser Cys Ser Ala Ser Ser Ser              20 25 30 Val Ser Tyr Met Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys          35 40 45 Pro Trp Ile Tyr Arg Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg      50 55 60 Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser  65 70 75 80 Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Tyr His Ser                  85 90 95 Tyr Pro Met Tyr Thr Phe Gly Gly Gly Pro Ser             100 105 <210> 112 <211> 122 <212> PRT <213> Artificial Sequence <220> <223> OD244 Heavy chain <400> 112 Leu Pro Glu Ile Glu Val Gln Leu Gln Gln Ser Gly Thr Val Leu Ala   1 5 10 15 Arg Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr              20 25 30 Phe Thr Ser Tyr Trp Met His Trp Val Lys Gln Arg Pro Gly Gln Gly          35 40 45 Leu Glu Trp Ile Gly Ala Ile Tyr Pro Gly Asn Ser Asp Thr Ser Tyr      50 55 60 Asn Gln Lys Phe Lys Gly Lys Ala Lys Leu Thr Ala Val Thr Ser Thr  65 70 75 80 Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Asn Glu Asp Ser Ala                  85 90 95 Val Tyr Tyr Cys Thr Arg Ser Gly Pro Pro Tyr Trp Tyr Phe Asp Val             100 105 110 Trp Gly Ala Gly Pro Arg Ser Pro Pro Tyr         115 120 <210> 113 <211> 111 <212> PRT <213> Artificial Sequence <220> <223> OD270 Light chain <400> 113 Ser Arg Lys Leu Cys Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser   1 5 10 15 Ala Ser Leu Gly Gly Lys Val Thr Ile Thr Cys Lys Ala Ser Gln Asp              20 25 30 Ile Asn Lys Tyr Ile Ala Trp Tyr Gln His Lys Pro Gly Lys Gly Pro          35 40 45 Arg Leu Leu Ile His Tyr Thr Ser Thr Leu Gln Pro Gly Ile Pro Ser      50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Arg Asp Tyr Ser Phe Ser Ile Ser  65 70 75 80 Asn Leu Glu Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Leu Gln Tyr Asp                  85 90 95 Asn Leu Trp Thr Phe Gly Gly Gly Thr Lys Leu Asn Gln Ala Gly             100 105 110 <210> 114 <211> 118 <212> PRT <213> Artificial Sequence <220> <223> OD270 Heavy chain <400> 114 Phe Arg Lys Phe Glu Val Gln Leu Gln Glu Ser Gly Ala Glu Leu Val   1 5 10 15 Arg Pro Gly Ala Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Ser              20 25 30 Phe Thr Ser Tyr Trp Met Asn Trp Val Lys Gln Arg Pro Gly Gln Gly          35 40 45 Leu Glu Trp Ile Gly Met Ile His Pro Ser Asp Ser Glu Thr Arg Leu      50 55 60 Asn Gln Lys Phe Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser  65 70 75 80 Ser Thr Ala Tyr Met Gln Leu Ser Ser Pro Thr Ser Glu Asp Ser Ala                  85 90 95 Val Tyr Tyr Cys Val Asp Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly             100 105 110 Thr Ser Val Thr Val Pro         115 <210> 115 <211> 114 <212> PRT <213> Artificial Sequence <220> <223> OD296 Light chain <400> 115 Arg Lys Leu Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ala Val   1 5 10 15 Thr Ala Gly Glu Lys Val Thr Met Arg Cys Lys Ser Ser Gln Ser Leu              20 25 30 Leu Trp Ser Val Asn Gln Asn Asn Tyr Leu Ser Trp Tyr Gln Gln Lys          35 40 45 Gln Gly Gln Pro Pro Lys Leu Leu Ile Tyr Gly Ala Ser Ile Arg Glu      50 55 60 Ser Trp Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe  65 70 75 80 Thr Leu Thr Ile Ser Asn Val His Ala Glu Asp Leu Ala Val Tyr Tyr                  85 90 95 Cys Gln His Asn His Gly Ser Phe Leu Pro Leu Thr Phe Gly Ala Gly             100 105 110 Pro Ser         <210> 116 <211> 125 <212> PRT <213> Artificial Sequence <220> <223> OD296 Heavy chain <400> 116 Phe Arg Lys Phe Glu Val Gln Leu Gln Glu Ser Gly Pro Glu Leu Val   1 5 10 15 Lys Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr              20 25 30 Phe Thr Ser Tyr Val Met His Trp Val Lys Gln Lys Pro Gly Gln Gly          35 40 45 Leu Glu Trp Ile Gly Tyr Ile Asn Pro Tyr Asn Asp Gly Thr Lys Tyr      50 55 60 Asn Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser  65 70 75 80 Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala                  85 90 95 Val Tyr Tyr Cys Ala Arg Arg Glu Lys Tyr Gly Asn Tyr Val Gly Ala             100 105 110 Met Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Leu         115 120 125 <210> 117 <211> 107 <212> PRT <213> Artificial Sequence <220> <223> OD298 Light chain <400> 117 Tyr Arg Lys Leu Asp Ile Gln Leu Thr Gln Ser Pro Ala Ile Leu Ser   1 5 10 15 Val Ser Pro Gly Glu Arg Val Ser Phe Ser Cys Arg Ala Ser Gln Ser              20 25 30 Ile Gly Thr Ser Ile His Trp Tyr Gln Gln Arg Thr Asn Gly Ser Pro          35 40 45 Arg Leu Leu Ile Lys Tyr Ala Ser Glu