RU2819627C1 - ANTI-C10orf54 ANTIBODIES AND APPLICATIONS THEREOF - Google Patents

Abstract

FIELD: biotechnology.

SUBSTANCE: invention relates to an isolated antibody or its antigen-binding fragment, which binds to C10orf54 proteins, a method for production thereof, as well as to a conjugate containing it. Also disclosed is a polynucleotide coding an anti-C10orf54 antibody, as well as a cell and a vector containing same.

EFFECT: invention is effective for detecting C10orf54 protein in a sample in vitro, as well as for detecting or diagnosing in vitro a C10orf54-mediated disease in a subject.

19 cl, 30 dwg, 42 tbl, 9 ex

Description

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to United States Provisional Application No. 62/090880, filed December 11, 2014, the contents of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention generally relates to antibodies to C10orf54, including antibody-drug conjugates containing these antibodies, and methods of using them.

BACKGROUND ART

C10orf54 (a protein encoded by the gene from open reading frame 54 on chromosome 10) is a single-spanning type I transmembrane protein that consists of 311 amino acids and includes a signal sequence and one IgV-like domain in its intracellular region. It is a potential member of the B7 family of proteins and shares approximately 24% sequence identity with B7-H1/PD-L1 (Flajnik et al., Immunogenetic, 64: 571-590 (2012)). The murine orthologue of C10orf54 is known as a suppressor of T cell activation containing immunoglobulin V region (VISTA; also known as PD-L3). VISTA was cloned from a CD4-positive regulatory T cell library (T _reg ) (Wang et al., JEM, 208(3): 577-592 (2011)). VISTA is expressed primarily on hematopoietic cells, and VISTA expression is highly regulated on myeloid antigen presenting cells (APCs) and T cells (Wang et al., supra).

VISTA appears to have functional activities that are not duplicated by other members of the Ig superfamily and may play a role in the development of autoimmunity and immune surveillance in cancer. For example, expression of a VISTA-Ig fusion protein has been shown to inhibit T cell proliferation and cytokine production in vitro, and overexpression of VISTA on MCA105 tumor cells has been shown to interfere with host protective antitumor immunity (Wang et al., supra). In addition, administration of a VISTA-specific monoclonal antibody (mAb) enhanced the CD4-positive T cell response in vivo and the development of an autoimmune reaction (Wang et al., supra). Monoconeal antibodies to C10orf54 have also been shown to prevent the development of acute graft-versus-host disease in mice (Flies et al., J. Immunology, 187(4): 1537-1541 (2011)).

The citation or discussion of a reference in this specification should not be construed as an admission that it is prior art to the present invention.

BRIEF DESCRIPTION OF THE INVENTION

The present invention provides antibodies that bind to C10orf54, including humanized antibodies and antibody-drug conjugates containing these humanized antibodies, and methods of using antibodies and antibody-drug conjugates, including for the diagnosis and treatment of malignancies. The present invention further provides proteins that bind to C10orf54, including binding proteins, such as antibodies, that bind to one or more C10orf54 proteins or chimeric proteins. Such binding proteins, including antibodies, may be antagonists (eg, those that inhibit one or more biological activities of C10orf54).

In a first aspect, this application provides antibodies that bind to C10orf54, including a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope, collectively referred to herein as anti-C10orf54 antibodies. In addition, this application provides antibodies to C10orf54 that are conjugated to drugs in the form of antibody-drug conjugates (ADCs), including ADCs of the formula A-L-CTX, where A is an antibody, L is a linker, and CTX is a cytotoxin . In some embodiments, anti-C10orf54 antibodies are humanized antibodies that bind to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope. In certain embodiments, the anti-C10orf54 antibody comprises a VH domain (variable heavy chain domain), VL domain (variable light chain domain), VH CDR1 (complementarity determining region 1), VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3 monoclonal antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 3 53A or 305A, described in this application (for example, in Tables 12-33), or a humanized version thereof. In certain embodiments, the anti-C10orf54 antibody may further comprise VH FR1 (framework region 1), VH FR2, VH FR3, VH FR4, VL FR1, VL FR2, VL FR3 and/or VL FR4 from a human germline immunoglobulin amino acid sequence or variant thereof.

In certain embodiments, the antibody contains less than six CDRs. In some embodiments, the antibody contains one, two, three, four, or five, or consists of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and /or VL CDR3. In specific embodiments, the antibody contains one, two, three, four, or five, or consists of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and /or VL CDR3 monoclonal antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 353A or 305A, described in this application (for example, in Tables 12-33), or a humanized version thereof. In specific embodiments, the antibody further comprises VH FR1, VH FR2, VH FR3, VH FR4, VL FR1, VL FR2, VL FR3 and/or VL FR4 from a human germline immunoglobulin amino acid sequence or variant thereof.

In specific embodiments, the antibody is a humanized antibody, a monopoly antibody, a recombinant antibody, an antigen binding fragment, or any combination thereof. In specific embodiments, the antibody is a humanized monopoly antibody as described herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A described in this application (for example, in Tables 12-33), containing a VH domain, a VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and /or VL CDR3), or an antigen binding fragment thereof, that binds to a C10orf54 polypeptide (eg, cell surface expressed or soluble C10orf54), a fragment of C10orf54, or a C10orf54 epitope.

In a second aspect, this application provides antibodies, including humanized antibodies, (1) that competitively block (e.g., in a dose-dependent manner) the binding of an anti-C10orf54 antibody provided herein to a C10orf54 polypeptide (e.g., cell surface expressed or soluble C10orf54 ), a C10orf54 fragment or a C10orf54 epitope, and/or (2) that binds to a C10orf54 epitope that binds to an anti-C10orf54 antibody (eg, a humanized anti-C10orf54 antibody) provided herein. In other incarnations, this antibody competently blocks the binding (for example, in a dose -dependent way) of the monocomponal antibodies 5V, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 175A 321D, 141A, 51A, 353A, or 305A described herein (e.g., in Tables 12-33), or a humanized variant thereof with a C10orf54 polypeptide (e.g., cell surface expressed or soluble C10orf54), a C10orf54 fragment, or a C10orf54 epitope. In other embodiments, the antibody binds to the C10orf54 epitope, which binds to (e.g., is recognized by) monoclonal antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A described in this application (for example, in Tables 12-33), or a humanized version thereof (for example, with humanized antibodies to C10orf54).

In certain embodiments, anti-C10orf54 antibodies (e.g., humanized anti-C10orf54 antibodies) provided herein (e.g., antibodies 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A , 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3) are conjugated or recombinantly fused to a diagnostic agent, detection agent or therapeutic agent. In some aspects, the therapeutic agent is a chemotherapeutic agent (eg, a cytotoxic agent such as a cytotoxin). In some aspects, the detectable agent is a radioactive isotope, enzyme, fluorescent compound, bioluminescent compound, or chemiluminescent compound. In certain embodiments, the anti-C10orf54 antibodies provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 32 1D , 141A, 51A, 353A or 305A described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3) are conjugated to drugs in the form of antibody-drug conjugates (ADCs). In some aspects, the antibody-drug conjugate (ADC) has the formula A-L-CTX, where A is an antibody, L is a linker, and CTX is a cytotoxin.

In certain embodiments, compositions are provided containing an anti-C10orf54 antibody (eg, humanized anti-C10orf54 antibodies) described herein. In some embodiments, these compositions contain an antibody-drug conjugate, wherein the antibody is an anti-C10orf54 antibody as provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2 , VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3). Additionally, this application provides pharmaceutical compositions containing an anti-C10orf54 antibody, including the humanized anti-C10orf54 antibody provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2 , VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3).

In certain embodiments, the antibody provided herein binds to the first group of C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CCS (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC10 (SEQ ID NO: 1251), and does not bind to the second group of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248) and CC9 (SEQ ID NO: 1250).

In certain embodiments, the antibody provided herein binds to the first group of C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CCS (SEQ ID NO: 1246) and CC8 (SEQ ID NO: 1249), and does not bind to the second group of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251). In some aspects, such an antibody does not contain one or more CDR sequences selected from the group consisting of 30, 1099, 1104, 1105, 1110, 31, 1100, 1106, 1111, 1116, 32, 1101, 1107, 1112, 45, 1102 , 1108, 1113, 40, 1103, 1114, 41, 1109 and 1115.

In certain embodiments, the antibody provided herein binds to the first group of C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245) and CCS (SEQ ID NO: 1246), and does not bind to the second group of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC8 (SEQ ID NO: 1249), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251). In some aspects, such an antibody does not contain one or more CDR sequences selected from the group consisting of 36, 1081, 1086, 1087, 1092, 37, 1082, 1088, 1093, 1098, 38, 1083, 1089, 1094, 45, 1084, 1090, 1095, 46, 1085, 1096, 47, 1091 and 1097.

In certain embodiments, the antibody provided herein binds to the first group of C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CCS (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC9 (SEQ ID NO: 1250), and does not bind to the second group of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 ( SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251). In some aspects, such an antibody does not contain one or more CDR sequences selected from the group consisting of 33, 1117, 1122, 1123, 1128, 34, 1118, 1124, 1129, 1134, 35, 1119, 1125, 1130, 42, 1120, 1126, 1131, 43, 1121, 1132, 44, 1127 and 1133.

In certain embodiments, the antibody provided herein binds to the first group of C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC3 (SEQ ID NO: 1244), CC4 (SEQ ID NO: 1245), CCS (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC9 (SEQ ID NO: 1250), and does not bind to the second group of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248) and CC10 (SEQ ID NO: 1251).

In certain embodiments, the antibody provided herein binds to the first group of C10orf54 proteins or chimeric proteins designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CCS (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC10 (SEQ ID NO: 1251), and does not bind to the second group of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 ( SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251).

According to a third aspect, this application provides isolated nucleic acid molecules encoding the VH chain, VL chain, VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3 antibodies to C10orf54, which are described in this application (for example, antibodies 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 1A, 51A , 353A or 305A described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), in including humanized anti-C10orf54 antibodies that bind to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope. In certain embodiments, the nucleic acid molecule encodes the VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3 monobody antibodies 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A described in this application (for example, in Tables 12-33) or a humanized version thereof. In certain embodiments, the nucleic acid molecule further encodes VH FR1, VH FR2, VH FR3, VH FR4, VL FR1, VL FR2, VL FR3 and/or VL FR4 from a human germline immunoglobulin amino acid sequence or variant thereof. In addition, this application provides vectors and host cells containing nucleic acid molecules encoding an antibody to C10orf54 (for example, humanized antibodies to C10orf54), as well as methods for producing antibodies to C10orf54 by culturing the host cells proposed in this application under conditions which promote the production of antibodies to C10orf54.

In a fourth aspect, this application provides methods of treating, preventing, or alleviating a disease, disorder, or condition, including one or more symptoms of the disease, disorder, or condition, comprising administering a therapeutically effective amount of an anti-C10orf54 antibody as described herein (e.g., an anti-C10orf54 antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example , in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), including an antibody-drug conjugate (ADC), containing the antibody to C10orf54 proposed in this application (for example, 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, D, 141A, 51A, 353A or 305A described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), subject, resulting in the treatment, prevention or alleviation of a disease, disorder or condition, including one or more symptoms of the disease, disorder or condition. In some embodiments, anti-C10orf54 antibodies are humanized antibodies that bind to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope. In one embodiment, the disease, disorder, or condition is caused by or otherwise associated with C10orf54, including caused by or associated with C10orf54-expressing cells (eg, tumor cells, myeloid-derived suppressor cells (MDSCs), suppressive dendritic cells (suppressive dendritic cells) DC) and/or regulatory T cells (T _reg )). In certain embodiments, the disease is a cancer, such as leukemia, bladder cancer, skin cancer, colon cancer, breast cancer, liver cancer, kidney cancer, lung cancer, gastric cancer, pancreatic cancer, esophageal cancer, or fibrosarcoma. In one embodiment, the leukemia is acute myeloid leukemia (AML). In other embodiments, the disease is graft-versus-host disease (GVHD). Additional methods proposed include the use of an anti-C10orf54 antibody having C10orf54-binding activity in the case of C10orf54-expressing cells as provided herein (e.g., antibodies 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), for example, as an unconjugated antibody or an antibody conjugated (ADC), including for the inhibition and/or killing of C10orf54-expressing cells (for example, with antitumor activity to mediate the antitumor effect). In certain embodiments, anti-C10orf54 antibodies, including ADCs containing anti-C10orf54 antibodies provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A , 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3 , VL CDR1, VL CDR2 and/or VL CDR3) inhibit C10orf54-mediated T cell suppressive activity (eg, allowing an effective antitumor immune response). In certain embodiments, the anti-C10orf54 antibodies provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 32 1D , 141A, 51A, 353A or 305A described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3) directly kill C10orf54-expressing cells (eg, C10orf54-bearing tumor cells, myeloid-derived suppressor cells (MDSCs), suppressive dendritic cells (suppressive DCs), and/or regulatory T cells (T _reg )), e.g. , through the manifestation of antibody-dependent cellular cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC). In certain embodiments, antibody-drug conjugates (ADCs) containing anti-C10orf54 antibodies provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3) directly kill C10orf54-expressing cells, including by binding to C10orf54-expressing cells (eg, tumor cells, myeloid suppressor cells (MDSC), suppressive dendritic cells (suppressive action of DC) and/or regulatory T cells (T _reg )), for example, allowing internalization of a cytotoxic drug. In certain embodiments, anti-C10orf54 antibodies provided herein, or antibody-drug conjugates (ADCs) containing anti-C10orf54 antibodies provided herein, are used in methods of treating cancers (e.g., bladder, breast, colon cancer). colon, connective tissue, rectal, gastric, esophageal, lung, larynx, kidney, oral, ovarian or prostate cancers or sarcoma, melanoma, glioma, lymphoma or leukemia) or myeloid-derived suppressor cell (MDSC) tumors (eg , colon cancer, breast carcinoma, fibrosarcoma, thymoma, lung cancer, renal cell carcinoma, mesothelioma, glioma, lymphoma, sarcoma, prostate carcinoma, sarcoma or head and neck carcinoma). In any of the above embodiments, the anti-C10orf54 antibody may be a humanized anti-C10orf54 antibody as provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), which binds to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope.

According to a fifth aspect, this application provides methods for inhibiting cell growth and/or killing cells expressing C10orf54 on their surface, comprising contacting the cells with an effective amount of an anti-C10orf54 antibody or antibody-drug conjugates containing an anti-C10orf54 antibody as provided herein. (for example, 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 30 5A described in this application (for example, in Tables 12-33) containing VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3). In one embodiment, the cell is a regulatory T cell (eg, a CD4 ⁺ Foxp3 ⁺ regulatory T cell). In certain embodiments, the present invention provides a method of inhibiting the growth of an inflammatory tumor in a subject, comprising administering an effective amount of anti-C10orf54 antibodies, including ADCs containing anti-C10orf54 antibodies provided herein (e.g., 5B, 46A, 97A, 128A, 146C , 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3). In other embodiments, the cell is a myeloid suppressor cell (eg, CD11b ⁺ or CD11b ^high myeloid suppressor cell) or a suppressive dendritic cell (eg, CD11b ⁺ or CD11b ^high dendritic cell). In other embodiments, the cell is a cancerous or precancerous cell. Additional methods proposed include the use of an anti-C10orf54 antibody having C10orf54-binding activity in the case of C10orf54-expressing cells as provided herein (e.g., antibodies 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), for example, as an unconjugated antibody or an antibody conjugated (ADC), including for the inhibition and/or killing of C10orf54-expressing cells (for example, with antitumor activity to mediate the antitumor effect). In certain embodiments, anti-C10orf54 antibodies, including ADCs containing anti-C10orf54 antibodies provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A , 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3 , VL CDR1, VL CDR2 and/or VL CDR3) inhibit C10orf54-mediated T cell suppressive activity (eg, allowing an effective antitumor immune response). In certain embodiments, the anti-C10orf54 antibodies provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 32 1D , 141A, 51A, 353A or 305A described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3) directly kill C10orf54-expressing cells (eg, C10orf54-bearing tumor cells, myeloid-derived suppressor cells (MDSCs), suppressive dendritic cells (suppressive DCs), and/or regulatory T cells (T _reg )), e.g. , through the manifestation of antibody-dependent cellular cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC). In certain embodiments, antibody-drug conjugates (ADCs) containing anti-C10orf54 antibodies provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3) directly kill C10orf54-expressing cells, including by binding to C10orf54-expressing cells (eg, tumor cells, myeloid suppressor cells (MDSC), suppressive dendritic cells (suppressive action of DC) and/or regulatory T cells (T _reg )), for example, allowing internalization of a cytotoxic drug. In any of the above embodiments, the anti-C10orf54 antibody may be a humanized anti-C10orf54 antibody as provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), which binds to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope.

According to a sixth aspect, this application provides methods for modulating an immune response in a subject, comprising administering an effective amount of an anti-C10orf54 antibody (e.g., a humanized anti-C10orf54 antibody) provided herein (e.g., antibodies 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain , VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), subject. In one embodiment, modulation includes increasing T cell activation. In another embodiment, the modulation includes enhancing T cell proliferation. In another embodiment, modulation includes increasing the production of cytokines.

According to a seventh aspect, this application provides methods for detecting C10orf54 in a sample, comprising contacting the sample with an anti-C10orf54 antibody (e.g., a humanized anti-C10orf54 antibody) provided herein (e.g., antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing V H -domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), such as an antibody that contains a detectable agent. In certain embodiments, the sample contains a cell expressing C10orf54 on its surface.

In an eighth aspect, this application provides methods for treating cancer diseases comprising administering to a subject an anti-C10orf54 antibody (e.g., a humanized anti-C10orf54 antibody) or an antibody-drug conjugate (ADC) containing an anti-C10orf54 antibody (e.g., an ADC of the formula AL-CTX, wherein A is an antibody, L is a linker, and CTX is a cytotoxic agent) provided herein (e.g., antibodies 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), in a therapeutically effective amount, including an amount effective to kill a C10orf54-expressing cell (eg, a tumor cell, a myeloid-derived suppressor cell (MDSC) that has a dendritic cell suppressive effect (having a suppressive effect on DC) and/or regulatory T cells (T _reg )). In some embodiments, the cancer is acute myeloid leukemia (AML). In any of the above embodiments, the anti-C10orf54 antibody may be a humanized anti-C10orf54 antibody as provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), which binds to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope.