Ser Ile Ser Gly Ile Pro Ser      50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Ser Ile Asn  65 70 75 80 Ser Val Glu Ser Glu Asp Ile Ala Asp Tyr Tyr Cys Gln Gln Ser Asn                  85 90 95 Ser Trp Pro Tyr Thr Phe Gly Gly Gly Pro Ser             100 105 <210> 118 <211> 122 <212> PRT <213> Artificial Sequence <220> <223> OD298 Heavy chain <400> 118 Phe Arg Glu Ile Gln Val Gln Leu Gln Glu Ser Gly Pro Glu Leu Val   1 5 10 15 Arg Pro Gly Val Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr              20 25 30 Phe Thr Asp Tyr Ala Met His Trp Val Lys Gln Ser His Ala Lys Ser          35 40 45 Leu Glu Trp Ile Gly Val Ile Ser Thr Tyr Ser Gly Asn Thr Asn Tyr      50 55 60 Asn Gln Lys Phe Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser  65 70 75 80 Ser Thr Ala Tyr Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala                  85 90 95 Ile Tyr Tyr Cys Ala Arg Glu Ala Ser Gly Leu Cys Pro Phe Asp Tyr             100 105 110 Trp Gly Gln Gly Thr Thr Leu Thr Val Pro         115 120 <210> 119 <211> 107 <212> PRT <213> Artificial Sequence <220> <223> OD340 Light chain <400> 119 Arg Ser Glu Ala Cys Ile Gln Leu Thr Gln Ser Pro Ala Ser Leu Tyr   1 5 10 15 Ala Ser Val Gly Glu Thr Val Thr Ile Thr Cys Arg Ala Ser Gly Asn              20 25 30 Ile His Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Gln Gly Lys Ser Pro          35 40 45 Gln Leu Leu Val Tyr Asn Ala Lys Thr Leu Ala Asp Gly Val Pro Ser      50 55 60 Arg Phe Ser Gly Ser Gly Ser Gly Thr Gln Tyr Ser Leu Lys Ile Asn  65 70 75 80 Ser Leu Gln Pro Glu Asp Phe Gly Ser Tyr Tyr Cys Gln His Phe Trp                  85 90 95 Ser Thr Pro Leu Thr Phe Gly Ala Gly Pro Ser             100 105 <210> 120 <211> 123 <212> PRT <213> Artificial Sequence <220> <223> OD340 Heavy chain <400> 120 Leu Pro Glu Ile Glu Val Gln Leu Gln Glu Ser Gly Pro Glu Leu Val   1 5 10 15 Lys Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr              20 25 30 Phe Thr Asp Tyr Asn Met His Trp Val Lys Gln Ser His Gly Lys Ser          35 40 45 Leu Glu Trp Ile Gly Tyr Ile Tyr Pro Tyr Asn Gly Gly Thr Gly Tyr      50 55 60 Asn Gln Lys Phe Lys Ser Lys Ala Thr Leu Thr Val Asp Asn Ser Ser  65 70 75 80 Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp Ser Ala                  85 90 95 Val Tyr Tyr Cys Ala Arg Ala Asp Gly Asn His Pro Tyr Tyr Phe Asp             100 105 110 Tyr Trp Gly Gln Gly Thr Thr Leu Thr Val Leu         115 120 <210> 121 <211> 335 <212> DNA <213> Artificial Sequence <220> <223> OD7 Light chain <400> 121 tttcggaagc ttgacattca gctgacccag tctccagcca ccctgtctgt gactccagga 60 gatagcgtca gtctttcctg cagggccagc caaagtatta gcaacaacct acactggtat 120 caacaaaaat cacatgagtc tccaaggctt ctcatcaagt atgcttccca gtccatctct 180 gggatcccct ccaggttcag tggcagtgga tcagggacag atttcactct cagtatcaac 240 agtgtggaga ctgaagattt tggaatgtat ttctgtcaac agagtaacag ctggccgctc 300 acgttcggtg ctggaccaag ctgagcmaaa cggtt 335 <210> 122 <211> 379 <212> DNA <213> Artificial Sequence <220> <223> OD7 Heavy chain <400> 122 tcttccggaa atttgaggtt cagctgcagc agtctggggc tgagctggtg aggcctggag 60 cttcagtgaa gctgtcctgc aaggcttctg gctactcctt caccagctac tggatgaact 120 gggtgaagca gaggcctgga caaggccttg agtggattgg catgattcat ccttccgata 180 gtgaaactag gttaaatcag aagttcaagg acaaggccac attgactgta gacaaatcct 240 ccagcacagc ctacatgcaa ctcagcagcc cgacatctga ggactctgcg gtctattact 300 gtgcaagacc ggtagtagct acagggaggt actattctat ggactactgg ggtcaaggaa 360 cctcagtcac cgtcccccc 379 <210> 123 <211> 348 <212> DNA <213> Artificial Sequence <220> <223> OD111A Light chain <400> 123 gacattcagc tgacccagtc tccagcctcc ctatctgcat ctgtgggaga aactgtcacc 60 atcacatgtc gagcaagtga gaatatttac agttatttag catggtatca gcagaaacag 120 ggaaaatctc ctcagctcct ggtctataat gcaaaaacct tagcagaagg tgtgccatca 180 aggttcagtg gcagtggatc aggcacacag ttttctctga agatcaacag cctgcagcct 240 gaagattttg ggagttatta ctgtcaacat cattatggta ctccgctcac gttcggtgct 300 gggaccaagc tggagctgaa acgggctgat gctgcaccaa ctgtatcc 348 <210> 124 <211> 381 <212> DNA <213> Artificial Sequence <220> <223> OD111A Heavy chain <400> 124 tcttccggaa ttccaggttc agctgcagca gtctggagct gagctgatga agcctggggc 60 ctcagtgaag atatcctgca aggctactgg ctacacattc agtagctact ggatagagtg 120 ggtaaagcag aggcctggac atggccttga gtggattgga gagattttac ctggaagtgg 180 tagtactaac tacaatgaga agttcaaggg caaggccaca ttcactgcag atacatcctc 240 caacacagcc tacatgcaac tcagcagcct gacatctgag gactctgccg tctattactg 300 tgcaagaagg aaatggggta actacgttaa ttactatgct atggactact ggggtcaagg 