In a ninth aspect, this application provides methods for killing C10orf54-expressing cells (e.g., tumor cells, myeloid-derived suppressor cells (MDSC), dendritic cell suppressive cells (DC suppressive cells), and/or T regulatory cells (T _reg )), comprising contacting a C10orf54-expressing cell (eg, a tumor cell, a myeloid suppressor cell (MDSC), a suppressive dendritic cell (DC suppressive), and/or a regulatory T cell (T _reg )) with an anti-C10orf54 antibody or conjugate an antibody-drug (ADC) containing an anti-C10orf54 antibody (e.g., an ADC of the formula AL-CTX, where A is an antibody, L is a linker, and CTX is a cytotoxic agent) provided herein (e.g., antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33) containing VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), in an amount effective to kill a given cell (for example, a tumor cell, myeloid suppressor cell (MDSC), which has a suppressive effect on a dendritic cell (which has a suppressive effect on DC) and/or a regulatory T cell (T _reg )). In some embodiments, the tumor cell is an AML cell. In any of the above embodiments, the anti-C10orf54 antibody may be a humanized anti-C10orf54 antibody as provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3), which binds to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope.

According to a tenth aspect, this application provides a kit containing an anti-C10orf54 antibody (e.g., a humanized anti-C10orf54 antibody) that binds to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33 ), containing VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3). In some embodiments, the kits contain an antibody-drug conjugate (ADC), wherein the antibody is an anti-C10orf54 antibody (e.g., a humanized anti-C10orf54 antibody) as provided herein (e.g., 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, described in this application (for example, in Tables 12-33), containing a VH domain , VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3).

TERMINOLOGY

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. All patents, applications, published applications and other publications are incorporated by reference in their entirety. In the event that multiple definitions exist for a term used herein, those given in this section shall prevail unless otherwise noted.

The term "about" or "approximately" means within 20%, such as within 10%, or within 5% (or 1% or less) of a given value or range.

As used herein, the term “administer” or “administration” refers to the act of injecting or otherwise physically delivering a substance that is outside the body (for example, the anti-C10orf54 antibody of this invention) to a patient, such as mucosal, intradermal, intravenous, intramuscular delivery , and/or any other method of physical delivery set forth herein or known in the art. When a disease or symptom thereof is being treated, administration of the substance is usually carried out after the onset of the disease or the onset of its symptoms. When preventing a disease or its symptoms, administration of the substance is usually carried out before the onset of the disease or the onset of its symptoms.

As used herein, the term “C10orf54 agonist” refers to a molecule that is capable of activating or otherwise enhancing one or more biological activities of C10orf54, for example, in a cell expressing C10orf54, or in a cell expressing a C10orf54 ligand, such as a C10orf54 receptor. In some embodiments, a C10orf54 agonist (e.g., an agonist antibody provided herein) may act, for example, by activating or otherwise enhancing the activation and/or cellular signaling pathways of a cell expressing C10orf54 or a C10orf54 receptor, thereby enhancing the C10orf54-mediated biological activity of that cell. cells compared to C10orf54-mediated biological activity in the absence of agonist. In certain embodiments, the antibodies provided herein are anti-C10orf54 agonistic antibodies.

The term "alkyl" as used herein means a straight, branched or cyclic (in which case it will also be known as "cycloalkyl") hydrocarbon containing 1-10 carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, 3-methylhexyl, 2,2 -dimethylpentyl, 2,3-dimethylhexyl, n-heptyl, n-octyl, n-nonyl and n-decyl. In certain embodiments, alkyl groups are optionally substituted.

The term "C ₁ - ₆ alkyl" as used herein means a straight, branched or cyclic (in which case it will also be known as "cycloalkyl") hydrocarbon containing 1-6 carbon atoms.

The term "C ₁ - ₃ alkyl" as used herein means a straight or branched hydrocarbon containing 1-3 carbon atoms.

The term "alkenyl" as used herein means a straight, branched or cyclic (in which case it will also be known as "cycloalkenyl") hydrocarbon containing 2-10 carbon atoms and containing at least one carbon-carbon double bond formed resulting from the removal of two hydrogen atoms. In some embodiments, depending on the structure, the alkenyl group is a monoradical or diradical (eg, an alkenylene group). In some embodiments, alkenyl groups are optionally substituted. Examples of alkenyl include, but are not limited to, ethenyl, 2-propenyl, 2-methyl-2-propenyl, 3-butenyl, 4-pentenyl, 5-hexenyl, 2-heptenyl, and 2-methyl-1-heptenyl. In certain embodiments, alkenyl groups are optionally substituted.

The term "C ₂ - ₆ alkenyl" as used herein means a straight, branched or cyclic (in which case it will also be known as "cycloalkyl") hydrocarbon containing 2-6 carbon atoms and at least one carbon-carbon double a bond formed by the removal of two hydrogen atoms.

The term "alkoxy" as used herein means an alkyl group, as defined herein, attached to the parent molecular moiety via an oxygen atom. Examples of alkoxy include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, t-butoxy, pentyloxy and hexyloxy.

An "amino acid" (or AA) or amino acid residue includes, but is not limited to, the 20 naturally occurring amino acids, usually designated by three-letter symbols, and also includes 4-hydroxyproline, hydroxylysine, desmosine, isodesmosine, 3-methylhistidine, norvaline, beta-alanine, gamma -aminobutyric acid, homocysteine, homoserine, ornithine and methionine sulfone. "Amino acid residue" as used herein also includes the corresponding N-methylamino acids such as -N(CH ₃ )CH ₂ C(O)O-, -NHC(O)CH ₂ CH ₂ CH(NHCH ₃ )C(O )O-, etc. Amino acids, dipeptides, tripeptides, oligomers and polypeptides, referred to herein as -(AA) _r -, may include corresponding non-N-alkylated amino acids and peptides (such as non-N-methylated amino acids in peptides), as well as a mixture non-N-alkylated amino acids and N-alkylated amino acid peptides.

An "antibody-drug conjugate" or "ADC" is an antibody that is conjugated to one or more cytotoxins through one or more linkers. An antibody-drug conjugate (ADC) may have the formula A-L-CTX, where A is an antibody, L is a linker, and CTX is a cytotoxin.

In the context of a polypeptide, the term "analog" as used herein refers to a polypeptide that has a function similar or identical to the function of a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody, but does not necessarily contain a sequence similar or identical to the amino acid sequence of a C10orf54 polypeptide. a fragment of a C10orf54 polypeptide or an anti-C10orf54 antibody, or does not necessarily have a structure similar or identical to the structure of a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide or an anti-C10orf54 antibody. A polypeptide having a similar amino acid sequence refers to a polypeptide that satisfies at least one of the following: (a) a polypeptide having an amino acid sequence that is at least 30%, at least 35%, at least 40 %, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75% is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the amino acid sequence of the C10orf54 polypeptide (e.g., SEQ ID NO: 1079), a fragment of a C10orf54 polypeptide or an anti-C10orf54 antibody described herein; (b) a polypeptide encoded by a nucleotide sequence that hybridizes under stringent conditions to a nucleotide sequence encoding a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody (or a VH or VL region thereof) described herein and consisting of at least 5 amino acid residues, at least 10 amino acid residues, at least 15 amino acid residues, at least 20 amino acid residues, at least 25 amino acid residues, at least 40 amino acid residues, at least 50 amino acid residues residues of at least 60 amino acid residues, at least 70 amino acid residues, at least 80 amino acid residues, at least 90 amino acid residues, at least 100 amino acid residues, at least 125 amino acid residues, or of at least 150 amino acid residues (see, for example, Sambrook et al, (2001) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Maniatis et al, (1982) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Press, Cold Spring Harbor, NY); and (c) a polypeptide encoded by a nucleotide sequence that is at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90 % is at least 95% or at least 99% identical to the nucleotide sequence encoding a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody (or a VH or VL region thereof) described in this application. A polypeptide with a structure similar to that of a C10orf54 polypeptide, a C10orf54 polypeptide fragment, or an anti-C10orf54 antibody described herein refers to a polypeptide that has a secondary, tertiary, or quaternary structure similar to that of a C10orf54 polypeptide, a C10orf54 fragment, or an anti-C10orf54 antibody described herein application. The structure of a polypeptide can be determined by methods known to those skilled in the art, including, but not limited to, X-ray crystallography, nuclear magnetic resonance, and electron microscopy of crystallographic samples.

As used herein, the term "antagonist" or "inhibitor" of C10orf54 refers to a molecule that is capable of inhibiting or otherwise reducing one or more biological activities of C10orf54, for example, in a cell expressing C10orf54 or in a cell expressing a C10orf54 ligand such as a receptor C10orf54. In some embodiments, a C10orf54 antagonist (e.g., an antagonist antibody provided herein) may act, for example, by inhibiting or otherwise attenuating activation and/or cellular signaling pathways in a cell expressing C10orf54 or a C10orf54 receptor, thereby inhibiting C10orf54-mediated biological activity cells compared to C10orf54-mediated biological activity in the absence of antagonist. In certain embodiments, the antibodies provided herein are antagonistic antibodies to C10orf54.

The terms "antibody" and "immunoglobulin" or "Ig" are used interchangeably herein and are intended to include a B cell polypeptide product belonging to the immunoglobulin class of polypeptides that is capable of binding to a specific molecular antigen and is composed of two identical pairs of polypeptide chains, each pair having one heavy chain (about 50-70 kilodaltons (kDa)) and one light chain (about 25 kDa), and each amino-terminal portion of each chain includes a variable region containing from about 100 to about 130 or more amino acids, and each carboxy-terminal portion of each chain includes a constant region (see Borrebaeck (ed.) (1995) Antibody Engineering. Second Ed., Oxford University Press.; Kuby (1997) Immunology. Third Ed., W.H. Freeman and Company, New York). In specific embodiments, the specific molecular antigen that can bind to the antibody provided herein includes a target C10orf54 polypeptide, fragment, or epitope.

Antibodies also include, but are not limited to, synthetic antibodies, monoclonal antibodies, recombinantly produced antibodies, multispecific antibodies (including bispecific antibodies), human antibodies, humanized antibodies, camel antibodies, chimeric antibodies, intraantibodies, anti-idiotypic (anti-Id) antibodies and functional fragments of any of the above, which refer to a portion of an antibody heavy or light chain polypeptide that retains some or all of the binding activity of the antibody from which the fragment was derived. Non-limiting examples of functional fragments include single chain Fv (scFv) (including, for example, monospecific, bispecific, etc.), Fab fragments, F(ab') fragments, F(ab) ₂ fragments, F(ab') ₂ Fv disulfide bonded fragments (sdFv), Fd fragments, Fv fragments, diabody, tribody, tetrabody and minibody. In particular, the antibodies provided herein include immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, e.g., antigen binding domains, or molecules containing an antigen binding site that binds to the C10orf54 antigen (e.g., containing one or more complementarity determining regions (CDRs) antibodies to C10orf54). Descriptions of such antibody fragments can be found, for example, in Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York (1989); Myers (ed.), Molec. Biology and Biotechnology: A Comprehensive Desk Reference, New York: VCH Publisher, Inc.; Huston et al., Cell Biophysics, 22:189-224 (1993); Pluckthun and Skerra, Meth. Enzymol., 178: 497-515 (1989) and in Day ED, Advanced Immunochemistrv, Second Ed., Wiley-Liss, Inc., New York, NY (1990). The antibodies provided herein may be any type of immunoglobulin molecule (e.g., IgG, IgE, IgM, IgD, IgA, and IgY), any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2), or any subclass (eg IgG2a and IgG2b). Antibodies to C10orf54 proposed in this application can be agonistic antibodies or antagonistic antibodies.

The terms “antibodies that specifically bind to C10orf54,” “antibodies that specifically bind to a C10orf54 epitope,” “anti-C10orf54 antibodies,” and similar terms are also used interchangeably herein and refer to antibodies that specifically bind to a C10orf54 polypeptide, e.g. antigen or epitope C10orf54. Such antibodies include humanized antibodies. An antibody that specifically binds to the C10orf54 antigen can cross-react with related antigens. In certain embodiments, an antibody that specifically binds to the C10orf54 antigen does not cross-react with other antigens. An antibody that specifically binds to the C10orf54 antigen can be identified, for example, using immunoassays, BIAcore, or other methods known to those skilled in the art. An antibody binds specifically to a C10orf54 antigen when it binds to a C10orf54 antigen with higher affinity than any cross-reacting antigen, as determined using experimental methods such as radioimmunoassays (RIAs) and enzyme-linked immunosorbent assays (ELISAs). Typically, the signal in a specific or selective interaction will be at least twice the background signal or noise, and more typically more than 10 times the background. See, for example, Paul, ed., 1989, Fundamental Immunology, Second Edition, Raven Press, New York, pages 332-336 for a discussion regarding antibody specificity. In certain embodiments, an antibody “that binds to” an antigen of interest is an antibody that binds to the antigen with sufficient affinity to make the antibody useful as a diagnostic and/or therapeutic agent for targeting a cell or tissue expressing given antigen, and did not cross-react significantly with other proteins. In such embodiments, the extent of binding of the antibody to the "off-target" protein will be less than about 10% of the binding of the antibody to its particular target protein, as determined by fluorescence-activated cell sorting (FACS) or radioimmunoprecipitation (RIA) analysis. . With respect to the binding of an antibody to a target molecule, the term "specific binding" or "specifically binds to" a particular polypeptide or epitope or is "specific to" a particular polypeptide or epitope on a particular target polypeptide means binding that is different from non-specific when measured interactions. Specific binding can be measured, for example, by determining the binding of a molecule compared to the binding of a control molecule, which is typically a molecule of similar structure that has no binding activity. For example, specific binding can be determined using competition with a control molecule that is similar to the target, for example, in the presence of an excess of unlabeled target. In this case, specific binding is indicated by the fact that binding of the labeled target to the probe is competitively inhibited by an excess of unlabeled target. The term "specific binding" or "specifically binds to" a particular polypeptide or epitope or is "specific to" a particular polypeptide or epitope on a particular target polypeptide, as used herein, can be applied, for example, to a molecule having a Kd for the target , being at least about 10 ^-4 M, alternatively at least about 10 ^-5 M, alternatively at least about 10 ^-6 M, alternatively at least about 10 ^-7 M, alternatively at least about 10 ^-8 M, alternatively at least about 10 ^-9 M, alternatively at least about 10 ^-10 M, alternatively at least about 10 ^-11 M, alternatively at least about 10 ^-12 M or less . In one embodiment, the term “specific binding” refers to binding where a molecule binds to a particular polypeptide or epitope of a particular polypeptide without substantially binding to any other polypeptide or epitope of a polypeptide. In certain embodiments, an antibody that binds to C10orf54 has a dissociation constant (Kd) of no more than 1 μM, no more than 100 nM, no more than 10 nM, no more than 1 nM, or no more than 0.1 nM. In certain embodiments, an anti-C10orf54 antibody binds to a C10orf54 epitope that is conserved among C10orf54 from different species.

The term “anti-C10orf54 antibody” or “antibody that binds to C10orf54” refers to an antibody capable of binding to C10orf54, including, for example, an antibody with sufficient affinity to make the antibody useful as a diagnostic and/or therapeutic agent with a targeted effect on C10orf54. Such antibodies include humanized antibodies. Preferably, the extent of binding of the anti-C10orf54 antibody to an unrelated non-C10orf54 protein is less than about 10% of the binding of the antibody to C10orf54 as measured, for example, in a fluorescence-activated cell sorting (FACS) or radioimmunoassay (RIA) assay. . The definition of an antibody that "specifically binds to" or is "specific to" C10orf54 is given above. In certain embodiments, an antibody that binds to C10orf54 has a dissociation constant (Kd) of less than 1 μM, less than 100 nM, less than 10 nM, less than 1 nM, or less than 0.1 nM. In certain embodiments, an anti-C10orf54 antibody binds to a C10orf54 epitope that is conserved among C10orf54 from different species.

The term "antigen" refers to a predetermined antigen to which an antibody can selectively bind. The target antigen may be a polypeptide, carbohydrate, nucleic acid, lipid, hapten, or other natural or synthetic compound. In specific embodiments, the target antigen is a polypeptide.

The term “antigen-binding fragment,” “antigen-binding domain,” “antigen-binding region,” and similar terms refer to that portion of an antibody that contains amino acid residues that interact with an antigen and confer upon the binding agent its inherent specificity and affinity for that antigen (e.g. , to complementarity determining regions (CDRs)).

The terms “binding” or “linking” as used herein refer to the interaction between molecules to form a complex. The interactions may be, for example, non-covalent interactions, including hydrogen bonds, ionic bonds, hydrophobic interactions and/or van der Waals interactions. A complex can also be formed by the binding of two or more molecules held together by covalent or non-covalent bonds, interactions or forces. The strength of all noncovalent interactions between one antigen-binding site on an antibody and one epitope on a target molecule, such as C10orf54, represents the affinity of the antibody or functional fragment for that epitope. The ratio of the rate constant of association (k ₁ ) to the rate constant of dissociation (k _-1 ) of an antibody with a monovalent antigen (k ₁ /k _-1 ) is the association constant K, which is a measure of affinity. The value of K varies for different antibody-antigen complexes and depends on both the constants k ₁ and k _-1 . The association constant K for the antibody provided herein can be determined using any method described herein or any other method well known to those skilled in the art. Affinity for a single binding site does not always reflect the true strength of the interaction between antibody and antigen. When complex antigens containing multiple, repetitive antigenic determinants, such as the multivalent C10orf54, come into contact with antibodies containing multiple binding sites, the interaction of the antibody with the antigen at one site will increase the likelihood of interaction at a second site. The strength of such multiple interactions between a multivalent antibody and an antigen is called avidity. The avidity of an antibody may be a more appropriate measure of its binding ability than the affinity of its individual binding sites. For example, high avidity can compensate for low affinity, as is sometimes observed for pentameric IgM antibodies, which may have lower affinity than IgG, but the higher avidity of IgM, resulting from their multivalency, allows them to bind antigen efficiently.

The term "C10orf54" or "C10orf54 polypeptide" and similar terms refer to a polypeptide ("polypeptide", "peptide" and "protein" are used interchangeably herein) encoded by a gene from open reading frame 54 on human chromosome 10 (C10orf54) that also known in the art as B7-H5, platelet receptor Gi24, GI24, stress-inducible secreted protein 1, SISP1, and PP2135, containing the amino acid sequence:

and related polypeptides, including their SNP (single nucleotide polymorphism) variants. The C10orf54 polypeptide is shown or suggested to contain several different regions within the amino acid sequence, including: a signal sequence (residues 1-32; see Zhang et al., Protein Sci., 13: 2819-2824 (2004)); immunoglobulin domain - IgV-like (residues 33-162); and a transmembrane region (residues 195-215). The mature C10orf54 protein includes amino acid residues 33-311 of SEQ ID NO: 1079. The extracellular domain of the C10orf54 protein includes amino acid residues 33-194 of SEQ ID NO: 1079. Related polypeptides include allelic variants (eg, SNP variants); splice variants; fragments; derivatives; variants with substitutions, deletions and insertions; fusion polypeptides (eg, chimeric proteins); and cross-species homologs, preferably those that retain C10orf54 activity and/or are sufficient to generate an immune response to C10orf54. As will be apparent to those skilled in the art, the anti-C10orf54 antibody provided herein can bind to a polypeptide, polypeptide fragment, antigen, and/or epitope of C10orf54, since the epitope is part of a larger antigen that is part of a larger polypeptide fragment that , in turn, is part of a larger polypeptide. C10orf54 can be in native or denatured form. The C10orf54 polypeptides described herein can be isolated from various sources, for example, from different types of human tissue or other source, or obtained by recombinant or synthetic methods. A “native sequence C10orf54 polypeptide” is a polypeptide having the same amino acid sequence as the corresponding naturally occurring C10orf54 polypeptide. Such native sequence C10orf54 polypeptides can be isolated from natural sources or can be produced by recombinant or synthetic methods. The term “native sequence C10orf54 polypeptide” specifically includes naturally occurring truncated or secreted forms of a particular C10orf54 polypeptide (e.g., extracellular domain sequence), naturally occurring variant forms (e.g., forms resulting from alternative splicing), and naturally occurring allelic variants of the polypeptide.

The cDNA nucleic acid sequence encoding the C10orf54 polypeptide contains:

Orthologues of the C10orf54 polypeptide are also well known in the art. For example, the murine orthologue of the C10orf54 polypeptide is a V-region immunoglobulin suppressor of T cell activation (VISTA) (also known as PD-L3, PD-1H, PD-XL, Pro1412, and UNQ730) that has approximately 70% sequence identity sequences of this polypeptide in humans. Orthologs of C10orf54 can also be found in other organisms, including chimpanzee, cow, rat, and zebrafish.

The expression "C10orf54-expressing cell", "cell expressing C10orf54" or its grammatical equivalent refers to a cell that expresses endogenous or transfected C10orf54 on the cell surface. C10orf54-expressing cells include C10orf54-bearing tumor cells, regulatory tumor cells (eg, CD4 ⁺ Foxp3 ⁺ regulatory T cells), myeloid suppressor cells (eg, CD11b ⁺ or CD11b ^high myeloid suppressor cells), and/or suppressive dendritic cells (eg CD11b ⁺ or CD11b ^high dendritic cells). A cell expressing C10orf54 produces significant levels of C10orf54 on its surface so that anti-C10orf54 antibody can bind to it. In one aspect, such binding may have a therapeutic effect against cancer. A cell that "overexpresses" C10orf54 is a cell that has significantly higher levels of C10orf54 on its cell surface compared to a cell of the same tissue type that is known to express C10orf54. Such overexpression may be due to gene amplification or increased transcription or translation. Overexpression of C10orf54 can be determined in a diagnostic or prognostic assay by assessing increased levels of C10orf54 protein present on the cell surface (eg, using immunohistochemical analysis; FACS analysis). Alternatively or in addition, levels of C10orf54-encoding nucleic acid or messenger ribonucleic acid (mRNA) in a cell can be measured, for example, using fluorescence in situ hybridization (FISH; see application W098/45479 published in October 1998), Southern blotting, Northern blotting or polymerase chain reaction (PCR), such as quantitative real-time PCR (RT-PCR). In addition to the assays described above, various in vivo assays are available to skilled practitioners. For example, cells of a patient's body can be exposed to an antibody that can be labeled with a detectable agent, and the binding of the antibody to the patient's cells can be assessed, for example, by external scanning for radioactivity or by analyzing a biopsy taken from a patient previously exposed to the antibody. A C10orf54-expressing tumor cell includes, but is not limited to, acute myeloid leukemia (AML) tumor cells.

The terms "C10orf54-mediated disease", "C10orf54-mediated disorder" and "C10orf54-mediated condition" are used interchangeably and refer to any disease, disorder or condition that is caused in whole or in part by or that results from the presence of C10orf54. Such diseases, disorders or conditions include those caused by or otherwise associated with C10orf54, including those caused by or associated with C10orf54-expressing cells (eg, tumor cells, myeloid suppressor cells (MDSCs), suppressive dendritic cells (having suppressive effect of DC) and/or regulatory T cells (T _reg )). In certain embodiments, C10orf54 is aberrantly (eg, highly) expressed on the cell surface. In some embodiments, C10orf54 may be aberrantly activated on a particular cell type. In other embodiments, normal, aberrant, or excessive cell signaling is due to the binding of C10orf54 to a C10orf54 ligand that can bind or otherwise interact with C10orf54.

The terms "cell proliferation disorder" and "proliferative disorder" refer to disorders that are associated with some level of abnormal cell proliferation. In one embodiment, the disorder of cell proliferation is a tumor or cancer. The term "tumor" as used herein refers to any neoplastic cell growth and proliferation, whether malignant or benign, and any precancerous or cancerous cells and tissues. The terms “cancer,” “cancerous,” “cellular proliferation disorder,” “proliferative disorder,” and “tumor” are not mutually exclusive as defined herein. The terms "cancer" and "cancerous" refer to or describe a physiological condition in mammals that is typically characterized by unregulated cell growth. Examples of cancer include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma and leukemia or lymphocytic leukemia. More specific examples of such cancers include squamous cell carcinoma (eg, squamous cell carcinoma of epithelial origin), lung cancer, including small cell lung cancer, non-small cell lung cancer, adenocarcinoma of the lung and squamous cell carcinoma of the lung, peritoneal cancer, hepatocellular carcinoma, gastric cancer, or stomach, including gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, oral cancer, liver cancer, bladder cancer, urinary tract cancer, hepatoma, breast cancer, colon cancer, cancer rectal cancer, colorectal cancer, endometrial cancer or uterine cancer, salivary gland cancer, kidney cancer or renal cell cancer, prostate cancer, vulvar cancer, thyroid cancer, hepatic carcinoma, anal cancer, penile cancer, melanoma, multiple myeloma and B -cell lymphoma, brain cancer, skin cancer, esophageal cancer, as well as head and neck cancer and metastases associated with these types of cancer.

The term "carrier" refers to a diluent, adjuvant (eg, Freund's adjuvant (complete and incomplete)), excipient or excipient with which the therapeutic agent is administered. Such pharmaceutical carriers may be sterile liquids such as water and oils, including hydrocarbon-derived liquids, animal, vegetable or synthetic liquids such as peanut oil, soybean oil, mineral oil, sesame oil and the like. Water is a typical carrier when the pharmaceutical composition is administered intravenously. Saline solutions and aqueous solutions of dextrose and glycerol can also be used as liquid carriers, in particular for injection solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, skim milk powder, glycerin, propylene glycol, water, ethanol and the like. If desired, the composition may also contain minor amounts of wetting or emulsifying agents or pH maintaining agents. These compositions may take the form of solutions, suspensions, emulsions, tablets, pills, capsules, powders, sustained release formulations, and the like. The oral composition may include standard carriers such as mannitol, lactose, starch, magnesium stearate, sodium saccharin, cellulose, magnesium carbonate, etc. pharmaceutical grade. Examples of suitable pharmaceutical carriers are described in Pharmaceutical Sciences (1990) Mack Publishing Co., Easton, PA. Such compositions will contain a prophylactically or therapeutically effective amount of the antibody, for example, in isolated or purified form, together with a suitable amount of carrier so as to provide a form for proper administration to a patient. The composition must be appropriate for the route of administration.

The term "chemical group" as used herein refers to two or more atoms bonded together as a unit to form part of a molecule.

A "chemotherapeutic agent" is a chemical agent (eg, a compound or drug) useful for treating cancer, regardless of the mechanism of action. Chemotherapeutic agents include compounds used in targeted therapies and conventional chemotherapy. Examples of chemotherapeutic agents include, but are not limited to, alkylating agents such as thiotepa and CYTOXAN® cyclophosphamide; alkylsulfonates such as busulfan, improsulfan and piposulfan; aziridines such as benzodopa, carboquone, meturedopa and uredopa; ethyleneimines and methylmelamines, including altretamine, triethylenemelamine, triethylenephosphoramide, triethylenethiophosphoramide and trimethylmelamine; acetogenins (in particular bullatacin and bullatacinone); delta-9-tetrahydrocannabinol (dronabinol, MARINOL®); beta-lapachone; lapachol; colchicines; betulinic acid; camptothecin (including synthetic analogue of topotecan (HYCAMTIN®), CPT-11 (irinotecan, CAM PTOS AR®), acetyl camptothecin, scopolectin and 9-aminocamptothecin); bryostatin; kallistatin; CC-1065 (including its synthetic analogues adozelesin, carzelesin and bizelesin); podophyllotoxin; podophyllic acid; teniposide; cryptophycins (particularly cryptophycin 1 and cryptophycin 8); dolastatin; duocarmycin (including synthetic analogues KW-2189 and CB1-TM1); eleutherobin; pancratistatin; sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chlornaphasine, chlorphosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembiquine, phenesterine, prednimustine, trofosfamide, uracil mustard; nitrosoureas such as carmustine, chlorosotocin, fotemustine, lomustine, nimustine and ranimustine; antibiotics such as enediyne antibiotics (eg, calicheamicin, in particular calicheamicin-gamma II and calicheamicin-omega II (see, for example, Angew. Chem. Intl. Ed. Engl., 33: 183-186 (1994)); dinemycin, including dinemycin A; as well as the neocarcinostatin chromophore and related chromophores of chromoproteins - enediin antibiotics), aclacinomysins, actinomycin, autramycin, azaserin, bleomycins, cactinomycin, carabicin, carminomycin, carzinophyllin, chromomycins, dactinomycin, daunorubicin, detorubicin, 6 -diazo-5-oxo-L-norleucine, ADRIAMYCIN®, doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, ezorubicin, idarubicin, marcellomycin, mitomycins such as mitomycin C , mycophenolic acid, nogalamycin, olivomycins, peplomycin, porfiromycin, puromycin, quelamycin, rhodorubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; antimetabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogs such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogues such as fludarabine, 6-mercaptopurine, thiamiprin, thioguanine; pyrimidine analogues such as ancytabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocytabine, floxuridine; androgens such as calusterone, dromostanolone propionate, epithiostanol, mepithiostane, testolactone; drugs that suppress adrenal function, such as aminoglutethimide, mitotane, trilostane; a folic acid compensator such as folinic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demecolcine; diaziquon; elfornitine; elliptinium acetate; epothilone; etoglucide; gallium nitrate; hydroxyurea; lentinan; lonidamine; maytansinoids such as maytansine and ansamitocins; mitoguazone; mitoxantrone; mopidanmol; nitraerin; pentostatin; phenomet; pirarubicin; losoxantrone; 2-ethylhydrazide; procarbazine; PSK® polysaccharide complex (JHS Natural Products, Eugene, Oreg.); razoxane; rhizoxin; sisofiran; spirogermanium; tenuazonic acid; triaziquon; 2,2',2''-trichlorotriethylamine; trichothecenes (particularly T-2 toxin, verracurine A, roridin A and anguidine); urethane; vindesine (ELDISINE®, FILDESIN®); dacarbazine; mannomustin; mitobronitol; mitolactol; pipobromance; gacytosine; arabinoside ("Ara-C"); thiotepa; taxoids, such as paclitaxel TAXOL® (Bristol-Myers Squibb Oncology, Princeton, N.J.), the cremophore-free albumin-bound nanoparticle formulation of paclitaxel ABRAXANE™ (American Pharmaceutical Partners, Schaumberg, IL.), and docetaxel TAXOTERE® (Rhone -Poulenc Rorer, Antony, France); chlorambucil; gemcitabine (GEMZAR®); 6-thioguanine; mercaptopurine; methotrexate; platinum analogues such as cisplatin and carboplatin; vinblastine (VELBAN®); platinum; etoposide (VP-16); ifosfamide; mitoxantrone; vincristine (ONCOVIN®); oxaliplatin; leucovorin; vinorelbine (NAVELBINE®); Novantrone; edatrexate; daunomycin; aminopterin; ibandronate; topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such as retinoic acid; capecitabine (XELODA®); and pharmaceutically acceptable salts, acids or derivatives of any of the above compounds, as well as combinations of two or more of the above compounds, such as CHOP, the short name for combination therapy with cyclophosphamide, doxorubicin, vincristine and prednisolone, and FOLFOX, the short name for the regimen treatment with oxaliplatin (ELOXATIN™) in combination with 5-FU and leucovorin. Additional chemotherapeutic agents include cytotoxic agents useful in antibody-drug conjugates, such as maytansinoids (DM1 and DM4, for example) and auristatins (MMAE and MMAF, for example).

Also included in the definition of a chemotherapeutic agent are: (1) antihormonal agents that act by regulating or inhibiting the effects of hormones on tumors, such as antiestrogens and selective estrogen receptor modulators (SERMs), including, for example, tamoxifen (including NOLVADEX®; tamoxifen citrate), raloxifene, droloxifene, 4-hydroxytamoxifene, trioxifene, keoxifene, LY 117018, onapristone and FARESTON® (toremifene citrate); (2) aromatase inhibitors, which inhibit the aromatase enzyme that regulates estrogen production in the adrenal glands, such as, for example, 4(5)-imidazoles, aminoglutethimide, MEGASE® (megestrol acetate), AROMASIN® (exemestane; Pfizer), formestane, fadrozole, RIVISOR® (vorozole), FEMARA® (letrozole; Novartis) and RIMIDEX® (anastrozole; AstraZeneca); (3) antiandrogens such as flutamide, nilutamide, bicalutamide, leuprolide and goserelin; as well as troxacitabine (1,3-dioxolane nucleoside analogue of cytosine); (4) protein kinase inhibitors, such as MEK inhibitors (WO 2007/044515); (5) lipid kinase inhibitors; (6) antisense oligonucleotides, in particular oligonucleotides that suppress the expression of genes in signaling pathways involved in aberrant cell proliferation, for example, PKC-alpha (protein kinase C) genes, Raf and H-Ras kinases, such as oblimersen (GENASENSE®, Genta Inc.); (7) ribozymes, such as inhibitors of vascular endothelial growth factor (VEGF) expression (eg, ANGIOZYME®) and inhibitors of HER2 (human epidermal growth factor receptor type 2) expression; (8) vaccines, such as gene therapy vaccines, for example, ALLOVECTIN®, LEUVECTIN® and VAXID®; recombinant interleukin-2 (rIL-2) PROLEUKIN®; topoisomerase 1 inhibitors such as LURTOTECAN®; rmRH ABARELIX®; (9) antiangiogenic agents such as bevacizumab (AVASTIN®, Genentech); and pharmaceutically acceptable salts, acids or derivatives of any of the above compounds.

Antibodies provided herein may include "chimeric" antibodies in which a portion of the heavy and/or light chain is identical or homologous to the corresponding sequence in antibodies derived from a particular species or belonging to a particular class or subclass of antibodies, while the remainder chain(s) identical or homologous to the corresponding sequence in antibodies derived from another species or belonging to another class or subclass of antibodies, as well as fragments of such antibodies, provided that they demonstrate the desired biological activity (see US patent No. 4816567 and Morrison et al ., Proc. Natl. Sci. USA, 81: 6851-6855 (1984).

As used herein, the term "composition" is intended to include a product containing specific ingredients (eg, the antibody provided herein) in as specific amounts as possible, as well as any product that results, directly or indirectly, from the combination of specific ingredients in possibly specific quantities.

"CDR" refers to one of three hypervariable regions (H1, H2 or H3) within the non-framework region of an immunoglobulin (Ig or antibody) VH β-sheet structure or to one of three hypervariable regions (L1, L2 or L3) within the non-framework regions of the VL antibody β-sheet structure. Accordingly, CDRs are sequences of variable regions interleaved within framework sequences. CDR regions are well known to those skilled in the art and have been identified, for example, by Kabat as regions of greatest hypervariability within the variable (V) domains of an antibody (Kabat et al., J. Biol. Chem, 252: 6609-6616 (1977); Kabat, Adv. Prot. Chem., 32: 1-75 (1978). In addition, the sequences of the CDR regions have been structurally defined by Chothia as those residues that are not part of the conserved β-sheet structure and are therefore capable of adopting different conformations (Chothia and Lesk, J. Mol. Biol., 196: 901-917 (1987) ). Both nomenclatures are generally accepted nomenclatures in the art. The sequences of the CDR regions were also determined according to the AbM, contact and IMGT databases. The sequences of the CDR regions are illustrated in FIG. 16A and 16B. The positions of the CDR regions within the canonical antibody variable domain have been determined by comparison of numerous structures (Al-Lazikani et al., J, Mol. Biol., 273: 927-948 (1997); Morea et al., Methods, 20: 267- 279 (2000)). Since the number of residues in the hypervariable region varies from antibody to antibody, additional residues compared to residues at the canonical positions are traditionally numbered a, b, c, and so on, following the number of residues in the canonical variable domain numbering scheme (Al-Lazikani et al., above (1997)). Such nomenclature is also well known to those skilled in the art.

The term "hypervariable region", "HVR" or "HV", as used herein, refers to regions of the variable domain of an antibody that have hypervariability in sequence and/or form loops with a specific structure. Typically, antibodies contain six hypervariable regions: three in VH (H1, H2, H3) and three in VL (L1, L2, L3). A number of methods for determining the boundaries of hypervariable regions are used and are included in this description. The Kabat definition of CDR is based on sequence variability and is the most commonly used (Kabat et. al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). Chothia, alternatively, refers to the location of structural loops (Chothia and Lesk, J. Mol. Bioi., 196: 901-917 (1987)). The end of the CDR-H1 no Chothia loop, when numbered using the Kabat numbering rule, varies between positions H32 and H34 depending on the length of the loop (this is because the Kabat numbering scheme allows for inserts at positions H35A and H35B; if neither there is no insert in position 35A or position 35B, then the loop ends in position 32; if the insert is present only in position 35A, then the loop ends in position 33; if there are inserts in both positions 35A and 35B, then the loop ends in position 34) . AbM hypervariable regions represent a compromise between Kabat CDRs and Chothia structural loops, and are used by Oxford Molecular's AbM software to model antibody structure. The location of hypervariable regions by the “contact” method is based on the analysis of the available crystal structures of the complexes. The residues of each of these hypervariable regions are indicated below.

Recently, the ImMunoGeneTics (IMGT) Information System® universal numbering system was developed and widely implemented (Lafranc et al., Dev. Comp. Immunol., 27(1): 55-77 (2003)). IMGT is an integrated information system specializing in immunoglobulins (Ig), T cell receptors (TR), and major histocompatibility complex (MHC) in humans and other vertebrates. Here, CDRs are specified both in terms of amino acid sequence and location in the light or heavy chain. Because the “location” of the CDRs in the immunoglobulin variable domain structure is conserved across species and is present in structures called loops, using numbering systems that align variable domain sequences according to structural features, it is easy to identify CDR and framework residues. This information can be used in the case of grafting and replacement of CDR residues from immunoglobulins of one type into an acceptor framework, usually from a human antibody. The correspondence between Kabat numbering and the unified IMGT numbering system is also well known to one skilled in the art (eg, Lefranc et al., supra) and is also illustrated in FIG. 16A and 16B. The typical system shown here combines the Kabat and Chothia systems.