360 aacctcagtc accgttctcc c 381 <210> 125 <211> 330 <212> DNA <213> Artificial Sequence <220> <223> OD169B Light chain <400> 125 tctcggaagc ttgaattcag ctgacccagt ctccagcaat catgtctgca tctccagggg 60 agaaggtcac catgacctgc agtgccagct caagtgtaag ttacatgcac tggtaccagc 120 agaagtcagg cacctccccc aaaagatgga tttatgacac atccaaactg gcttctggag 180 tccctgctcg cttcagtggc agtgggtctg ggacctctta ctctctcaca atcagcagca 240 tggaggctga agatgctgcc acttattact gccagcagtg gagtagtaac ccacccacgt 300 tcggctcggg acaaagtgaa taagccggtt 330 <210> 126 <211> 348 <212> DNA <213> Artificial Sequence <220> <223> OD169B Heavy chain <400> 126 tcttccggaa ttcgaggttc agctggagga gtctggacct ggcctggtgg cgccctcaca 60 gagcctgtcc atcacatgca ctgtctcagg gttctcatta accagctatg gtgtaagctg 120 ggttcgccag cctccaggaa agggtctgga gtggctggga gtaatatggg gtgacgggag 180 cacaaattat cattcagctc tcatatccag actgagcatc agcaaggata actccaagag 240 ccaagttttc ttaaaactga acagtctgca aactgatgac acagccacgt actactgtgc 300 cggttaccgc ggttactggg gccaagggac tctggtcacg actccgac 348 <210> 127 <211> 363 <212> DNA <213> Artificial Sequence <220> <223> OD184 Light chain <400> 127 gacattcagc tgacccagtc tccattctcc aatccagtca ctcttggaac atcagcttcc 60 atctcctgca ggtctagtaa gagtctccta catagtaatg gcatcactta tttgtattgg 120 tatctgcaga agccaggcca gtctcctcag ctcctgattt atcagatgtc caaccttgcc 180 tcaggagtcc cagacaggtt cagtagcagt gggtcaggaa ctgatttcac actgagaatc 240 agcagagtgg aggctgagga tgtgggtgtt tattactgtg ctcaaaatct agaacttcct 300 ccgacgttcg gtggaggcac caagctggaa atcaaacggg ctgatgctgc accaactgta 360 tcc 363 <210> 128 <211> 377 <212> DNA <213> Artificial Sequence <220> <223> OD184 Heavy chain <400> 128 tcttccggaa ttccaggttc agctgcagca gtctggttct gaactgagga gtcctgggtc 60 ttcagtaaag ctttcatgca aggattttga ttcagaagtc ttccctattg cttatatgag 120 ttgggttagg cagaagcctg ggcatggatt tgaatggatt ggagacatac tcccaagtat 180 tggtagaaca atctatggag agaagtttga ggacaaagcc acactggatg cagacacagt 240 gtccaacaca gcctacttgg agctcaacag tctgacatct gaggactctg ctatctacta 300 ctgtgcaagg gagggcagct cgggctacgg ggcctggttt gcttactggg gccaagggac 360 tctggtcact ctctgcc 377 <210> 129 <211> 351 <212> DNA <213> Artificial Sequence <220> <223> OD185 Light chain <400> 129 tcggaagctt gacattcagc tgacccagtc tccatcctcc ctgagtgtgt cagcaggaga 60 gaaggtcact atgagctgca agtccagtca gagtctgtta aacagtggaa atcaaaagaa 120 ctacttggcc tggtaccagc agaaaccagg gcagcctcct aaactgttga tctacggggc 180 atccactagg gaatctgggg tccctgatcg cttcacaggc agtggatctg gaaccgattt 240 cactcttacc atcagcagtg tgcaggctga agacctggca gtttattact gtcagaatga 300 tcatagttat ccgtacacgt tyggaggggg accaagctga aataataggt t 351 <210> 130 <211> 351 <212> DNA <213> Artificial Sequence <220> <223> OD185 Heavy chain <400> 130 tcggaagctt gacattcagc tgacccagtc tccatcctcc ctgagtgtgt cagcaggaga 60 gaaggtcact atgagctgca agtccagtca gagtctgtta aacagtggaa atcaaaagaa 120 ctacttggcc tggtaccagc agaaaccagg gcagcctcct aaactgttga tctacggggc 180 atccactagg gaatctgggg tccctgatcg cttcacaggc agtggatctg gaaccgattt 240 cactcttacc atcagcagtg tgcaggctga agacctggca gtttattact gtcagaatga 300 tcatagttat ccgtacacgt tyggaggggg accaagctga aataataggt t 351 <210> 131 <211> 335 <212> DNA <213> Artificial Sequence <220> <223> OD196 Light chain <400> 131 tgtcggaagc ttgacattca gctgacccag tctccaaaat tcatgtccac atcagtagga 60 gacagggtca gcgtcacctg caaggccagt cagaatgtgg gtactaatgt agcctggtat 120 caacagaaac cagggcaatc tcctaaagca ctgatttact cggcatccta ccggtacagt 180 ggagtccctg atcgcttcac aggcagtgga tctgggacag atttcactct caccatcagc 240 aatgtgcagt ctgaagactt ggcagagtat ttctgtcagc aatataacag ctatccgtac 300 acgttcggag ggggaccaag ctgaataaac gggtt 335 <210> 132 <211> 355 <212> DNA <213> Artificial Sequence <220> <223> OD196 Heavy chain <400> 132 tcttccggaa ttcgaggttc agctgcagga gtctggacct gagctggtga agcctggggc 60 ttcagtgaag atatcctgca agacttctgg atacacattc actgaataca ccatgcactg 120 ggtgaagcag agccatggaa agagccttga gtggattgga ggtattaatc ctaacaatgg 180 tggtactagc tacaaccaga agttcaaggg caaggccaca ttgactgtag acaagtcctc 240 cagcacagcc tacatggagc tccgcagcct gacatctgag gattctgcag tctattactg 300 tgcaactggg tatgctatgg actactgggg tcaaggaacc tcagtcacct tctcc 355 <210> 133 <211> 351 <212> DNA <213> Artificial Sequence <220> <223> OD210A Light chain <133> 133 ttttttggaa gcttgacatt gtgctgaccc aatctccagc ttctttggct gtgtctctag 60 ggcagagggc caccatctcc tgcagagcca gcgaaagtgt tgataattat ggcattagtt 120 ttatgaactg gttccaacag aaaccaggac agccacccaa actcctcatc tatgctgcat 180 ccaaccaagg atccggggtc cctgccaggt ttagtggcag