Hypervariable regions may contain "extended hypervariable regions" as follows: 24-36 or 24-34 (L1), 46-56 or 50-56 (L2) and 89-97 or 89-96 (L3) in VL and 26- 35 or 26-35A (H1), 50-65 or 49-65 (H2) and 93-102, 94-102 or 95-102 (H3) in VH. The number of such variable domain residues is 25 according to Kabat et al., supra, for each of these definitions. As used herein, the terms "HVR" and "CDR" are used interchangeably.

The term "constant region" or "constant domain" refers to the carboxy-terminal portion of the light and heavy chain that is not directly involved in antibody-antigen binding but exhibits various effector functions, such as interaction with the Fc receptor. These terms refer to that part of the immunoglobulin molecule that has a more conserved amino acid sequence compared to the other part of the immunoglobulin, the variable domain, which contains the antigen-binding site. The constant domain contains the heavy chain constant CH1, CH2 and CH3 domains and the light chain constant CL domain.

The term "cycloalkyl" as used herein means a monocyclic or polycyclic radical that contains only carbon and hydrogen atoms, and includes radicals that are saturated, partially unsaturated or completely unsaturated. Cycloalkyl groups include groups having from 3 to 10 ring atoms.

In the context of a polypeptide, the term “derivative” as used herein refers to a polypeptide that contains the amino acid sequence of a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an antibody that binds to a C10orf54 polypeptide that has been altered by substitutions, deletions, or insertions of amino acid residues. The term “derivative” as used herein also refers to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an antibody that binds to a C10orf54 polypeptide that has been chemically modified, for example, by covalently attaching any type of molecule to the polypeptide. For example, but not by way of limitation, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody may be chemically modified, e.g., by glycosylation, acetylation, PEGylation, phosphorylation, amidation, derivatization using known protecting/blocking groups, resulting proteolytic cleavage, binding to a cellular ligand or other protein, etc. These derivatives are modified in such a way that they differ from the natural or original peptide or polypeptides either in the type or arrangement of the attached molecules. Derivations also include the deletion of one or more chemical groups that are naturally present in the peptide or polypeptide. A derivative of a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody may be chemically modified by chemical modification using methods known to those skilled in the art, including, but not limited to, specific chemical cleavage, acetylation, processing regimen, use of metabolic synthesis of tunicamycin, and etc. In addition, a derivative of a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an antibody to C10orf54 may contain one or more non-classical amino acids. The polypeptide derivative has a function similar or identical to the function of a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or an anti-C10orf54 antibody described herein.

The term “cytotoxic agent” or “cytotoxin” or “CTX” as used herein refers to a substance that inhibits or interferes with the functioning of cells and/or has a cytotoxic effect on cells (eg, causes cell destruction). The term is intended to include alkylating agents, anthracyclines, cytoskeletal damaging agents (taxanes), epothilones, histone deacetylase (HDAC) inhibitor, topoisomerase I inhibitor, topoisomerase II inhibitor, kinase inhibitor, monoclonal antibody, nucleotide analogue, peptide antibiotic, agent platinum-based, retinoids, vinca alkaloid or its derivative and a radioactive isotope. The term is also intended to include actinomycin, all-trans retinoic acid, azacitidine, azathioprine, bleomycin, bortezomib, carboplatin, capecitabine, cisplatin, chlorambucil, cyclophosphamide, cytarabine, daunorubicin, docetaxel, doxifluridine, doxorubicin, epirubicin, epothilone, etoposide , fluorouracil, gemcitabine, hydroxyurea, idarubicin, imatinib, irinotecan, mechlorethamine, mercaptopurine, methotrexate, mitoxantrone, oxaliplatin, paclitaxel, pemetrexed, teniposide, thioguanine, topotecan, valrubicin, vinblastine, vincristine, vindesine and vinorelbine. The term is also intended to include a tubulin stabilizer, a tubulin destabilizer, a DNA alkylating agent, a DNA small groove ligand, a DNA intercalator, a topoisomerase I inhibitor, a topoisomerase II inhibitor, a gyrase inhibitor, a protein synthesis inhibitor, a proteasome inhibitor, and an antimetabolite. The term is also intended to include actinomycin D, amonafide, auristatin, benzophenone, benzothiazole, calicheamicin, camptothecin, CC-1065 (NSC 298223), cemadotin, colchicine, combretastatin A4, dolastatin, doxorubicin, elinafide, emtansine (DM1), etoposide , KF-12347 (leinamycin), maytansinoid, methotrexate, mitoxantrone, nocodazole, proteasome inhibitor 1 (PSI 1), roridin A, T-2 toxin (trichothecene analogue), taxol, tubulisin, Velcade® and vincristine. Preferred cytotoxins include auristatin, calicheamicin, maytansinoid and tubulisin. Other preferred cytotoxins include monomethyl auristatin E (MMAE), monomethyl auristatin F (MMAF), calicheamicin γ, mertansine, T3 tubulisin and T4 tubulisin. Further preferred cytotoxins include calicheamicin, doxorubicin, camptothecin, duocarmycin, DM1, DM4, maytansinoid and tubulisin. Further preferred cytotoxins include MMAE, MMAF and pyrrolobenzodiazepine (PBD).

The term "MMAF" generally refers to monomethyl auristatin F, the chemical name for which is considered to be (S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4- ((S)-N,3-dimethyl-2-((S)-3-methyl-2-(methylamino)butanamido)butanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy -2-methylpropanamido)-3-phenylpropanoic acid. One of ordinary skill in the art will appreciate that MMAF is also described in the art as MeVal-Val-Dil-Dap-Phe, where "Dil" represents dolaisolein and "Dap" represents dolaproin.

The term "MMAE" usually refers to monomethyl auristatin E, the chemical name for which is considered to be (S)-N-((3R,4S,5S)-1-((S)-2-((1R,2R)-3-(( (1S,2R)-1-hydroxy-1-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1- oxoheptan-4-yl)-N,3-dimethyl-2-((3)-3-methyl-2-(methylamino)butanamido)butanamide.

The term "pyrrolobenzodiazepine" or "pyrrolobenzodiazepines" generally refers to a family of pyrrolo[2,1-c][1,4]benzodiazepine dimers (PBDs) that are synthetic, sequence-selective, interstrand cross-linkers in the DNA minor groove region , developed on the basis of anthramycins. Examples of pyrrolobenzodiazepines include, but are not limited to, abbeimycin, chikamycin, DC-81, mazethramycin, neothramycins A and B, porothramycin, protracarcin, sibanomycin (DC-102), sibiromycin and tomycin. Exemplary pyrrolobenzodiazepines include those described in US Pat. Nos. 7,049,311, 7,741,319, 8,697,688 (see, for example, (26) in Example 5) and 8,765,740; international patent applications with numbers WO 2011/130598 A1, WO 2012/112708 A1, WO 2013/055987 A1, WO 2013/165940 A1; and Jeffrey et al., Bioconjugate Speth., 2013, 24, 1256-1263 and Sutherland et al., Blood, 2013, 122(8), 1455-1463; provided that the contents of each are incorporated by reference in their entirety.

The structures for T3 and T4 are given below:

The structure for MMAF is given below:

(MMAF), the chemical name for which is "(S)-2-((2R,3R)-3-((S)-1-((3R,4S,5S)-4-((S)-N ,3-dimethyl-2-((S)-3-methyl-2-(methylamino)butanamido)butanamido)-3-methoxy-5-methylheptanoyl)pyrrolidin-2-yl)-3-methoxy-2-methylpropanamido)- 3-phenylpropanoic acid." One of ordinary skill in the art will appreciate that MMAF is also described in the art as MeVal-Val-Dil-Dap-Phe, where "Dil" represents dolaisolein and "Dap" represents dolaproin. The structure for MMAE is given below:

(MMAE), the chemical name for which is "(S)-N-((3R,4S,5S)-1-((S)-2-((1R,2R)-3-(((1S,2R )-1-hydroxy-1-phenylpropan-2-yl)amino)-1-methoxy-2-methyl-3-oxopropyl)pyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptane-4- yl)-N,3-dimethyl-2-((3)-3-methyl-2-(methylamino)butanamido)butanamide." One of ordinary skill in the art will appreciate that MMAE is also described in the art as MeVal-Val-Dil-Dap-norephedrine, where "Dil" represents dolaisolein and "Dap" represents dolaproine.

The structures for the three PBDs are given below:

wherein the chemical name is "(S)-11-hydroxy-7-methoxy-8-((5-(((S)-7-methoxy-2-methyl-5-oxo-5,11a-dihydro-1H -benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl)oxy)pentyl)oxy)-2-methyl-1H-benzo[e]pyrrolo[1,2-a][ 1,4]diazepin-5(11aH)-one"; And

wherein the chemical name is "(S)-2-(4-aminophenyl)-8-(3-(((S)-2-cyclopropyl-7-methoxy-5-oxo-5,11a-dihydro-1H- benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl)oxy)propoxy)-7-methoxy-1H-benzo[e]pyrrolo[1,2-a][1,4 ]diazepin-5(11aH)-one" (see, for example, compound (26) in example 5 of US patent No. 8697688); And

wherein the chemical name is "(S)-2-(4-aminophenyl)-7-methoxy-8-(3-(((S)-7-methoxy-2-(4-methoxyphenyl)-5-oxo- 5,11a-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]diazepin-8-yl)oxy)propoxy)-1H-benzo[e]pyrrolo[1,2-,4 ]diazepin-5(11aH)-one".

Other cytotoxic agents are known in the art, including various antitumor or anticancer agents.

The term "detection probe" as used herein refers to a compound that provides a detectable signal. The term includes, without limitation, any fluorophore, chromophore, radiolabel, enzyme, antibody or antibody fragment, and the like, which provides a detectable signal due to its activity.

The term "diagnostic agent" refers to a substance administered to a subject that assists in the diagnosis of a disease. Such substances can be used to identify, pinpoint and/or localize the disease-causing process. In certain embodiments, the diagnostic agent includes a substance conjugated to an antibody provided herein that, when administered to a subject or in contact with a sample obtained from the subject, assists in the diagnosis of cancer, tumorigenesis, or any other C10orf54-mediated disease.

The term "detectable agent" refers to a substance that can be used to determine the presence or presence of a desired molecule, such as an antibody provided herein, in a sample or body of a subject. The detectable agent may be a substance that can be visualized, or a substance that can be determined and/or otherwise measured (eg, by quantitation).

An "effective amount" is an amount sufficient to produce beneficial or desired results. An effective amount may be administered in one or more than one administration, application or dosing procedure. Such delivery depends on a number of variable parameters, including the period of time over which a particular dosage unit should be used, the bioavailability of the agent, the route of administration, etc. In some embodiments, an effective amount also refers to the amount of an antibody of this invention necessary to achieve the intended result (eg, inhibiting C10orf54-associated cell biological activity, such as modulating T cell activation and/or proliferation). In some embodiments, the term refers to a therapeutic dosage (eg, of an antibody or pharmaceutical composition provided herein) that is sufficient to reduce and/or ameliorate the severity and/or duration of a particular disease and/or associated symptom. The term also covers an amount necessary to reduce or attenuate the development or progression of a specified disease, reduce or reduce the likelihood of relapse, development or onset of a specified disease, and/or improve or enhance the prophylactic or therapeutic effect(s) of other therapy ( for example, a therapy other than the anti-C10orf54 antibody provided herein). In some embodiments, the effective amount of the antibody is from about 0.1 mg/kg (mg of antibody per kg of subject's body weight) to about 100 mg/kg. In certain embodiments, the effective amount of an antibody provided herein is about 0.1 mg/kg, about 0.5 mg/kg, about 1 mg/kg, 3 mg/kg, 5 mg/kg, about 10 mg/kg , approximately 15 mg/kg, approximately 20 mg/kg, approximately 25 mg/kg, approximately 30 mg/kg, approximately 35 mg/kg, approximately 40 mg/kg, approximately 45 mg/kg, approximately 50 mg/kg, approximately 60 mg/kg, about 70 mg/kg, about 80 mg/kg, about 90 mg/kg, or about 100 mg/kg (or in this range).

The term "electrophilic leaving group" as used herein refers to a leaving group that is an electron pair acceptor in the formation of a covalent bond. In general, electrophiles are susceptible to attack by conjugated nucleophiles, including thiols that result from reduction of the antibody disulfide bond.

The term "electrophilic leaving group that selectively reacts with thiols" as used herein refers to an electrophilic leaving group that selectively reacts with thiols over other nucleophiles. In certain embodiments, an electrophilic leaving group that selectively interacts with thiols selectively interacts with thiols that result from reduction of the antibody disulfide bond.

The term "encode" or its grammatical equivalents when used in relation to a nucleic acid molecule, refers to a nucleic acid molecule in its native state or when manipulated by methods well known to those skilled in the art, which can be transcribed to produce mRNA and which is then translated into a polypeptide and/or fragment thereof. The antisense strand is complementary to such a nucleic acid molecule and a coding sequence can be derived from it.

The term "epitope" as used herein refers to a localized region on the surface of an antigen, such as a C10orf54 polypeptide or a fragment of a C10orf54 polypeptide, that is capable of binding to one or more antigen-binding sites of an antibody and that in an animal, such as a mammal (e.g., a human) has antigenic or immunogenic activity, that is, it is capable of causing an immune response. An immunogenic epitope is the portion of a polypeptide that elicits an antibody response in an animal. An epitope having antigenic activity is the portion of a polypeptide to which an antibody binds, as determined by any method well known in the art, for example, using an immunoassay. Antigenic epitopes do not necessarily have to be immunogenic. Epitopes typically consist of chemically active surface moieties of molecules, such as amino acids or sugar side chains, and have specific three-dimensional structural characteristics as well as specific charge characteristics. The region of the polypeptide constituting an epitope may be contiguous amino acids of the polypeptide, or the epitope may be composed of two or more non-contiguous regions of the polypeptide. The epitope may or may not be a spatial component of the antigen surface. In certain embodiments, the C10orf54 epitope is a spatial component of the surface of the C10orf54 polypeptide. In other embodiments, the C10orf54 epitope is a linear component of a C10orf54 polypeptide. Typically, an antigen has several or many different epitopes and interacts with many different antibodies.

The term "excipient" as used herein refers to an inert substance that is typically used as a diluent, excipient, preservative, binder, or stabilizing agent, and includes, but is not limited to, proteins (e.g., serum albumin, etc. .), amino acids (e.g. aspartic acid, glutamic acid, lysine, arginine, glycine, histidine, etc.), fatty acids and phospholipids (e.g. alkyl sulfonates, caprylate, etc.), surfactants (e.g. , SDS (sodium dodecyl sulfate), polysorbate, non-ionic surfactant, etc.), saccharides (eg sucrose, maltose, trehalose, etc.) and polyols (eg mannitol, sorbitol, etc.) . See also Remington's Pharmaceutical Sciences (1990) Mack Publishing Co., Easton, PA, which is hereby incorporated by reference in its entirety.

When referring to a peptide or polypeptide, the term "fragment" as used herein refers to a peptide or polypeptide that contains an amino acid sequence less than full length. Such a fragment may arise, for example, as a result of truncation at the amino-terminal portion, truncation at the carboxy-terminal portion, and/or deletion of residue(s) within the amino acid sequence. For example, fragments may be generated by alternative RNA splicing or by protease activity in vivo. In certain embodiments, C10orf54 fragments include polypeptides comprising an amino acid sequence consisting of at least 5 contiguous amino acid residues, at least 10 contiguous amino acid residues, at least 15 contiguous amino acid residues, at least 20 contiguous amino acid residues, at least 25 contiguous amino acid residues, at least 40 contiguous amino acid residues, at least 50 contiguous amino acid residues, at least 60 contiguous amino acid residues, at least 70 contiguous amino acid residues, at least 80 contiguous amino acid residues, at least 90 contiguous amino acid residues, at least 100 contiguous amino acid residues, at least 125 contiguous amino acid residues, at least 150 contiguous amino acid residues, at least 175 contiguous amino acid residues, at least of at least 200 contiguous amino acid residues or at least 250 contiguous amino acid residues of the amino acid sequence of a C10orf54 polypeptide or an antibody that binds to a C10orf54 polypeptide. In a specific embodiment, a C10orf54 polypeptide fragment or antibody that binds to a C10orf54 antigen retains at least 1, at least 2, or at least 3 functions of the polypeptide or antibody.

The term "framework" or "FR" residues refers to the variable domain residues flanking the CDRs. FR residues are present, for example, in chimeric, humanized, human, single domain antibodies, diabodies, linear antibodies and bispecific antibodies. FR residues are those variable domain residues that differ from the hypervariable region residues as defined herein.

A "functional fragment" of an antibody will exhibit at least one biological function, if not some or all of the biological functions inherent in the intact antibody, which function is at least specific binding to a target antigen.

The term "fusion protein" as used herein refers to a polypeptide that contains the amino acid sequence of an antibody and the amino acid sequence of a heterologous polypeptide or protein (e.g., a polypeptide or protein not normally part of an antibody (e.g., not an antibody to the C10orf54 antigen) ). The term “fusion,” when used in connection with C10orf54 or an anti-C10orf54 antibody, refers to the joining of a peptide or polypeptide, or a fragment, variant and/or derivative thereof, to a heterologous peptide or polypeptide. In certain embodiments, the fusion protein retains the biological activity of C10orf54 or an anti-C10orf54 antibody. In certain embodiments, the fusion protein comprises a VH domain, a VL domain, a VH CDR (one, two, or three VH CDRs), and/or a VL CDR (one, two, or three VL CDRs) of an anti-C10orf54 antibody, wherein the fusion protein binds to an epitope C10orf54.

The term “heavy chain,” when used in connection with an antibody, refers to a polypeptide chain of about 50-70 kDa in size, the amino-terminal portion of which includes a variable region of about 120-130 or more amino acids, and the carboxy-terminal portion of which includes constant region. The constant region can be one of five different types, called alpha (α), delta (δ), epsilon (ε), gamma (γ), and mu (μ), based on the amino acid sequence of the heavy chain constant region. These different heavy chains differ in size: α, δ and γ contain approximately 450 amino acids, while μ and ε contain approximately 550 amino acids. When combined with the light chain, these different types of heavy chains give rise to five well-known classes of antibodies: IgA, IgD, IgE, IgG and IgM, respectively, including four subclasses of IgG, namely IgG1, IgG2, IgG3 and IgG4. The heavy chain may be a human immunoglobulin heavy chain.

The term "host" as used herein refers to an animal, such as a mammal (eg, a human).

The term “host cell” as used herein refers to the specific affected cell transfected with the nucleic acid molecule and the progeny or possible progeny of such cell. The progeny of such a cell may not be identical to the parent cell transfected with the nucleic acid molecule, due to mutations or environmental influences that may occur in subsequent generations, or due to the incorporation of the nucleic acid molecule into the genome of the host cell.

"Humanized" forms of non-human (e.g., murine) antibodies are chimeric antibodies comprising human immunoglobulins (recipient antibody) in which the native CDR residues are replaced with residues from the corresponding CDR of a non-human species (donor antibody), such as mouse, rat, rabbit or non-human primate having the desired specificity, affinity and functional activity. In some cases, one or more residues of the FR region of a human immunoglobulin are replaced with corresponding immunoglobulin residues from a non-human species. In addition, humanized antibodies may contain residues that are not found in the recipient antibody or the donor antibody. These modifications are made to further improve the effectiveness of the antibodies. A humanized antibody heavy or light chain may comprise substantially all of at least one or more variable domains, in which all or substantially all of the CDRs correspond to those of a non-human immunoglobulin, and all or substantially all of the FRs are FRs from the sequence human immunoglobulin. In certain embodiments, the humanized antibody will comprise at least a portion of an immunoglobulin constant region (Fc), typically a human immunoglobulin constant region. For further details, see Jones et al., Nature, 321: 522-525 (1986); Riechmann et al., Nature, 332: 323-329 (1988); and Presta, Curr. Op. Struct. Biol., 2: 593-596 (1992); Carter et al., Proc. Natl. Acd. Sci. USA, 89: 4285-4289 (1992); and US Patent Nos. 6800738 (Published October 5, 2004), 6719971 (Published September 27, 2005), 6639055 (Published October 28, 2003), 6407213 (Published June 18, 2002) and 6054297 (Published April 25 2000).

An antibody that "inhibits the growth of cells expressing C10orf54 and/or kills these cells" or a "growth inhibitory" or "cytotoxic" antibody is an antibody that results in a significant increase in the inhibition and/or killing of cells expressing or overexpressing the corresponding polypeptide is C10orf54. In some embodiments, such antibodies can inhibit the growth of cells expressing C10orf54 and/or kill these cells. Such cells include regulatory T cells (eg, CD4 ⁺ Foxp3 ⁺ regulatory T cells), myeloid suppressor cells (eg, CD11b ⁺ or CD11b ^high myeloid suppressor cells), and/or suppressive dendritic cells (eg, CD11b ⁺ or CD11b ^high dendritic cells). In a specific embodiment, the antibodies inhibit the growth of a cancer cell, precancerous cell or tumor cell, and/or destroy such cells. Some growth inhibitory antibodies to C10orf54 inhibit the growth of C10orf54-expressing cells and/or kill such cells by more than 20%, such as from about 20% to about 50% or more than 50% (for example, from about 50% to about 100%) compared to the corresponding control, usually using cells not treated with the test antibody as a control. In one embodiment, growth inhibition and/or killing can be measured at an antibody concentration in the cell culture of about 0.1 to 30 g/mL, or about 0.5 nM to 200 nM, with growth inhibition measured after 1 to 10 days after exposure of the antibody to tumor cells. Growth inhibition and/or cell killing in vivo can be determined by various methods, such as those described below. In the context of inhibiting a cancer cell or tumor cell, the antibody exhibits growth inhibition or killing in vivo if administration of the anti-C10orf54 antibody in an amount of from about 1 g/kg to about 100 mg/kg body weight results in a decrease in tumor size or decrease in tumor cell proliferation within from about 5 days to 3 months from the start of the first administration of the antibody, for example, ranging from about 5 days to 30 days.

As used herein, the term “in combination” in the context of administering other therapeutic agents refers to the use of more than one therapy. The use of the term “in combination” does not limit the order in which the therapeutic agents are administered to a subject having an infection. The first therapeutic agent may be administered prior to administration (e.g., 1 minute, 45 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, or 12 weeks), simultaneously with or after administration (e.g., after 1 minute, 45 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks or 12 weeks) second therapeutic funds to a subject who has had, has, or is susceptible to a C10orf54-mediated disease. Any additional therapeutic agent can be administered in any order with other additional therapeutic agents. In certain embodiments, antibodies may be administered in combination with one or more therapeutic agents (e.g., non-antibody therapeutic agents currently administered to prevent, treat, inhibit, and/or mitigate C10orf54-mediated disease. Non-limiting Examples therapeutic agents that can be administered in combination with the antibody include analgesics, anesthetics, antibiotics or immunomodulatory agents or any other agent listed in the US Pharmacopeia and/or Physician's Desk Reference.

An antibody that "induces cell death" is an antibody that causes a viable cell to become nonviable. This cell is a cell type that specifically expresses or overexpresses the C10orf54 polypeptide. The cell may be a cancer cell or a normal cell of a particular cell type, such as a regulatory T cell. Cell death in vitro can be determined in the absence of complement and immune effector cells to distinguish it from cell death caused by antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). Thus, cell death assays can be performed using heat-inactivated blood serum (eg, in the absence of complement) and in the absence of immune effector cells. To determine whether a given antibody is capable of causing cell death, loss of membrane integrity is assessed by the uptake of propidium iodide (PI), trypan blue (see Moore et al., Cytotechnology, 17: 1-11 (1995)). In some embodiments, the cell death-inducing antibodies are antibodies that induce PI uptake in a PI uptake assay in C10orf54-expressing cells.

An "isolated" antibody is substantially free of cellular material or other contaminating proteins from the cellular or tissue source and/or other contaminating components from which the antibody is derived, or substantially free of chemical precursors or other chemical reagents used during chemical synthesis. The expression "substantially free of cellular material" includes antibody preparations in which the antibody is separated from the cellular components of the cells from which it is isolated or recombinantly produced. Thus, an antibody that is substantially free of cellular material includes antibody preparations containing less than about 30%, 20%, 10%, or 5% (by dry weight) of a heterologous protein (also referred to herein as a “contaminant protein "). In certain embodiments, when an antibody is produced recombinantly, it is substantially free of culture medium, for example, the culture medium constitutes less than about 20%, 10%, or 5% of the volume of the protein preparation. In certain embodiments, when an antibody is produced by chemical synthesis, it is substantially free of chemical precursors or other chemical reagents, for example, it is separated from chemical precursors or other chemical reagents involved in protein synthesis. Accordingly, such antibody preparations contain less than about 30%, 20%, 10%, 5% (by dry weight) chemical precursors or compounds other than the antibody of interest. Contaminants may also include, but are not limited to, materials that would interfere with therapeutic applications of the antibody, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes. In certain embodiments, the antibody will be purified (1) to greater than 95% by weight of the antibody, as determined by the Lowry method (Lowry et al., J. Bio. Chem., 193: 265-275, 1951), for example, to 99% by weight mass, (2) to an extent sufficient to obtain at least 15 residues at the N-termini or within the amino acid sequence using a spin-beaker sequencer, or (3) to a homogeneous state as determined by SDS-PAGE (polyacrylamide gel electrophoresis in the presence of SDS) under reducing or non-reducing conditions using Coomassie blue or preferably silver staining. An isolated antibody includes an antibody that resides in situ within recombinant cells after at least one component of the antibody's natural environment is no longer present. Typically, however, at least one purification step will be used in obtaining the isolated antibody. In a specific embodiment, the antibodies provided herein are isolated or purified.

An "isolated" nucleic acid molecule is a molecule separated from other nucleic acid molecules that are present in a natural source of nucleic acid molecules. In addition, an “isolated” nucleic acid molecule, such as a cDNA molecule, may be substantially free of other cellular material or culture medium when produced by recombinant methods, or may be substantially free of chemical precursors or other chemical reagents if chemically synthesized. In a specific embodiment, the nucleic acid molecule(s) encoding the antibody of the present invention are isolated or purified.

The term "leaving group" as used herein refers to any group that is removed during a chemical reaction involving that group as described herein and includes, but is not limited to, halogen, sulfonates (brosylate, mesylate , tosylate, triflate, etc.), p-nitrobenzoate and phosphonate groups.

The term "light chain", when used with reference to an antibody, refers to a polypeptide chain of about 25 kDa in size, where the amino-terminal portion includes a variable region consisting of from about 100 to about 110 or more amino acids, and the carboxy-terminal portion includes a constant region region. The approximate length of the light chain is 211-217 amino acids. Based on the amino acid sequence of the constant domains, there are two different types of chains called kappa (κ) or lambda (λ). Light chain amino acid sequences are well known in the art. The light chain may be a human immunoglobulin light chain.

A "linker" (designated L or L ¹ , L ² and L ³ ) is a molecule having two reactive ends, one for conjugation with an antibody or other linker, and the other for conjugation with a cytotoxin. The reactive end of the antibody conjugation linker is typically a site suitable for conjugation to the antibody via the cysteine thiol group or lysine amino group of the antibody and is thus typically a thiol-reactive group such as a double bond (as in a maleimide), or a leaving group such as a chlorine, bromine or iodine atom, or an R-sulfanyl group, or a sulfonyl group, or an amine-reactive group such as a carboxyl group, or as defined herein; in addition, the reactive end of the antibody conjugation linker is typically a site suitable for conjugation to a cytotoxin by forming an amide bond with a basic amino group or carboxyl group of the cytotoxin and is thus typically a carboxyl group or basic amino group. In one embodiment, when the term "linker" is used to describe a linker in conjugated form, one or both of the reactive ends will be absent (e.g., no leaving group in the case of a thiol-reactive group) or will be incomplete (e.g., only carbonyl carboxylic acid) due to the formation of bonds between the linker and/or cytotoxin. The linkers described herein may be cleavable under normal physiological and/or intracellular conditions or may remain stable (eg, non-cleavable or non-cleavable) under these same conditions. Examples of cleavable linkers are linkers that contain dipeptide moieties, where the peptide bond connecting the two peptides can be selectively cleaved by lysosomal proteases (eg, cathepsin-B). The dipeptide moiety commonly used in cleavable linkers is valine-citrulline (Val-Cit).

As used herein, the terms “inhibit development,” “implement developmental inhibition,” and “inhibit development” refer to the beneficial effects obtained by a subject from a therapy (eg, as a result of the use of a prophylactic or therapeutic agent) that do not result in a cure of the disease. In certain embodiments, a subject is administered one or more therapeutic agents (e.g., prophylactic or therapeutic agents, such as an antibody provided herein) to "inhibit the progression" of a C10orf54-mediated disease, one or more of its symptoms, so that prevent progression or exacerbation of the disease.

The term "monoclonal antibody" refers to an antibody derived from a population of homogeneous or substantially homogeneous antibodies, and each monoclonal antibody will generally recognize one epitope of an antigen. In specific embodiments, the term "monoconeal antibody" as used herein means an antibody produced by a single hybridoma or other cell, wherein the antibody binds only to the C10orf54 epitope, as determined, for example, using an ELISA or other antigen binding or competitive binding assay , known in the art. The term "monoponal" is not limited to any particular method of producing an antibody. For example, the monoclonal antibodies provided herein can be produced by the hybridoma method as described in Kohler et al., Nature, 256:495 (1975), or can be produced using isolation methods from phage libraries. Other methods for generating clonal cell lines and the monoclonal antibodies they express are well known in the art (see, for example, Chapter 11 in Short Protocols in Molecular Biology, (2002) 5th Ed., Ausubel et al., eds., John Wiley and Sons, New York). Other exemplary methods for producing other monoclonal antibodies are provided herein in the Examples section.

The term "natural", when used in reference to biological materials such as nucleic acid molecules, polypeptides, host cells and the like, refers to those that occur naturally and are not derived from human activities

The term "pharmaceutically acceptable" as used herein means "approved for use by a federal or state regulatory agency" or listed in the United States Pharmacopoeia, European Pharmacopoeia, or other generally accepted pharmacopoeia for use in animals and, more specifically, in humans.

The term "polyclonal antibodies" as used herein refers to a population of antibodies formed as a result of an immune response to a protein that has many epitopes, and therefore includes many different antibodies directed to the same and different epitopes of a given protein. Methods for producing polyclonal antibodies are known in the art (see, for example, Chapter 11 in Short Protocols in Molecular Biology, (2002) 5th Ed., Ausubel et al., eds., John Wiley and Sons, New York).

As used herein, the term "polynucleotide", "nucleotide", "nucleic acid", "nucleic acid molecule" and other similar terms are used interchangeably and include DNA, RNA, mRNA and the like.

The term "precancerous cell" refers to a cell that has an abnormal appearance, such as a different size or shape from surrounding tissue cells or normal cells of its type, but is not invasive. The appearance of precancerous cells may indicate an increased risk of cancer. Precancerous cells expressing C10orf54 can be identified using the methods set forth herein, which may include analysis of a sample of cells isolated from the patient.

As used herein, the terms "prevent", "prevent" and "prevent" refer to the complete or partial inhibition of the development, recurrence, onset or spread of a C10orf54-mediated disease and/or associated symptom as a result of administration of a therapeutic agent or combination of therapeutic agents, proposed in this application (for example, combinations of prophylactic or therapeutic agents, such as the antibody proposed in this application).

As used herein, the term “prophylactic agent” refers to any agent that can completely or partially inhibit the development, relapse, onset or spread of a C10orf54-mediated disease and/or associated symptom in a subject. In certain embodiments, the term “prophylactic agent” refers to the anti-C10orf54 antibody provided herein. In certain other embodiments, the term “prophylactic agent” refers to an agent other than the anti-C10orf54 antibody provided herein. In certain embodiments, a prophylactic agent is an agent that is known to be useful or has been used or is currently used to prevent a C10orf54-mediated disease and/or associated symptom or prevent the onset, development, progression and/or help reduce the severity of a C10orf54-mediated disease disease and/or associated symptom. In specific embodiments, the prophylactic agent is a humanized anti-C10orf54 antibody, such as a humanized monopole anti-C10orf54 antibody.

In certain embodiments, a “prophylactically effective serum titer” is a serum titer in a subject, preferably a human, that completely or partially inhibits the development, relapse, onset or spread of a C10orf54-mediated disease and/or associated symptom in the subject.

The term "recombinant antibody" refers to an antibody that is produced, expressed, created or isolated using recombinant methods. Recombinant antibodies can be antibodies expressed using a recombinant expression vector with which a host cell has been transfected, antibodies isolated from combinatorial libraries of recombinant antibodies, antibodies isolated from an animal (for example, mouse or cow) that are transgenic and/or transchromosomal for immunoglobulin genes human (see, for example, Taylor L. D. et al. (1992) Nucl. Acids Res., 20: 6287-6295), or antibodies produced, expressed, created or isolated using any other method that involves splicing immunoglobulin gene sequences with other DNA sequences. Such recombinant antibodies may have variable and constant regions derived from human germline immunoglobulin sequences (see Kabat E. A. et al. (1991) Sequences of Proteins of Immunological Interest, fifth edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242). However, in certain embodiments, such recombinant antibodies are subject to in vitro mutagenesis (or, in the case of an animal transgenic for human Ig sequences, somatic mutagenesis in vivo) and thus the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences which, being derived from and related to VH and VL sequences from human germline antibodies, cannot naturally exist in the human germline antibody repertoire in vivo.

The term "serum titer" as used herein refers to the average serum titer in a group of at least 10, such as at least 20 or at least 40 subjects, up to about 100, 1000 or more.

As used herein, the term “side effects” encompasses undesirable and unfavorable effects of a therapeutic agent (eg, a prophylactic or therapeutic agent). Undesired effects are not necessarily unfavorable. An adverse effect of a therapeutic agent (eg, a prophylactic or therapeutic agent) may be harmful or unpleasant, or may be associated with risk. Examples of side effects include, diarrhea, cough, gastroenteritis, wheezing, nausea, vomiting, anorexia, abdominal cramps, fever, pain, weight loss, hypohydration, alopecia, shortness of breath, insomnia, dizziness, mucositis, nerve and muscle effects , fatigue, dry mouth and decreased appetite, rashes or swelling at the injection site, flu-like symptoms such as fever, chills and fatigue, digestive problems and allergic reactions. Additional undesirable effects experienced by patients are numerous and known in the art. Many of them are described in the Doctor's Desk Reference (67th ed., 2013).

As used herein, the terms “subject” and “patient” are used interchangeably. As used herein in certain embodiments, the subject is a mammal, such as a non-primate mammal (eg, cattle, pigs, horses, cats, dogs, rats, etc.) or a primate (eg, monkey and human) ). In specific embodiments, the subject is a person. In one embodiment, the subject is a mammal (eg, human) having a C10orf54-mediated disease. In another embodiment, the subject is a mammal (eg, a human) at risk of developing a C10orf54-mediated disease.

As used herein, "substantially all" means at least about 60%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or about 100%.

As used herein, the term “therapeutic agent” refers to any agent that can be used to treat, prevent or alleviate a disease, disorder or condition, including treating, preventing or alleviating one or more symptoms of a C10orf54-mediated disease, disorder or condition and/or associated symptom. In certain embodiments, the term “therapeutic agent” refers to the antibody provided herein. In certain other embodiments, the term “therapeutic agent” refers to an agent other than the antibody provided herein. In certain embodiments, a therapeutic agent is an agent that is known to be useful or has been or is currently used for treating, preventing, or alleviating one or more symptoms of a C10orf54 mediated disease, disorder, condition, or related symptom.

The effect of a combination of therapeutic agents (eg, the use of therapeutic agents) may be greater than the additive effects of any two or more monotherapies. For example, the synergistic effect of a combination of therapeutic agents allows the use of lower dosages of one or more agents and/or the use of less frequent administration of agents to a subject with a C10orf54-mediated disease. The ability to use lower dosages when treating therapeutics and/or administer therapeutics less frequently reduces the toxicity associated with administering therapeutics to a subject without reducing the effectiveness of the therapeutics in preventing, treating, or alleviating one or more than one symptom of a C10orf54-mediated disease. In addition, the synergistic effect may result in improved effectiveness of therapeutic agents for preventing, treating, or alleviating one or more symptoms of a C10orf54-mediated disease. Finally, the synergistic effect of a combination of therapeutic agents (eg, therapeutic agents) may prevent or reduce adverse or undesirable side effects associated with the use of any monotherapy.

The term "therapeutically effective amount" as used herein refers to an amount of a therapeutic agent (e.g., an antibody provided herein or any other therapeutic agent provided herein) that is sufficient to reduce and/or alleviate the severity and/or or the duration of a particular disease and/or associated symptom. A therapeutically effective amount of a therapeutic agent may be the amount necessary to reduce or attenuate the development or progression of a particular disease, reduce or reduce the likelihood of relapse, development or onset of a particular disease, and/or improve or enhance the prophylactic or therapeutic effect(s). ) other therapy (for example, therapy other than the use of the antibody proposed in this application).