tgggtctggg acagacttca 240 gcctcaacat ccatcctatg gaggaggatg atactgcaat gtatttctgt cagcaaagta 300 aggaggttcc tcggacgttc ggtggaggca ccaagctgaa tcaaagcggt t 351 <210> 134 <211> 375 <212> DNA <213> Artificial Sequence <220> <223> OD210A Heavy chain <400> 134 tcttccggaa attccaggtt cagctgcagc agtctggagg tggcctggtg cagcctggag 60 gatccctgaa actctcctgt gcagcctcag gattcgattt tagtagatac tggatgagtt 120 gggtccggca ggctccaggg aaagggctag aatggattgg agaaattaat ccagatagca 180 gtacgataaa ctatacgcca tctctaaagg ataaattcat catctccaga gacaacgcca 240 aaaatacgct gtacctgcaa atgagcaaag tgagatctga ggacacagcc ctttattact 300 gtgcaagacg gggaatctac tatggtaact actgtgacta ctggggccaa ggcaccactc 360 tcacagttcc ctgcc 375 <210> 135 <211> 349 <212> DNA <213> Artificial Sequence <220> <223> OD225 Light chain <400> 135 ggaagcttga cattcagctg acccagtctc catcctccct gagtgtgtca gcaggagaga 60 aggtcactat gagctgcaag tccagtcaga gtctgttaaa cagtggaaat caaaagaact 120 acttggcctg gtaccagcag aaaccagggc agcctcctaa actgttgatc tacggggcat 180 ccactaggga atctggggtc cctgatcgct tcacaggcag tggatctgga accgatttca 240 ctcttaccat cagcagtgtg caggctgaag acctggcagt ttattactgt cagaatgatc 300 atagttatcc attcacgttc ggctcgggac aaagtgaata aagcgggtt 349 <210> 136 <211> 365 <212> DNA <213> Artificial Sequence <220> <223> OD225 Heavy chain <400> 136 tcttccggaa tttcaggttc agctgcagca gtctggggct gaactggtga agcctgggac 60 ttcagtgaaa atgtcctgca aggcttctgg ctacaccttc accagctact ggatgcactg 120 ggtgaagcag aggccgggac aaggccttga gtggattgga gatatttatc ctggtagtga 180 tagtactaac tacaatgaga agttcaagag caaggccaca ctgactgtag acacatcctc 240 cagcacagcc tacatgcaac tcagcagcct gacatctgag gactctgcgg tctattactg 300 tgcaaggtgc gacttttact ggtacttcga tgtctggggc gcaggaccac ggtcaccgtc 360 cctag 365 <210> 137 <211> 356 <212> DNA <213> Artificial Sequence <220> <223> OD234 Light chain <400> 137 gacattgtgc tgacccaatc tccagcttct ttagctgtat ctctggggca gagggccacc 60 atctcataca gggccagcaa aagtgtcagt acatctggct atagttatat gcactggaac 120 caacagaaac caggacagcc acccagactc ctcatctatc ttgtatccaa cctagaatct 180 ggggtccctg ccaggttcag tggcagtggg tctgggacag acttcaccct caacatccat 240 cctgtggagg aggaggatgc tgcaacctat tactgtcagc acattaggga gcttacacgt 300 tcggaggggg gaccaagctg gaaataaaac gggctgatgc tgcaccaact gtatcc 356 <210> 138 <211> 383 <212> DNA <213> Artificial Sequence <220> <223> OD234 Heavy chain <400> 138 tctttcggaa tttgaggtcc agctgcagca gtcaggacct gagctggtga agcctggagc 60 ttcaatgaag atatcctgca aggcttctgg ttactcattc actggctaca ccatgaactg 120 ggtgagccat ggaaagaacc ttgagtggat tggacttatt aatccttaca atggtggtac 180 tagctacaac cagaagttca agggcaaggc cacattaact gtagacaagt catccagcac 240 agcctacatg gagctcctca gtctgacatc tgaggactct gcagtctatt actgtgcaag 300 agttagggcc tactatggta actacgagct tttttactgg tacttcgatg tctggggcgc 360 aggaccacgg tcaccgtccc ccc 383 <139> <211> 348 <212> DNA <213> Artificial Sequence <220> <223> OD241 Light chain <400> 139 gacattcagc tgacccagtc tccagcatcc ctgtccgtgg ctacaggaga aaaagtcact 60 atcagatgca taaccagcac tgatattgat gatgatatga actggtacca gcagaagcca 120 ggggaacctc ctaagctcct tatttcagaa ggcaatactc ttcgtcctgg agtcccatcc 180 cgattctcca gcagtggcta tggcacagat tttgttttta caattgaaaa cacgctctca 240 gaagatgttg cagattacta ctgtttgcaa agtgataaca tgccattcac gttcggctcg 300 gggacaaagt tggaaataag acgggctgat gctgcaccaa ctgtatcc 348 <210> 140 <211> 376 <212> DNA <213> Artificial Sequence <220> <223> OD241 Heavy chain <400> 140 tcttccggaa attccaggtt cagctgcagg agtctggccc tgggatattg cagccctccc 60 agaccctcag tctgacttgt tctttctctg ggttttcact gagcacttct ggtatgagtg 120 taggctggat tcgtcagcct tcagggaagg gtctggagtg gctggcacac atttggtgga 180 atgatgataa gtactataac ccagccctga aaagccggct cacaatctcc aaggatacct 240 ccaacaacca ggtattcctc aagatcgcca gtgtggtcac tgcagatact gccacatact 300 actgtgctcg aatagctagg gaggtacgac ggtacttcga tgtctggggc gcaggaccac 360 ggtcaccttc cctccc 376 <210> 141 <211> 335 <212> DNA <213> Artificial Sequence <220> <223> OD244 Light chain <400> 141 tatcggaagc ttgacattca gctgacccag tctccagcaa tcatgtctgc atctccaggg 60 gagaaggtca ccatatcctg cagtgccagc tcaagtgtaa gttacatgta ctggtaccag 120 cagaagccag gatcctcccc caaaccctgg atttatcgca catccaacct ggcttctgga 180 gtccctgctc gcttcagtgg cagtgggtct gggacctctt actctctcac aatcagcagc 240 atggaggctg aagatgctgc cacttattac tgccagcagt atcatagtta ccccatgtac 300 acgttcggag ggggaccaag ctgaaataaa cggtt 335 <210> 142 <211> 367 <212> DNA <213> Artificial Sequence <220> <223> OD244 Heavy chain <400> 142 tcttccggaa attgaggttc agctgcagca gtctgggact