In certain embodiments, a “therapeutically effective serum titer” is a serum titer in a subject, preferably a human, that reduces the severity, duration and/or ameliorates symptoms associated with a C10orf54-mediated disease in the subject.

As used herein, the term “therapy” refers to any protocol, method and/or agent that can be used to prevent, inhibit, treat and/or alleviate a C10orf54-mediated disease. In certain embodiments, the terms "therapies" and "therapy" refer to biological therapies, supportive therapies, and/or other therapies useful for preventing, inhibiting, treating, and/or mitigating C10orf54-mediated disease known to one skilled in the art, such as representative of the medical staff.

The term "thiol" as used herein refers to the -SH radical.

As used herein, the terms “treat,” “treating,” and “treating” refer to reducing and/or attenuating the progression, severity, and/or duration of a C10orf54-mediated disease as a result of the administration of one or more than one therapeutic agent (including, but not limited to the administration of one or more therapeutic agents, such as the antibody provided herein). In specific embodiments, such terms refer to the attenuation or inhibition of cancer or tumorigenesis. In other specific embodiments, such term refers to reducing and/or attenuating the progression, severity and/or duration of graft-versus-host disease. In other specific embodiments, such terms refer to reducing and/or attenuating the progression, severity and/or duration of a disease that is susceptible to immune modulation, such as modulation resulting from increased T cell activation, increased T cell proliferation, or increased cytokine production .

The term "tubulisin" includes both natural products described as tubulisins, for example, Sasse et al. and others mentioned in the related prior art, and tubulisin analogs described in published US patent application No. US 2011/0021568 A1. The tubulisins disclosed herein are those noted herein and may include tubulisins of formulas T3 and T4 and other tubulisins where the terminal N-methylpiperidine is replaced by an unsubstituted piperidine, allowing the formation of an amide bond with the linker.

The term "variable domain" or "variable region" refers to a portion of an antibody's light or heavy chain that is generally located at the amino-terminal portion of the light or heavy chain, has a length of about 120 to 130 amino acids in the heavy chain, and is about 100 to The 110 amino acids in the light chain are used to bind each specific antibody to its specific antigen and determine the specificity of each specific antibody for its specific antigen. Variable domains vary greatly in sequence among different antibodies. Variation in the sequence is concentrated in the CDRs, while the less variable portions in the variable domain are called framework regions (FRs). The light and heavy chain CDRs are primarily responsible for the interaction of the antibody with the antigen. In specific embodiments, the variable region is a human immunoglobulin variable region.

The term “Kabat variable domain residue numbering” or “Kabat amino acid position numbering” and variations thereof refer to the numbering system used for heavy chain variable domains or light chain variable domains in the synthesis of antibody data in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991). When using this numbering system, the actual linear amino acid sequence may contain fewer amino acids or contain additional amino acids in accordance with the shortening of the FR or CDR of the variable domain or insertion into the FR or CDR of the variable domain. For example, the heavy chain variable domain may include a single amino acid insert (Kabat residue 52a) after residue 52 in H2 and inserted residues (eg, Kabat residues 82a, 82b and 82c, etc.) after residue 82 in the heavy chain FR. Kabat residue numbering can be determined for a given antibody by aligning regions of homology of the antibody sequence with the Kabat numbered “standard” sequence. The Kabat numbering system is typically used when referring to a residue in a variable domain (approximately residues 1-107 of the light chain and residues 1-113 of the heavy chain) (eg, Kabat et al., Sequences of Immunological Interest. 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (1991). The "EU numbering system" or "EU index" is typically used when referring to a residue in the constant region of an immunoglobulin heavy chain (eg, the EU index given in Kabat et al., supra). The term "Kabat EU index" refers to the residue numbering of the human IgG1 EU antibody. Unless otherwise indicated herein, references to residue numbers in the antibody variable domain indicate residue numbering according to the Kabat numbering system. Other numbering systems have been described, including, for example, the AbM database, Chothia, the contact method, and IMGT. Various numbering systems are illustrated in FIG. 16A and 16B.

The term “variant,” when used in relation to C10orf54 or an anti-C10orf54 antibody, refers to a peptide or polypeptide containing one or more (e.g., about 1 to about 25, about 1 to about 20, about 1 to about 15, from about 1 to about 10 or from about 1 to about 5) substitutions, deletions and/or insertions in the amino acid sequence compared to the native or unmodified sequence. For example, a C10orf54 variant may result from one or more (e.g., about 1 to about 25, about 1 to about 20, about 1 to about 15, about 1 to about 10, or about 1 to about 5) changes in the amino acid sequence of native C10orf54. Also by way of example, an anti-C10orf54 antibody variant may result from one or more (e.g., about 1 to about 25, about 1 to about 20, about 1 to about 15, about 1 to about 10, or about 1 up to about 5) changes in the amino acid sequence of a native or previously unmodified anti-C10orf54 antibody. Variants may be naturally occurring, such as allelic or splice variants, or may be artificially engineered. Polypeptide variants can be derived from the corresponding nucleic acid molecules encoding the variants. In specific embodiments, the C10orf54 variant or the anti-C10orf54 antibody variant at least retains the functional activity of the C10orf54 or the anti-C10orf54 antibody, respectively. In specific embodiments, the anti-C10orf54 antibody variant binds to C10orf54 and/or exhibits C10orf54 antagonistic activity. In specific embodiments, the anti-C10orf54 antibody variant binds to C10orf54 and/or exhibits agonistic activity against C10orf54. In certain embodiments, the variant is encoded by a variant of a single nucleotide polymorphism (SNP) nucleic acid molecule that encodes C10orf54 or the VH or VL regions or subregions of an anti-C10orf54 antibody.

The term "vector" refers to a substance that is used to introduce a nucleic acid molecule into a host cell. Suitable vectors include, for example, expression vectors, plasmids, phage vectors, viral vectors, episomes and artificial chromosomes, which may include selection sequences or selectable markers suitable for stable integration into the host cell chromosome. In addition, the vectors may include one or more selectable marker genes and corresponding expression control sequences. Selectable marker genes that can be introduced provide, for example, resistance to antibiotics or toxins, auxotrophic complement deficiency, or the supply of essential nutrients not available in culture media. Expression control sequences may include constitutive and inducible promoters, transcription enhancers, transcription terminators, and the like, which are well known in the art. When two or more nucleic acid molecules are expressed together (eg, for both heavy and light chains of an antibody), both nucleic acid molecules can be inserted, for example, into the same expression vector or into different expression vectors. In the case of a single expression vector, the encoded nucleic acids may be operably linked to one common expression control sequence or may be linked to different expression control sequences, such as one inducible promoter and one constitutive promoter. Introduction of nucleic acid molecules into a host cell can be confirmed using methods well known in the art. Such methods include, for example, nucleic acid analysis such as Northern blotting, or mRNA amplification using polymerase chain reaction (PCR), or immunoblotting to analyze the expression of gene products, or other suitable analytical methods for testing the expression of the introduced nucleic acid sequence or its corresponding gene product. Those skilled in the art will appreciate that the nucleic acid molecule is expressed in sufficient quantity to produce the desired product (e.g., the anti-C10orf54 antibody provided herein), and it will also be understood that expression levels can be optimized to obtain sufficient expression using methods well known in the art.

BRIEF DESCRIPTION OF GRAPHIC MATERIALS

In FIG. 1A and 1B show the expression level of C10orf54 protein, which was identified and quantified using sTAg (surface target antigen profiling) assay in AML and BMMC (bone marrow mononuclear cell) samples and matched controls.

In FIG. Figure 2 shows the results of FACS analysis of 23 samples of primary AML-BM-MNC (bone marrow mononuclear cells) and 3 samples of normal BM-MNC using the anti-C10orf54 antibody 76E1.

In FIG. 3A and 3B show humanized sequences for the VH region of the mouse monoclonal antibody 76E1. SEQ ID NOs shown: 1, 7, 8, 12-15 and 82.

In FIG. 4A and 4B show humanized sequences for the VH region of mouse monoclonal antibody 141A. SEQ ID NOs shown: 2, 7, 8, 16-19 and 82.

In FIG. 5A and 5B show humanized sequences for the VH region of the mouse monoclonal antibody 175A. SEQ ID NOs shown: 3, 7, 8, 20-23 and 82.

In FIG. 6A and 6B show humanized sequences for the VL region of the mouse monoclonal antibody 76E1. SEQ ID NOs shown: 4, 9, 10, 24, 25 and 94.

In FIG. 7A and 7B show humanized sequences for the VL region of mouse monoclonal antibody 141A. SEQ ID NOs shown: 5, 10, 11, 26, 27 and 94.

In FIG. 8A and 8B show humanized sequences for the VL region of the mouse monoclonal antibody 175A. SEQ ID NOs shown: 6, 9, 10, 28, 29 and 94.

In FIG. 9 shows the pseudo-sequences of the VH and VL domains of mouse monoclonal antibodies 76E1, 141A and 175A (SEQ ID NO: 1143-1148). CDRs are indicated in bold.

In FIG. 10 shows that treatment with anti-C10orf54 antibody causes potent inhibition of tumor growth in established Kasumi-3 tumors.

In FIG. 11 shows that treatment with the murine anti-C10orf54 antibody 175A causes potent inhibition of tumor growth in established Kasumi-3 tumors.

In FIG. 12 shows the results of a secondary ADC assay using anti-C10orf54 antibodies in a cell viability assay using a C10orf54-expressing sarcoma line.

In FIG. 13 and 14 show the activity of unconjugated and MMAF-conjugated anti-C10orf54 antibodies in a cell viability assay using C10orf54-expressing sarcoma lines and a parental sarcoma line.

In FIG. 15 shows the results of treatment with unconjugated and MMAF-conjugated anti-C10orf54 antibodies in a tumor model using a C10orf54-expressing sarcoma line and a parental sarcoma line.

In FIG. 16A and 16B show a sequence alignment of the heavy chain variable regions and light chain variable regions of murine anti-C10orf54 antibodies designated 76E1, 141A and 175A (SEQ ID NOs: 1-6). CDR boundaries are indicated according to Kabat, AbM, Chothia, Contact and IMGT numbering.

In FIG. 17A and 17B show a sequence alignment of the heavy chain variable regions and the light chain variable regions of representative humanized C10orf54 antibodies, designated hu76E1, hu141A, and hu175A (SEQ ID NO: 1135-1137 for heavy chains; SEQ ID NO: 1139-1141 for light chains) , and the corresponding consensus sequences between hu76E1 and hu175A (SEQ ID NO: 1138 for the heavy chain; SEQ ID NO: 1142 for the light chain). Residues listed immediately below the aligned sequences indicate specific residues that may vary higher up in the “X” positions in the consensus sequence.

In FIG. 18A-18D show alignments of the VH and VL sequences of the antibodies described herein by paratope group. SEQ ID NOs: 1271-1280 for VH and VL are shown. Also shown are SEQ ID NOs: 1291, 1306, 1441, 1918, 1440, 1368, 1442, 1919, 1385, 1405, 1446, 1920, 1443, 1458, 1446, 1921, 1473, 1445, 1447, 1922, 1444, 1508, 1448 and 1923 for consensus CDR sequences within paratope groups.

In FIG. 19 shows representative human germline antibody sequences for humanizing the anti-C10orf54 antibodies described herein.

In FIG. 20A and 20B show selected human antibody VH and VL sequences for humanizing the anti-C10orf54 antibodies described herein.

SEQ ID NOs shown: 7, 1902-1904, 1907, 1905, 1906, 1912, 1910, 11, 1909, 1913 (in order from top to bottom) for VH and VL sequences.

In FIG. 21A shows a graphical representation of the C10orf54 protein and chimeric protein constructs. The designation "man" refers to the CC1 design; "mouse" refers to the CC2 design; "hsIGVmmSTALK" refers to the CC5 design; "mmIGVhsSTALK" refers to the CC6 design; "hsABCmmC10" refers to the CC7 design; “mmabChsC10” refers to the CC8 construct; "hsC10mmLOOP" refers to the CC9 design; and "mmC10hsLOOP" refers to the CC10 construct as described in Example 3. Also depicted are the amino acid sequence alignment results for human C10orf54 (residues 1-193 in SEQ ID NO: 1079) and mouse C10orf54 (residues 1-190 in SEQ ID NO: 1243 ), including these residues in the consensus sequence (SEQ ID NO: 1914).

In FIG. 21B shows a phylogenetic tree for antibodies to C10orf54 for both VH and VL genes, including paratope subgroup distribution and flow cluster analysis as described in Example 3. The designation “human full-length protein” refers to construct CC1; "rat" refers to the CC3 design; “full-length cynomolgus protein” refers to construct CC4; "hsIGVmmSTALK" refers to the CC5 design; "hsABCmmC10" refers to the CC7 design; "mmABChsC10" refers to the CC8 design; "hsC10mmLOOP" refers to the CC9 design; and "mmC10hsLOOP" refers to the CC10 design as described in Example 3.

In FIG. 22A and 22B show humanized sequences for the VH and VL regions of mouse monoclonal antibody 26A, respectively. SEQ ID NO: 1902, 82, 1266 and 1529-1531 are depicted in FIG. 22A, and SEQ ID NOs: 1910, 94 and 1532-1534 are depicted in FIG. 22V. The humanized VH, designated h26AH1, and the humanized VL, designated h26AL1, are each “CDR-swap” constructs without any changes in the human antibody framework region. The following sequences contain altered amino acid residues. # indicates a substitution that prevents deamidation: Q/S/A/D.

In FIG. 23A and 23B show humanized sequences for the VH and VL regions of mouse monoclonal antibody 128A, respectively. SEQ ID NOs: 1902, 82, 1258 and 1535-1537 are depicted in FIG. 23A, and SEQ ID NOs: 1907, 94, 1259 and 1538-1540 are depicted in FIG. 23V. The humanized VH, designated h128AH1, and the humanized VL, designated M28AL1, are each “CDR replacement” constructs without any changes in the human antibody framework region. The following sequences contain altered amino acid residues. # indicates a substitution that prevents deamidation: Q/S/A/D.

In FIG. 24A and 24B show humanized sequences for the VH and VL regions of mouse monoclonal antibody 124A, respectively. SEQ ID NO: 1902, 82, 1281, 1541 and 1542 are shown in FIG. 24A, and SEQ ID NOs: 1911, 94, 1282, 1546 and 1547 are depicted in FIG. 24V. The humanized VH, designated h124AH1, and the humanized VL, designated h124AL1, are each “CDR replacement” constructs without any change in the human antibody framework region. The following sequences contain altered amino acid residues. # indicates a substitution that prevents deamidation: Q/S/A/D.Q/S/A/D. @ indicates substitutions that prevent the formation of isoaspartic acid: Q/S/A.

In FIG. 25A and 25B show humanized sequences for the VH and VL regions of mouse monoclonal antibody 259A, respectively. SEQ ID NO: 1902, 82, 1275 and 1543-1545 are shown in FIG. 25A, SEQ ID NOs: 1905, 94, 1276, 1548 and 1549 are depicted in FIG. 25V. The humanized VH, designated h259AH1, and the humanized VL, designated h259AL1, are each “CDR replacement” constructs without any change in the human antibody framework region. The following sequences contain altered amino acid residues. # indicates a substitution that prevents deamidation: Q/S/A/D. @ indicates substitutions that prevent the formation of isoaspartic acid: E/S/A.

In FIG. 26A and 26B show expression of C10orf54 in MDSC subsets. In FIG. 26A shows the percentage of C10orf54 in Lin ^- /CD11b ⁺ MDSC subpopulations. In FIG. 26B shows the copy number of C10orf54 for Lin ^- /CD11b ⁺ MDSC subpopulations. MDSC populations are referred to as monocyte (CD14 ⁺ /HLA ^- DR ^- ), granulocytic (CD15 ⁺ /HLA ^- DR ^- ) and immature myeloid cells (CD15 ^- /HLA ^- DR ^- ).

In FIG. 27 shows a scatter plot of data for C10orf54 expression in PBMC (peripheral blood mononuclear cells) for subgroups of patients with non-small cell lung cancer (NSCLC).

In FIG. 28 shows histograms of T cell proliferation inhibited by the C10orf54-Fc construct. The incorporation of ³ H-thymidine is shown.

In FIG. 29 shows histograms demonstrating the ability of anti-C10orf54 antibodies to attenuate C10orf54-mediated suppression of naïve T cell proliferation and cytokine secretion.

In FIG. 30A-30C show a comparison of naïve and pan T cell populations. T cells at a rate of 50,000 cells per well were grown in plates precoated with anti-CD3 antibody at a concentration of 5 μg/ml and in the presence of C10orf54-Fc at various concentrations. The cells were then co-stimulated using anti-CD28 antibody (αCD28) at various concentrations (no anti-CD3 antibody was added to control wells (αCD28 concentration was 0 μg/ml)). Values are average relative luminescence units (RLU)/well (n=4). In FIG. Figure 30A shows pan T cells 2 days after stimulation. In FIG. 30B shows naïve T cells 2 days after stimulation. In FIG. 30C shows naïve T cells 3 days after stimulation.

DETAILED DESCRIPTION

The present invention provides antibodies that bind to C10orf54, including a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope. Such antibodies include humanized anti-C10orf54 antibodies. Also provided are antibodies (eg, humanized anti-C10orf54 antibodies) that competitively block the binding of the anti-C10orf54 antibody provided herein to the C10orf54 polypeptide. Anti-C10orf54 antibodies (eg, humanized anti-C10orf54 antibodies) provided herein may also be conjugated or recombinantly fused to a diagnostic agent, detection agent, or therapeutic agent (eg, to form an antibody-drug conjugate). In addition, compositions containing an antibody to C10orf54 (for example, a humanized antibody to C10orf54) are provided. For example, the detectable agent may be a detectable probe.

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC10 (SEQ ID NO: 1251), and does not bind to the second group of proteins or chimeric C10orf54 proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248) and CC9 (SEQ ID NO: 1250).

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246) and CC8 (SEQ ID NO: 1249), and does not bind to the second group of proteins or C10orf54 chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251). In some aspects, such an antibody does not contain one or more CDR sequences selected from the group consisting of 30, 1099, 1104, 1105, 1110, 31, 1100, 1106, 1111, 1116, 32, 1101, 1107, 1112, 45, 1102, 1108, 1113, 40, 1103, 1114, 41, 1109 and 1115.

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), and CC5 (SEQ ID NO: 1246), and does not bind to the second group of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC8 (SEQ ID NO: 1249), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251). In some aspects, such an antibody does not contain one or more CDR sequences selected from the group consisting of 36, 1081, 1086, 1087, 1092, 37, 1082, 1088, 1093, 1098, 38, 1083, 1089, 1094, 45, 1084, 1090, 1095, 46, 1085, 1096, 47, 1091 and 1097.

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC9 (SEQ ID NO: 1250), and does not bind to the second group of proteins or chimeric C10orf54 proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251). In some aspects, such an antibody does not contain one or more CDR sequences selected from the group consisting of 33, 1117, 1122, 1123, 1128, 34, 1118, 1124, 1129, 1134, 35, 1119, 1125, 1130, 42, 1120, 1126, 1131, 43, 1121, 1132, 44, 1127 and 1133.

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC3 (SEQ ID NO: 1244), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC9 (SEQ ID NO: 1250), and does not bind to the second group of proteins or C10orf54 chimeric proteins designated CC2 (SEQ ID NO: 1243), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248) and CC10 (SEQ ID NO: 1251).

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC10 (SEQ ID NO: 1251), and does not bind to the second group of proteins or chimeric C10orf54 proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251).

In addition, this application provides isolated nucleic acid molecules encoding the VH chain, VL chain, VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3 antibodies to C10orf54, which bind to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope. In addition, vectors and host cells are proposed containing nucleic acid molecules encoding antibodies to C10orf54 that bind to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope. Methods for producing antibodies that bind to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope are also provided.

Methods of using antibodies to C10orf54 (for example, humanized antibodies to C10orf54) are provided. The methods include treating, preventing, or alleviating a disease, disorder, or condition, including one or more symptoms of the disease, disorder, or condition, and involves administering a therapeutically effective amount of an anti-C10orf54 antibody, including an antibody-drug conjugate (ADC) containing the anti-C10orf54 antibody provided herein to a subject, thereby treating, preventing, or alleviating a disease, disorder, or condition, including one or more symptoms of the disease, disorder, or condition. In some embodiments, anti-C10orf54 antibodies are humanized antibodies that bind to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope. In one embodiment, the disease, disorder, or condition is caused by or otherwise associated with C10orf54, including caused by or associated with C10orf54-expressing cells (eg, tumor cells, myeloid-derived suppressor cells (MDSCs), suppressive dendritic cells (suppressive dendritic cells) DC) and/or regulatory T cells (T _reg )). In certain embodiments, the disease is a cancer, such as leukemia, bladder cancer, skin cancer, colon cancer, breast cancer, liver cancer, kidney cancer, lung cancer, gastric cancer, pancreatic cancer, esophageal cancer, or fibrosarcoma. In one embodiment, the leukemia is acute myeloid leukemia (AML). In other embodiments, the disease is graft-versus-host disease (GVHD). Additional proposed methods include the use of an anti-C10orf54 antibody provided herein that has C10orf54-binding activity in the case of C10orf54-expressing cells, for example, in the form of an unconjugated antibody or an antibody conjugated (ADC), including for the inhibition and/or destruction of C10orf54- expressing cells (eg, antibodies with antitumor activity to mediate an antitumor effect). In certain embodiments, anti-C10orf54 antibodies, including ADCs containing anti-C10orf54 antibodies provided herein, inhibit C10orf54-mediated T cell suppressive activity (eg, allowing an effective antitumor immune response). In certain embodiments, the anti-C10orf54 antibodies provided herein directly kill C10orf54-expressing cells (e.g., C10orf54-bearing tumor cells, myeloid-derived suppressor cells (MDSCs), suppressive dendritic cells (DC suppressive cells), and/or regulatory T cells (T _reg )), for example, through the manifestation of antibody-dependent cellular cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC). In certain embodiments, antibody-drug conjugates (ADCs) containing anti-C10orf54 antibodies provided herein directly kill C10orf54-expressing cells, including by binding to C10orf54-expressing cells (e.g., tumor cells, myeloid-derived suppressor cells (MDSCs) ), suppressive dendritic cells (DC suppressive) and/or regulatory T cells ( _Treg )), for example, allowing internalization of a cytotoxic drug. In any of the above embodiments, the anti-C10orf54 antibody may be a humanized anti-C10orf54 antibody as provided herein that binds to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope. In any of the above embodiments, the anti-C10orf54 antibody may be a humanized anti-C10orf54 antibody as provided herein that binds to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope.

Additional methods of using the antibody to C10orf54 have been proposed.

These methods include methods of inhibiting cell growth and/or killing cells capable of expressing C10orf54 on the surface, comprising contacting the cells with an effective amount of an anti-C10orf54 antibody or antibody-drug conjugates provided herein. In one embodiment, the cell is a regulatory T cell (eg, a CD4 ⁺ Foxp3 ⁺ regulatory T cell). In other embodiments, the cell is a myeloid suppressor cell (eg, CD11b ⁺ or CD11b ^high myeloid suppressor cell) or a suppressive dendritic cell (eg, CD11b ⁺ or CD11b ^high dendritic cell). In other embodiments, the cell is a cancerous or precancerous cell. Additional proposed methods include the use of an anti-C10orf54 antibody provided herein that has C10orf54-binding activity in the case of C10orf54-expressing cells, for example, in the form of an unconjugated antibody or an antibody conjugated (ADC), including for the inhibition and/or destruction of C10orf54- expressing cells (eg, antibodies with antitumor activity to mediate an antitumor effect). In certain embodiments, anti-C10orf54 antibodies, including ADCs containing anti-C10orf54 antibodies provided herein, inhibit C10orf54-mediated T cell suppressive activity (eg, allowing an effective antitumor immune response). In certain embodiments, the anti-C10orf54 antibodies provided herein directly kill C10orf54-expressing cells (e.g., C10orf54-bearing tumor cells, myeloid-derived suppressor cells (MDSCs), suppressive dendritic cells (DC suppressive cells), and/or regulatory T cells (T _reg )), for example, through the manifestation of antibody-dependent cellular cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC). In certain embodiments, antibody-drug conjugates (ADCs) containing anti-C10orf54 antibodies provided herein directly kill C10orf54-expressing cells, including by binding to C10orf54-expressing cells (e.g., tumor cells, myeloid-derived suppressor cells (MDSCs) ), suppressive dendritic cells (DC suppressive) and/or regulatory T cells ( _Treg )), for example, allowing internalization of a cytotoxic drug. In any of the above embodiments, the anti-C10orf54 antibody may be a humanized anti-C10orf54 antibody as provided herein that binds to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope.

These methods include methods of modulating an immune response in a subject, comprising administering an effective amount of an anti-C10orf54 antibody (eg, a humanized anti-C10orf54 antibody) provided herein to the subject. In one embodiment, modulation includes enhancing T cell activation. In another embodiment, the modulation includes enhancing T cell proliferation. In another embodiment, modulation includes increasing the production of cytokines.

These methods include methods for detecting C10orf54 in a sample, comprising contacting the sample with an anti-C10orf54 antibody (eg, a humanized anti-C10orf54 antibody) provided herein, such as an antibody that contains a detectable agent. In certain embodiments, the sample contains a cell expressing C10orf54 on its surface.

These methods include methods of treating cancer diseases comprising administering to a subject an anti-C10orf54 antibody or an antibody-drug conjugate (ADC) containing an anti-C10orf54 antibody (e.g., an ADC of the formula AL-CTX, wherein A is an antibody, L is a linker, and CTX is a cytotoxic agent) in a therapeutically effective amount, including an amount effective to kill a C10orf54-expressing cell (eg, a tumor cell, a myeloid suppressor cell (MDSC), a dendritic cell suppressor (DC suppressor), and/or regulatory T cell (T _reg )). In some embodiments, the cancer is acute myeloid leukemia (AML). In any of the above embodiments, the anti-C10orf54 antibody may be a humanized anti-C10orf54 antibody as provided herein that binds to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope.

These methods include methods of killing C10orf54-expressing cells (eg, tumor cells, myeloid suppressor cells (MDSCs), dendritic cell suppressors (DC suppressors), and/or T regulatory cells ( _Treg )), comprising contacting A C10orf54-expressing cell (eg, a tumor cell, a myeloid suppressor cell (MDSC), a suppressive dendritic cell (DC suppressive), and/or a regulatory T cell (T _reg )) with an anti-C10orf54 antibody or antibody-drug conjugate (ADC) containing an antibody to C10orf54 (for example, an ADC of the formula AL-CTX, where A is an antibody, L is a linker, and CTX is a cytotoxic agent), in an amount effective to kill a given cell (for example, a tumor cell, myeloid suppressor cell (MDSC), which has a suppressive effect on a dendritic cell (which has a suppressive effect on DC) and/or a regulatory T cell (T _reg )). In some embodiments, the tumor cell is an AML cell. In any of the above embodiments, the anti-C10orf54 antibody may be a humanized anti-C10orf54 antibody as provided herein that binds to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope.

In one embodiment, this application provides a kit containing an anti-C10orf54 antibody (eg, a humanized anti-C10orf54 antibody) that binds to a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope as provided herein. In some embodiments, the kits contain an antibody-drug conjugate (ADC), where the antibody is an anti-C10orf54 antibody (eg, a humanized anti-C10orf54 antibody).

ANTIBODIES

In some embodiments, this application provides antibodies that bind to C10orf54, including a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope. In some embodiments, anti-C10orf54 antibodies are humanized antibodies that bind to C10orf54, including a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, or a C10orf54 epitope.

In certain embodiments, the anti-C10orf54 antibody comprises the VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and/or VL CDR3 of mouse monoclonal antibodies 5B, 46A, 97A, 128A, 146C, 208A, 215A , 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, as listed in Table 2 and depicted in FIG. 3-8, 22A, 22B, 23A, 23B, 24A, 24B, 25A and 25B. Accordingly, in some aspects, the VH domain contains the amino acid sequence of SEQ ID NO: 1. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 2. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 3. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1252. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1254. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1256. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1256. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1258. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1260. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1262. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1262. The -domain contains the amino acid sequence of SEQ ID NO: 1266. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1268. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1271. In some embodiments, the VH domain contains contains the amino acid sequence of SEQ ID NO: 1273. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1375. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1277. In some embodiments, the VH domain contains the amino acid sequence the sequence of SEQ ID NO: 1279. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1281. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1283. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1285. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1287. In some embodiments, the VH domain contains the amino acid sequence of SEQ ID NO: 1289. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 4. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 5. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 6. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1253. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1255. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1257. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1259. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1261. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1263. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1265. In some In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1267. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1269. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1270. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1270. The -domain contains the amino acid sequence of SEQ ID NO: 1272. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1274. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1276. In some embodiments, the VL domain contains contains the amino acid sequence of SEQ ID NO: 1278. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1280. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1282. In some embodiments, the VL domain contains the amino acid sequence the sequence of SEQ ID NO: 1284. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1286. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1288. In some embodiments, the VL domain contains the amino acid sequence of SEQ ID NO: 1290.

In certain embodiments, the anti-C10orf54 antibody comprises VH FR1, VH FR2, VH FR3, VH FR4, VL FR1, VL FR2, VL FR3 and/or VL FR4 from a human germline immunoglobulin amino acid sequence or variant thereof. For example, in some embodiments, the anti-C10orf54 antibody comprises VH FR1, VH FR2, VH FR3, and/or VH FR4 depicted in the human germline immunoglobulin sequence identified in Table 3. Accordingly, in some embodiments, the anti-C10orf54 antibody comprises VH FR1, VH FR2 , VH FR3 and/or VH FR4 from the human germline IGHV1-18 (SEQ ID NO: 7) and IGHJ4-01 (SEQ ID NO: 82). In some embodiments, the anti-C10orf54 antibody comprises VH FR1, VH FR2, VH FR3 and/or VH FR4 from the human germline IGHV3-48 (SEQ ID NO: 8) and IGHJ4-01 (SEQ ID NO: 82). In some embodiments, the anti-C10orf54 antibody comprises human germline VH FR1, VH FR2, VH FR3 and/or VH FR4 IGHV1-46*01 (SEQ ID NO: 1902) and IGHJ4-01 (SEQ ID NO: 82). In some embodiments, the anti-C10orf54 antibody comprises human germline VH FR1, VH FR2, VH FR3 and/or VH FR4 IGHV3-74*01 (SEQ ID NO: 1903) and IGHJ4-01 (SEQ ID NO: 82). In some embodiments, the anti-C10orf54 antibody comprises human germline VH FR1, VH FR2, VH FR3 and/or VH FR4 IGHV4-61*01 (SEQ ID NO: 1904) and IGHJ4-01 (SEQ ID NO: 82). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV2-28 (SEQ ID NO: 9) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV1-39 (SEQ ID NO: 10) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV3-20 (SEQ ID NO: 10) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGHV1-46*01 (SEQ ID NO: 1920) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGHV3-74*01 (SEQ ID NO: 1903) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGHV4-61*01 (SEQ ID NO: 1904) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV2-28*01 (SEQ ID NO: 1905) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV2-29*02 (SEQ ID NO: 1906) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV1-39*01 (SEQ ID NO: 1907) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV3-20*01 (SEQ ID NO: 1908) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV3D-20*01 (SEQ ID NO: 1909) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV3-11*01 (SEQ ID NO: 1910) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV2-30*01 (SEQ ID NO: 1911) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV2-30*02 (SEQ ID NO: 1912) and IGKJ2-1 (SEQ ID NO: 94). In some embodiments, the anti-C10orf54 antibody comprises human germline VL FR1, VL FR2, VL FR3 and/or VL FR4 IGKV4-1*01 (SEQ ID NO: 1913) and IGKJ2-1 (SEQ ID NO: 94).

In certain embodiments, antibodies that bind to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contain a VH domain having the amino acid sequence identified in Table 4 or FIG. 3-8, 22A, 22B, 23A, 23B, 24A, 24B, 25A or 25B, and/or a VL domain having the amino acid sequence identified in Table 4 or FIG. 3-8, 22A, 22B, 23A, 23B, 24A, 24B, 25A or 25B.

Accordingly, in some embodiments, antibodies that bind to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contain a VH domain having the amino acid sequence of SEQ ID NO: 20, 21, 22, 23, 1529-1531 , 1535-1537 or 1541-1545, and/or a VL domain having the amino acid sequence of SEQ ID NO: 28, 29, 1532-1534, 1538-1540 or 1546-1549. In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH domain having the amino acid sequence of SEQ ID NO: 20 and/or a VL domain having the amino acid sequence with SEQ ID NO: 28. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH domain having the amino acid sequence of SEQ ID NO: 21, and/ or a VL domain having the amino acid sequence of SEQ ID NO: 28. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a C10orf54 polypeptide fragment, a C10orf54 epitope) contains a VH domain having the amino acid sequence of SEQ ID NO: 22, and/or a VL domain having the amino acid sequence of SEQ ID NO: 28. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains A VH domain having the amino acid sequence of SEQ ID NO: 23, and/or a VL domain having the amino acid sequence of SEQ ID NO: 28. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide fragment polypeptide C10orf54, epitope C10orf54), contains a VH domain having the amino acid sequence of SEQ ID NO: 20, and/or a VL domain having the amino acid sequence of SEQ ID NO: 29. In one aspect, an antibody that binds to C10orf54 (eg, with a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope), contains a VH domain having the amino acid sequence of SEQ ID NO: 21, and/or a VL domain having the amino acid sequence of SEQ ID NO: 29. According to one of aspects, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH domain having the amino acid sequence of SEQ ID NO: 22 and/or a VL domain having the amino acid sequence of SEQ ID NO: 29. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH domain having the amino acid sequence of SEQ ID NO: 23, and/or VL -domain having the amino acid sequence of SEQ ID NO: 29.

In some embodiments, antibodies that bind to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contain a VH domain having the amino acid sequence of SEQ ID NO: 12, 13, 14, or 15, and/or VL- domain having the amino acid sequence of SEQ ID NO: 24 or 25. Accordingly, in one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a C10orf54 polypeptide fragment, a C10orf54 epitope) contains a VH domain having the amino acid sequence with SEQ ID NO: 12, and/or a VL domain having the amino acid sequence of SEQ ID NO: 24. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH domain having the amino acid sequence of SEQ ID NO: 13, and/or a VL domain having the amino acid sequence of SEQ ID NO: 24. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide fragment of the C10orf54 polypeptide, the C10orf54 epitope), contains a VH domain having the amino acid sequence of SEQ ID NO: 14, and/or a VL domain having the amino acid sequence of SEQ ID NO: 24. In one aspect, an antibody that binds to C10orf54 (eg, with a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope), contains a VH domain having the amino acid sequence of SEQ ID NO: 15, and/or a VL domain having the amino acid sequence of SEQ ID NO: 24. According to one In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH domain having the amino acid sequence of SEQ ID NO: 12, and/or a VL domain having the amino acid sequence of SEQ ID NO: 25. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH domain having the amino acid sequence of SEQ ID NO: 13, and/or A VL domain having the amino acid sequence of SEQ ID NO: 25. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH domain having the amino acid sequence of SEQ ID NO: 14, and/or a VL domain having the amino acid sequence of SEQ ID NO: 25. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orF54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH -domain having the amino acid sequence of SEQ ID NO: 15, and/or a VL domain having the amino acid sequence of SEQ ID NO: 25.

In some embodiments, antibodies that bind to C10orf54 (e.g., a C10orF54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contain a VH domain having the amino acid sequence of SEQ ID NO: 16, 17, 18, or 19, and/or VL- domain having the amino acid sequence of SEQ ID NO: 26 or 27. Accordingly, in one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a C10orf54 polypeptide fragment, a C10orf54 epitope) contains a VH domain having the amino acid sequence with SEQ ID NO: 16, and/or a VL domain having the amino acid sequence of SEQ ID NO: 26. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH domain having the amino acid sequence of SEQ ID NO: 17, and/or a VL domain having the amino acid sequence of SEQ ID NO: 26. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide fragment of the C10orf54 polypeptide, the C10orf54 epitope), contains a VH domain having the amino acid sequence of SEQ ID NO: 18, and/or a VL domain having the amino acid sequence of SEQ ID NO: 26. In one aspect, an antibody that binds to C10orf54 (eg, with a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope), contains a VH domain having the amino acid sequence of SEQ ID NO: 19, and/or a VL domain having the amino acid sequence of SEQ ID NO: 26. According to one In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH domain having the amino acid sequence of SEQ ID NO: 16, and/or a VL domain having the amino acid sequence of SEQ ID NO: 27. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH domain having the amino acid sequence of SEQ ID NO: 17, and/or A VL domain having the amino acid sequence of SEQ ID NO: 27. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH domain having the amino acid sequence of SEQ ID NO: 18, and/or a VL domain having the amino acid sequence of SEQ ID NO: 27. In one aspect, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH -domain having the amino acid sequence of SEQ ID NO: 19, and/or a VL domain having the amino acid sequence of SEQ ID NO: 27.

In some embodiments, antibodies provided herein that bind to the C10orf54 epitope contain a VH region with VH CDR1, VH CDR2 and/or VH CDR3 that have the amino acid sequence identified in Tables 5-11 or Tables 12-33 below ; and/or a VL region with VL CDR1, VL CDR2 and/or VL CDR3, which have the amino acid sequence identified in Tables 5-11 or Tables 12-33 below.