gtgctggcaa ggcctggggc 60 ttcagtgaag atgtcctgca aggcttctgg ctacaccttt accagctact ggatgcactg 120 ggtaaaacag aggcctggac agggtctgga atggattggc gctatttatc ctggaaatag 180 tgatactagc tacaaccaga agttcaaggg caaggccaaa ctgactgcag tcacatccac 240 cagcactgcc tacatggagc tcagcagcct gacaaatgag gactctgcgg tctattactg 300 tacaagatcc gggcccccat actggtactt cgatgtctgg ggcgcaggac cacggtcacc 360 tccctac 367 <210> 143 <211> 334 <212> DNA <213> Artificial Sequence <220> <223> OD270 Light chain <400> 143 tctcggaagc tttgcattca gctgacccag tctccatcct cactgtctgc atctctggga 60 ggcaaagtca ccatcacttg caaggcaagc caagacatta acaagtatat agcttggtac 120 caacacaagc ctggaaaagg tcctaggctg ctcatacatt acacatctac attacagcca 180 ggcatcccat caaggttcag tggaagtggg tctgggagag attattcctt cagcatcagc 240 aacctggagc ctgaagatat tgcaacttat tattgtctac agtatgataa tctgtggacg 300 ttcggtggag gcaccaagct gaatcaagcg ggtt 334 <210> 144 <211> 360 <212> DNA <213> Artificial Sequence <220> <223> OD270 Heavy chain <400> 144 tctcttccgg aaatttgagg ttcagctgca ggagtctggg gctgagctgg tgaggcctgg 60 agcttcagtg aagctgtcct gcaaggcttc tggctactcc ttcaccagct actggatgaa 120 ctgggtgaag cagaggcctg gacaaggcct tgagtggatt ggcatgattc atccttccga 180 tagtgaaact aggttaaatc agaagttcaa ggacaaggcc acattgactg tagacaaatc 240 ctccagcaca gcctacatgc aactcagcag cccgacatct gaggactctg cggtctatta 300 ctgtgttgat ggctatgcta tggactactg gggtcaagga acctcagtca ccgttcctcc 360                                                                          360 <210> 145 <211> 358 <212> DNA <213> Artificial Sequence <220> <223> OD296 Light chain <400> 145 tcggaagctt gacattcagc tgacccagtc tccatcctcc ctggctgtga cagcaggaga 60 gaaggtcact atgagatgca agtccagtca gagtcttttg tggagtgtaa accaaaataa 120 ctacttatcc tggtaccagc agaaacaagg gcagcctcct aaactgctta tctatggggc 180 atccattaga gaatcttggg tccctgatcg attcacagga agtggatctg ggacagactt 240 cactctcacc attagcaatg tgcatgctga agacctagca gtttattact gtcagcacaa 300 tcatggcagc tttctccccc tcacgttcgg tgctggacca agctgagcma agcgggtt 358 <210> 146 <211> 378 <212> DNA <213> Artificial Sequence <220> <223> OD296 Heavy chain <400> 146 tcttccggaa atttgaggtt cagctgcagg agtctggacc tgagctggta aagcctgggg 60 cttcagtgaa gatgtcctgc aaggcttctg gatacacatt cactagctat gttatgcact 120 gggtgaagca gaagcctggg cagggccttg agtggattgg atatattaat ccttacaatg 180 atggtactaa gtacaatgag aagttcaaag gcaaggccac actgacttca gacaaatcct 240 ccagcacagc ctacatggag ctcagcagcc tgacctctga ggactctgcg gtctattact 300 gtgcaagaag ggaaaagtat ggtaactacg tgggggctat ggactactgg ggtcaaggaa 360 cctcagtcac cgtcctcc 378 <210> 147 <211> 335 <212> DNA <213> Artificial Sequence <220> <223> OD298 Light chain <400> 147 tatcggaagc ttgacattca gctgacccag tctccagcca tcctgtctgt gagtccagga 60 gaaagagtca gtttctcctg cagggccagt cagagcattg gcacaagcat acactggtat 120 cagcaaagaa caaatggttc tccaaggctt ctcataaagt atgcttctga gtctatctct 180 gggatccctt ccaggtttag tggcagtgga tcagggacag attttactct tagcatcaac 240 agtgtggagt ctgaagatat tgcagattat tactgtcaac aaagtaatag ctggccgtac 300 acgttcggag ggggaccaag ctgaataagc gggtt 335 <210> 148 <211> 370 <212> DNA <213> Artificial Sequence <220> <223> OD298 Heavy chain <400> 148 tcttccggga aattcaggtt cagctgcagg agtctgggcc tgagctggtg aggcctgggg 60 tctcagtgaa gatttcctgc aagggttccg gctacacatt cactgattat gctatgcact 120 gggtgaagca gagtcatgca aagagtctag agtggattgg agttattagt acttactctg 180 gtaatacaaa ctacaaccag aagtttaagg gcaaggccac aatgactgta gacaaatcct 240 ccagcacagc ctatatggaa cttgccagat tgacatctga ggattctgcc atctattact 300 gtgcaagaga ggcatccgga ctatgccctt ttgactactg gggccaaggc accactctca 360 cagtccctcc 370 <210> 149 <211> 335 <212> DNA <213> Artificial Sequence <220> <223> OD340 Light chain <400> 149 cggtcggaag cttgcattca gctgacccag tctccagcct ccctatatgc atctgtggga 60 gaaactgtca ccatcacatg tcgagcaagt gggaatattc acaattattt agcatggtat 120 cagcagaaac agggaaaatc tcctcagctc ctggtttata atgcaaaaac cttagcagat 180 ggtgtgccat caaggttcag tggcagtgga tcaggaacac aatattctct caagatcaac 240 agcctgcagc ctgaagattt tgggagttat tactgtcaac atttttggag tactccgctc 300 acgttcggtg ctggaccaag ctgagctaat cggat 335 <210> 150 <211> 372 <212> DNA <213> Artificial Sequence <220> <223> OD340 Heavy chain <400> 150 tcttccggaa attgaggtgc agctgcagga gtcaggacct gagctggtga aacctggggc 60 ctcagtgaag atatcctgca aggcttctgg atacacattc actgactaca acatgcactg 120 ggtgaagcag agccatggaa agagccttga gtggattgga tatatttatc cttacaatgg 180 tggtactggc tacaaccaga agttcaagag caaggccaca ttgactgtag acaattcctc 240 cagcacagcc tacatggagc tccgcagcct gacatctgag gactctgcag tctattactg 300 tgcaagagcg gatggtaacc acccctacta ctttgactac tggggccaag gcaccactct 360 cacagtcctg ac 372

Claims (43)

a) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 1, a light chain CDR2 represented by SEQ ID NO: 2, a light chain CDR3 represented by SEQ ID NO: 3, a heavy chain CDR1 represented by SEQ ID NO: 4, represented by SEQ ID NO: 5 An oblast-specific OD7 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 6;
b) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 7, a light chain CDR2 represented by SEQ ID NO: 8, a light chain CDR3 represented by SEQ ID NO: 9, a heavy chain CDR1 represented by SEQ ID NO: 10, represented by SEQ ID NO: 11 An oblast-specific OD111A IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 12;
c) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 13, a light chain CDR2 represented by SEQ ID NO: 14, a light chain CDR3 represented by SEQ ID NO: 15, a heavy chain CDR1 represented by SEQ ID NO: 16, represented by SEQ ID NO: 17 An oblast-specific OD169B IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 18;
d) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 19, a light chain CDR2 represented by SEQ ID NO: 20, a light chain CDR3 represented by SEQ ID NO: 21, a heavy chain CDR1 represented by SEQ ID NO: 22, represented by SEQ ID NO: 23 An oblast-specific OD184 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 24;
e) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 25, a light chain CDR2 represented by SEQ ID NO: 26, a light chain CDR3 represented by SEQ ID NO: 27, a heavy chain CDR1 represented by SEQ ID NO: 28, represented by SEQ ID NO: 29 An oblast-specific OD185 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 30;
f) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 31, a light chain CDR2 represented by SEQ ID NO: 32, a light chain CDR3 represented by SEQ ID NO: 33, a heavy chain CDR1 represented by SEQ ID NO: 34, represented by SEQ ID NO: 35 An oblast-specific OD196 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 36;
g) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 37, a light chain CDR2 represented by SEQ ID NO: 38, a light chain CDR3 represented by SEQ ID NO: 39, a heavy chain CDR1 represented by SEQ ID NO: 40, represented by SEQ ID NO: 41 An oblast-specific OD210A IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 42;
h) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 43, a light chain CDR2 represented by SEQ ID NO: 44, a light chain CDR3 represented by SEQ ID NO: 45, a heavy chain CDR1 represented by SEQ ID NO 46, represented by SEQ ID NO 47 An oblast-specific OD225 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 48;
i) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 49, a light chain CDR2 represented by SEQ ID NO: 50, a light chain CDR3 represented by SEQ ID NO: 51, a heavy chain CDR1 represented by SEQ ID NO: 52, represented by SEQ ID NO: 53 An oblast-specific OD234 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 54;
j) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 55, a light chain CDR2 represented by SEQ ID NO: 56, a light chain CDR3 represented by SEQ ID NO: 57, a heavy chain CDR1 represented by SEQ ID NO: 58, represented by SEQ ID NO: 59 An oblast-specific OD241 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 60;
k) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 61, a light chain CDR2 represented by SEQ ID NO: 62, a light chain CDR3 represented by SEQ ID NO: 63, a heavy chain CDR1 represented by SEQ ID NO: 64, represented by SEQ ID NO: 65; An oblast-specific OD244 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 66;
l) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 67, a light chain CDR2 represented by SEQ ID NO: 68, a light chain CDR3 represented by SEQ ID NO: 69, a heavy chain CDR1 represented by SEQ ID NO: 70, represented by SEQ ID NO: 71; An oblast-specific OD270 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 72;
m) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 73, a light chain CDR2 represented by SEQ ID NO: 74, a light chain CDR3 represented by SEQ ID NO: 75, a heavy chain CDR1 represented by SEQ ID NO: 76, represented by SEQ ID NO: 77 An oblast-specific OD296 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 78;
n) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 79, a light chain CDR2 represented by SEQ ID NO: 80, a light chain CDR3 represented by SEQ ID NO: 81, a heavy chain CDR1 represented by SEQ ID NO: 82, represented by SEQ ID NO: 83 An oblast-specific OD298 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 84; And
o) a light chain variable region comprising a light chain CDR1 represented by SEQ ID NO: 85, a light chain CDR2 represented by SEQ ID NO: 86, a light chain CDR3 represented by SEQ ID NO: 87, a heavy chain CDR1 represented by SEQ ID NO: 88, represented by SEQ ID NO: 89 An oblast-specific OD340 IgM antibody comprising a heavy chain variable region comprising a heavy chain CDR2 and a heavy chain CDR3 represented by SEQ ID NO: 90; One oocyte-specific IgM monoclonal antibody selected from the group consisting of.
According to claim 1, The a) OD7 IgM antibody is characterized in that it comprises a light chain variable region represented by SEQ ID NO: 91 and a heavy chain variable region represented by SEQ ID NO: 92, the oocyte specific IgM monoclonal antibody.
The light chain variable region of the a) OD7 IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 121, and the heavy chain variable region is encoded by the nucleotide sequence represented by SEQ ID NO: 122. , Oblast-specific IgM monoclonal antibody.
The oocyte-specific IgM monoclonal antibody of claim 1, wherein the b) OD111A IgM antibody comprises a light chain variable region represented by SEQ ID NO: 93 and a heavy chain variable region represented by SEQ ID NO: 94. 7.
The light chain variable region of b) the OD111A IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 123, and the heavy chain variable region is encoded by the nucleotide sequence represented by SEQ ID NO: 124. , Oblast-specific IgM monoclonal antibody.
The oocyte-specific IgM monoclonal antibody of claim 1, wherein the c) OD169B IgM antibody comprises a light chain variable region represented by SEQ ID NO: 95 and a heavy chain variable region represented by SEQ ID NO: 96. 4.
The light chain variable region of c) OD169B IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 125, and the heavy chain variable region is encoded by the nucleotide sequence represented by SEQ ID NO: 126. , Oblast-specific IgM monoclonal antibody.
According to claim 1, The d) OD184 IgM antibody is characterized in that it comprises a light chain variable region represented by SEQ ID NO: 97 and a heavy chain variable region represented by SEQ ID NO: 98, the oocyte specific IgM monoclonal antibody.
The method according to claim 8, wherein d) the light chain variable region of the OD184 IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 127, heavy chain variable region is characterized in that encoded by the nucleotide sequence represented by SEQ ID NO: 128. Oblast-specific IgM monoclonal antibody
According to claim 1, The e) OD185 IgM antibody is characterized in that it comprises a light chain variable region represented by SEQ ID NO: 99 and a heavy chain variable region represented by SEQ ID NO: 100, the oocyte-specific IgM monoclonal antibody.
The method of claim 10, wherein e) the light chain variable region of the OD185 IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 129, the heavy chain variable region is characterized in that encoded by the base sequence represented by SEQ ID NO: 130. Oblast-specific IgM monoclonal antibody
The oocyte-specific IgM monoclonal antibody of claim 1, wherein the fOD OD196 IgM antibody comprises a light chain variable region represented by SEQ ID NO: 101 and a heavy chain variable region represented by SEQ ID NO: 102. 7.
The light chain variable region of f) OD196 IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 131, and the heavy chain variable region is encoded by the nucleotide sequence represented by SEQ ID NO: 132. , Oblast-specific IgM monoclonal antibody.
The oocyte-specific IgM monoclonal antibody according to claim 1, wherein the g) OD210A IgM antibody comprises a light chain variable region represented by SEQ ID NO: 103 and a heavy chain variable region represented by SEQ ID NO: 104.
The light chain variable region of g) OD210A IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 133, and the heavy chain variable region is encoded by the nucleotide sequence represented by SEQ ID NO: 134. , Oblast-specific IgM monoclonal antibody.
The oocyte-specific IgM monoclonal antibody of claim 1, wherein the h) OD225 IgM antibody comprises a light chain variable region represented by SEQ ID NO: 105 and a heavy chain variable region represented by SEQ ID NO: 106.
The method according to claim 16, wherein h) the light chain variable region of the OD225 IgM antibody is encoded by a nucleotide sequence represented by SEQ ID NO: 135, the heavy chain variable region is characterized by a nucleotide sequence represented by SEQ ID NO: 136 , Oblast-specific IgM monoclonal antibody.
According to claim 1, The i) OD234 IgM antibody is characterized in that it comprises a light chain variable region represented by SEQ ID NO: 107 and a heavy chain variable region represented by SEQ ID NO: 108, the odontoblast specific IgM monoclonal antibody.
19. The method of claim 18, wherein i) the light chain variable region of the OD234 IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 137, heavy chain variable region is characterized in that encoded by the base sequence represented by SEQ ID NO: 138. , Oblast-specific IgM monoclonal antibody.
The oocyte-specific IgM monoclonal antibody of claim 1, wherein the j) OD241 IgM antibody comprises a light chain variable region represented by SEQ ID NO: 109 and a heavy chain variable region represented by SEQ ID NO: 110.
The method according to claim 20, wherein j) the light chain variable region of the OD241 IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 139, heavy chain variable region is characterized in that the encoded by the nucleotide sequence represented by SEQ ID NO: 140. , Oblast-specific IgM monoclonal antibody.
The oocyte-specific IgM monoclonal antibody of claim 1, wherein the OD244 IgM antibody comprises a light chain variable region represented by SEQ ID NO: 111 and a heavy chain variable region represented by SEQ ID NO: 112. 7.
The light chain variable region of k) OD244 IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 141, and the heavy chain variable region is encoded by the nucleotide sequence represented by SEQ ID NO: 142. , Oblast-specific IgM monoclonal antibody.
The oocyte-specific IgM monoclonal antibody of claim 1, wherein the l) OD270 IgM antibody comprises a light chain variable region represented by SEQ ID NO: 113 and a heavy chain variable region represented by SEQ ID NO: 114.
The light chain variable region of l) OD270 IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 143, and the heavy chain variable region is encoded by the nucleotide sequence represented by SEQ ID NO: 144. , Oblast-specific IgM monoclonal antibody.
According to claim 1, wherein m) OD296 IgM antibody is characterized in that it comprises a light chain variable region represented by SEQ ID NO: 115 and a heavy chain variable region represented by SEQ ID NO: 116, an oblast-specific IgM monoclonal antibody.
The light chain variable region of m) OD296 IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 145, and the heavy chain variable region is encoded by the nucleotide sequence represented by SEQ ID NO: 146. , Oblast-specific IgM monoclonal antibody.
The oocyte-specific IgM monoclonal antibody of claim 1, wherein the n) OD298 IgM antibody comprises a light chain variable region represented by SEQ ID NO: 117 and a heavy chain variable region represented by SEQ ID NO: 118.
The method according to claim 28, wherein n) the light chain variable region of the OD298 IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 147, heavy chain variable region is characterized in that the encoded by the nucleotide sequence represented by SEQ ID NO: 148. , Oblast-specific IgM monoclonal antibody.
The oocyte-specific IgM monoclonal antibody of claim 1, wherein the o) OD340 IgM antibody comprises a light chain variable region represented by SEQ ID NO: 119 and a heavy chain variable region represented by SEQ ID NO: 120.
The method of claim 30, wherein o) the light chain variable region of the OD340 IgM antibody is encoded by the nucleotide sequence represented by SEQ ID NO: 149, the heavy chain variable region is characterized in that encoded by the nucleotide sequence represented by SEQ ID NO: 150. , Oblast-specific IgM monoclonal antibody.
32. The odontoblast specific IgM monoclonal antibody of any one of claims 1 to 31, characterized in that it specifically binds to the differentiated odontoblast surface.
33. The method according to claim 32, wherein the differentiated oocyte progenitor cells are differentiated from pulp stem cells into odontoblasts by treatment of bone morphogenetic protein 2 (BMP2) and bone morphogenetic protein 4 (BMP4). IgM monoclonal antibody.
32. A hybridoma cell line producing the oblast-specific IgM monoclonal antibody of any one of claims 1-31.
32. A composition for identifying differentiated odontoblasts, comprising the oblast-specific IgM monoclonal antibody of any one of claims 1-31.
32. A kit for identifying differentiated odontoblasts, comprising the oocyte-specific IgM monoclonal antibody of any one of claims 1-31.
32. A method comprising: treating a sample with the oblast-specific IgM monoclonal antibody of any one of claims 1-31; Differentiated odontoblast identification method comprising a.
32. A composition for separating odontoblasts comprising the oocyte specific IgM monoclonal antibody of any one of claims 1 to 31.
32. A kit for the isolation of odontoblasts comprising the oocyte-specific IgM monoclonal antibody of any one of claims 1-31.
a) treating a sample with the oblast-specific IgM monoclonal antibody of any one of claims 1-31; And
b) separating the antibody bound to the odontoblast; Method for separating odontoblasts comprising a.
32. A composition for screening differentiation promoting substances for promoting differentiation of undifferentiated pulp stem cells into odontoblasts, comprising the oocyte-specific IgM monoclonal antibody of any one of claims 1 to 31.
32. A kit for screening differentiation promoting substances for promoting differentiation of undifferentiated pulp stem cells into odontoblasts, comprising the oocyte-specific IgM monoclonal antibody of any one of claims 1 to 31.
a) treating undifferentiated pulp stem cells with the oblast-specific IgM monoclonal antibody of any one of claims 1-31;
b) treating the candidate with undifferentiated pulp stem cells; And
c) treating the sample with the oblast-specific IgM monoclonal antibody of any one of claims 1 to 31 to compare the binding reaction with step a) above; The method of screening a substance for differentiating undifferentiated pulp stem cells into odontoblasts comprising a.

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