In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 36 ; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 37; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38. In certain embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47. In other embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 6. In another embodiment, the antibody further comprises a VL region having amino acid sequence of SEQ ID NO: 28. In further embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 29. In some embodiments, the antibody comprises (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 36; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 37; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47. It is intended that to the extent that an antibody of this invention is an antibody that “binds the C10orf54 epitope,” such antibodies also bind the polypeptide C10orf54, a polypeptide fragment or their antigen.

In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 36 ; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 50; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38. In certain embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47. In other embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 6. In another embodiment, the antibody further comprises a VL region having amino acid sequence of SEQ ID NO: 28. In further embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 29. In some embodiments, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 36; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 50; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47.

In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 36 ; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 99; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38. In certain embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47. In other embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 6. In another embodiment, the antibody further comprises a VL region having amino acid sequence of SEQ ID NO: 28. In further embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 29. In some embodiments, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 36; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 99; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47.

In another embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47. In some embodiments, the antibody further comprises a VH region having the amino acid sequence of SEQ ID NO: 20. In another embodiment, the antibody further comprises a VH region having the amino acid sequence of SEQ ID NO: 21. In other embodiments, the antibody further comprises a VH region having the amino acid sequence of SEQ ID NO: 22. In other embodiments, the antibody further comprises a VH region having the amino acid sequence of SEQ ID NO: 23 .

In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 30 ; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 31; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 32. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41. In other embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 24. In another embodiment, the antibody further comprises a VL region having amino acid sequence of SEQ ID NO: 25. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 30; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 31; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 32; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41.

In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 30 ; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 321; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 32. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41. In other embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 24. In another embodiment, the antibody further comprises a VL region having amino acid sequence of SEQ ID NO: 25. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 30; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 321; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 32; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41.

In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 30 ; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 835; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 32. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41. In other embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 24. In another embodiment, the antibody further comprises a VL region having amino acid sequence of SEQ ID NO: 25. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 30; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 835; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 32; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41.

In some embodiments, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41. In some embodiments, the antibody further comprises a VH region having the amino acid sequence of SEQ ID NO: 12. In another embodiment, the antibody further comprises a VH region having the amino acid sequence of SEQ ID NO: 13. In other embodiments, the antibody further comprises a VH region having the amino acid sequence of SEQ ID NO: 14. In other embodiments, the antibody further comprises a VH region having the amino acid sequence of SEQ ID NO: 15 .

In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 33 ; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 34; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 42; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 43; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44. In other embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 26. In another embodiment, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 27. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 33; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 34; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 35; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 42; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 43; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44.

In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 33 ; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 49; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 42; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 43; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44. In other embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 26. In another embodiment, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 27. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 33; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 49; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 35; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 42; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 43; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44.

In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 33 ; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1070; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 42; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 43; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44. In other embodiments, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 26. In another embodiment, the antibody further comprises a VL region having the amino acid sequence of SEQ ID NO: 27. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 33; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1070; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 35; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 42; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 43; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44.

As will be appreciated by one skilled in the art, the boundaries between CDRs and framework sequences for any of the VH regions and VL regions described herein can be determined using any of the methods well known in the art, including IMGT, according to Kabat , Chothia, "contact" method, ABM or Kabat plus Chothia (eg, according to the "Typical System" as set forth herein). Accordingly, any anti-C10orf54 antibody having one or more CDR or framework sequences described herein includes a CDR or framework amino acid sequence as determined by IMGT, IMGT, Kabat, Chothia, Contact, AbM, or Kabat plus Chothia. For example, exemplary CDR sequences for both the VH and VL regions that may be included in an anti-C10orf54 antibody of the invention are shown in Tables 12-33 (also see, eg, Tables 5-11).

In certain embodiments, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: a VH region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 30, 33, 36, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335 and 1717-1720; (2) VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 31, 34, 37, 849, 1082, 1088, 1092, 1093, 1098, 1100, 1106, 1111, 1118, 1124, 1129, 1134, 1161, 1336-1344, 1348-1384, 1556-1559, 1829-1847 and 1917; and (3) VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 32, 35, 38, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 and 1385-1424.

In certain embodiments, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises: a VL region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 42, 45, 253-271, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 and 1915; (2) VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 40, 43, 46, 157, 843-846, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526- 1528, 1630-1633, 1685-1688 and 1898-1900; and (3) VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 41, 44, 47, 1091, 1097, 1109, 1115, 1127, 1133 and 1493-1525.

In certain embodiments, the antibody comprises (a) a VH region comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 30, 33, 36, 1081, 1086, 1087, 1092, 1099 , 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335 and 1717-1720; (2) VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 31, 34, 37, 849, 1082, 1088, 1092, 1093, 1098, 1100, 1106, 1111, 1118, 1124, 1129, 1134, 1161, 1336-1344, 1348-1384, 1556-1559, 1829-1847 and 1917; and (3) VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 32, 35, 38, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 and 1385-1424; and (b) a VL region comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 42, 45, 253-271, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 and 1915; (2) VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 40, 43, 46, 157, 843-846, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526- 1528, 1630-1633, 1685-1688 and 1898-1900; and (3) VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 41, 44, 47, 1091, 1097, 1109, 1115, 1127, 1133 and 1493-1525.

It is intended that to the extent that an antibody of this invention is an antibody that “binds to a C10orf54 epitope,” such antibodies also bind to a C10orf54 polypeptide, a polypeptide fragment, or an antigen thereof.

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CCS (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC10 (SEQ ID NO: 1251), and does not bind to the second group of proteins or chimeric C10orf54 proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248) and CC9 (SEQ ID NO: 1250). In some aspects, the antibody comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 30, 1099, 1104, 1105, 1110 , 1291-1305, 1311-1315 and 1321-1325; (2) VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 37, 849, 1082, 1088, 1093, 1098, 1336-1344, 1348-1367, 1373, 1374 and 1556-1559; and (3) VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 38, 1083, 1089, 1094, 1385-1404 and 1409-1412; and/or (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 45, 1102, 1108, 1113, 1425-1430, 1432- 1457, 1681-1684 and 1915; (2) VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 40, 157, 1103, 1114, 1473-1481, 1526-1528, 1630-1633 and 1685-1688; and (3) VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1493-1507, 1511-1516 and 1523-1525. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1291, 1292, 1293, 1294, or 1295; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1336, 1337, 1338, 1339 or 1340; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1385, 1386, 1387 or 1388; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1425, 1426, 1427 or 1428; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1473, 1474 or 1475; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1493, 1494, or 1495. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO : 1291, 1292, 1293, 1294 or 1295; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1341, 1342, 1338, 1343 or 1344; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1389, 1390, 1391 or 1392; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1425, 1426, 1427 or 1428; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1473, 1474 or 1475; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1496, 1497, or 1498. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO : 1291, 1292, 1293, 1294 or 1295; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1348, 1337, 1338, 1349 or 1350; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1385, 1386, 1387 or 1388; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1429, 1426, 1427, 1430, 1681, 1682, 1683 or 1684; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1473, 1474, 1475, 1685, 1686, 1687 or 1688; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1493, 1494, or 1495. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO : 1291, 1292, 1293, 1294 or 1295; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1348, 1337, 1338, 1349 or 1350; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1385, 1386, 1387 or 1388; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1429, 1426, 1427 or 1430; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1473, 1474 or 1475; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1493, 1494, or 1495. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO : 1291, 1292, 1293, 1294 or 1295; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1351, 1337, 1338, 1352 or 1353; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1385, 1386, 1387 or 1388; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1425, 1426, 1427 or 1428; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1473, 1474 or 1475; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1493, 1494, or 1495. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO : 30, 1099, 1104, 1105 or 1110; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1359, 1360, 1361, 1362 or 1363; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1397, 1398, 1399 or 1400; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1437, 1451, 1438, 1452, 1451, 1439, 1453, 1450, or 1915; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1526, 1479, 1527, 1480, 157, 1528 or 1481; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1523, 1502, 1524, 1503, 1525, or 1504. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having amino acid sequence of SEQ ID NO: 1301, 1302, 1303, 1304 or 1305; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1364, 1365, 1361, 1366 or 1367; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1401, 1402, 1403 or 1404; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1454, 1455, 1456 or 1457; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40, 1103 or 1114; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1505, 1506, or 1507. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO : 1311, 1312, 1313, 1314 or 1315; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 37, 1082, 1088, 1093 or 1098; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1409, 1410, 1411 or 1412; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45, 1102, 1108 or 1113; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40, 1103 or 1114; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1511, 1512, or 1513. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO : 1321, 1322, 1323, 1324 or 1325; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 849, 1082, 1088, 1373 or 1374; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38, 1083, 1089 or 1094; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45, 1102, 1108 or 1113; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40, 1103 or 1114; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1514, 1515 or 1516.

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CCS (SEQ ID NO: 1246) and CC8 (SEQ ID NO: 1249), and does not bind to the second group of proteins or C10orf54 chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251). In some aspects, such an antibody does not contain one or more CDR sequences selected from the group consisting of 30, 1099, 1104, 1105, 1110, 31, 1100, 1106, 1111, 1116, 32, 1101, 1107, 1112, 45, 1102, 1108, 1113, 40, 1103, 1114, 41, 1109, and 1115. In some aspects, the antibody comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 30, 1099, 1110, 1104, 1105, 1296-1300, 1306-1310, 1316-1320 and 1717-1720; (2) VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 31, 37, 1082, 1088, 1092, 1098, 1100, 1106, 1111, 1116, 1354-1358, 1368-1372, 1829- 1847 and 1917; and (3) VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 32, 38, 1083, 1089, 1094, 1101, 1107, 1112, 1393-1396, 1405-1408, 1413, 1414; and/or (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 45, 253-271, 1102, 1108, 1113, 1431- 1434, 1458-1465, 1744-1822, 1878-1896; (2) VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 40, 843-846, 1103, 1114, 1476-1478, 1482-1487, 1898-1900; and (3) VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 41, 1109, 1115, 1499-1501, 1508-1513. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1296, 1297, 1298, 1299, or 1300; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1354, 1355, 1356, 1357 or 1358; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1393, 1394, 1395 or 1396; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1431, 1432, 1433 or 1434; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1476, 1477 or 1478; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1499, 1500, or 1501. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO : 1306, 1307, 1308, 1309 or 1310; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1368, 1369, 1370, 1371 or 1372; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1405, 1406, 1407 or 1408; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1458, 1459, 1460 or 1461; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1482, 1483 or 1484; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1508, 1509, or 1510. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO : 1306, 1307, 1308, 1309 or 1310; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1368, 1369, 1370, 1371, 1372, 1829, 1830, 1831, 1832, 1833, 1834, 1835, 1836, 1837, 1838, 1840, 1841, 1842, 1843, 1844, 1845, 1846 or 1847; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1405, 1406, 1407 or 1408; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1458, 1459, 1460, 1461, 1878, 1879, 1880, 1881, 1882, 1883, 1884, 1885, 1886, 1887, 1888, 1889, 1890, 1891, 1892, 1893, 1894, 1895 or 1896; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1485, 1486, 1487, 1897, 1898, 1899 or 1900; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1508, 1509, or 1510. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO : 1316, 1317, 1318, 1319 or 1320; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 37, 1082, 1088, 1092 or 1098; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38, 1083, 1089 or 1094; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1462, 1463, 1464 or 1465; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40, 1103 or 1114; and (3) a VL CDR3 having the amino acid sequence of SEQ ID NO: 1511, 1512, or 1513. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO : 1316, 1317, 1318, 1319, 1320, 1717, 1718, 1719 or 1720; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 37, 1082, 1088, 1917 or 1098; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1413, 1414, 1089 or 1094; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1462, 1463, 1464, 1465, 1744, 45, 1745, 1746, 1747, 1748, 1749, 1750, 1751, 1752, 1753, 1754, 1755, 1756, 1757, 1758, 1759, 1760, 253, 254, 255, 256, 257, 258, 259, 1761, 1762, 1763, 1764, 1765, 6, 1767, 1768, 1769, 1770, 1771, 1772, 1773, 1774, 1775, 1776, 1777, 1778, 1779, 1780, 1781, 1782, 1783, 1784, 1785, 1786, 1787, 260, 1788, 9, 1790, 1791, 264, 268, 1792, 1793, 1794, 1795, 1796, 261, 1797, 1798, 1799, 1800, 265, 269, 1801, 1802, 1803, 1804, 1805, 262, 1806, 1807, 1808, 1809, 266, 270, 1810, 1811, 1812, 1813, 1814, 263, 1815, 1816, 1817, 1818, 267, 271, 1819, 1820, 1821 or 1822; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40, 1103, 1114, 843, 844, 846 or 845; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1511, 1512 or 1513.

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), and CC5 (SEQ ID NO: 1246), and does not bind to the second group of C10orf54 proteins or chimeric proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC8 (SEQ ID NO: 1249), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251). In some aspects, such an antibody does not contain one or more CDR sequences selected from the group consisting of 36, 1081, 1086, 1087, 1092, 37, 1082, 1088, 1093, 1098, 38, 1083, 1089, 1094, 45, 1084, 1090, 1095, 46, 1085, 1096, 47, 1091 and 1097.

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC9 (SEQ ID NO: 1250), and does not bind to the second group of proteins or chimeric C10orf54 proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251). In some aspects, such an antibody does not contain one or more CDR sequences selected from the group consisting of 33, 1117, 1122, 1123, 1128, 34, 1118, 1124, 1129, 1134, 35, 1119, 1125, 1130, 42, 1120, 1126, 1131, 43, 1121, 1132, 44, 1127, and 1133. In some aspects, the antibody comprises: (a) a heavy chain variable region (VH) comprising: (1) a VH CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 33, 1117, 1122, 1123 and 1128; (2) VH CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 34, 1082, 1088, 1118, 1124, 1129 and 1134; and (3) VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 35, 1119, 1125, 1130, 1415 and 1416; and/or (b) a light chain variable region (VL) comprising: (1) a VL CDR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 42, 1120, 1126 and 1131; (2) VL CDR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 43, 1121 and 1132; and (3) a VL CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 44, 1127, and 1133. In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having amino acid sequence of SEQ ID NO: 33, 1117, 1122, 1123 or 1128; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 34, 1082, 1088, 1129 or 1134; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 35, 1415, 1125 or 1416; and/or (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 42, 1120, 1126 or 1131; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 43, 1121 or 1132; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44, 1127 or 1133.

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC3 (SEQ ID NO: 1244), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC9 (SEQ ID NO: 1250), and does not bind to the second group of proteins or C10orf54 chimeric proteins designated CC2 (SEQ ID NO: 1243), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248) and CC10 (SEQ ID NO: 1251). In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1326, 1327, 1328, 1329, or 1330; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1375, 1376, 1377, 1378 or 1379; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1417, 1418, 1419 or 1420; and/or (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1466, 1467 or 1468; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1488, 1489 or 1490; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1517, 1518 or 1519.

In certain embodiments, the antibody provided herein binds to a first group of C10orf54 proteins or chimeric proteins, designated CC1 (SEQ ID NO: 1079), CC4 (SEQ ID NO: 1245), CC5 (SEQ ID NO: 1246), CC8 (SEQ ID NO: 1249) and CC10 (SEQ ID NO: 1251), and does not bind to the second group of proteins or chimeric C10orf54 proteins designated CC2 (SEQ ID NO: 1243), CC3 (SEQ ID NO: 1244), CC6 (SEQ ID NO: 1247), CC7 (SEQ ID NO: 1248), CC9 (SEQ ID NO: 1250) and CC10 (SEQ ID NO: 1251). In some aspects, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1331, 1332, 1333, 1334, or 1335; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1380, 1381, 1382, 1383 or 1384; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1421, 1422, 1423 or 1424; and/or (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1469, 1470, 1471 or 1472; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1491, 1488 or 1492; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1520, 1521 or 1522.

According to the amino acid sequences described in Tables 12-33, in some embodiments, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a C10orf54 polypeptide fragment, a C10orf54 epitope) contains a VH region comprising: (1) a VH CDR1 having an amino acid sequence with SEQ ID NO: 36, 1081, 1086, 1087, 1092, 30, 1099, 1104, 1105, 1110, 33, 1117, 1122, 1123, 1128 or 1291-1335; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 37, 1082, 1088, 1093, 1098, 31, 1100, 1106, 1111, 1116, 34, 1118, 1124, 1129, 1134, or 1336-1384; and/or (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38, 1083, 1089, 1094, 32, 1101, 1107, 1112, 35, 1119, 1125, 1130, or 1385-1424. In certain embodiments, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45, 1084, 1090 , 1095, 1102, 1108, 1113, 42, 1120, 1126, 1131 or 1425-1472; (2) VL CDR2 having the amino acid sequence of SEQ ID NOs: 46, 1085, 1096, 40, 1103, 1114, 43, 1121 and 1132; and/or (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47, 1091, 1097, 41, 1109, 1115, 44, 1127, 1133 or 1493-1525. In some embodiments, the antibody comprises: (a) a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 36, 1081, 1086, 1087, 1092, 30, 1099, 1104, 1105, 1110, 33 , 1117, 1122, 1123, 1128 or 1291-1335; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 37, 1082, 1088, 1093, 1098, 31, 1100, 1106, 1111, 1116, 34, 1118, 1124, 1129, 1134, or 1336-1384; and/or (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38, 1083, 1089, 1094, 32, 1101, 1107, 1112, 35, 1119, 1125, 1130 or 1385-1424; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45, 1084, 1090, 1095, 1102, 1108, 1113, 42, 1120, 1126, 1131, or 1425-1472; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46, 1085, 1096, 40, 1103, 1114, 43, 1121, 1132, 1473-1492 or 1526-1528; and/or (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47, 1091, 1097, 41, 1109, 1115, 44, 1127, 1133 or 1493-1525.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1081; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1082; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1083. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 1084; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1085; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1081; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1082; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1083; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1084; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1085; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1086; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 37; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1086; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 37; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1087; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1088; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1089. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 1090; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1085; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1091. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1087; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1088; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1089; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1090; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1085; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1091.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1092; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1093; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1094. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 1095; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1096; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1097. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1092; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1093; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1094; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1095; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1096; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1097.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 36; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1098; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 36; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1098; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 38; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 46; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 47.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1099; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1100; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1101. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 1102; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1103; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1099; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1100; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1101; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1102; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1103; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1104; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 31; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 32. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1104; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 31; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 32; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1105; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1106; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1107. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 1108; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1103; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1109. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1105; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1106; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1107; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1108; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1103; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1109.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1110; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1111; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1112. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 1113; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1114; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1115. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1110; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1111; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1112; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1113; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1114; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1115.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 30; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1116; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 32. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 30; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1116; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 32; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 45; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 40; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 41.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1117; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1118; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1119. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 1120; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1121; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1117; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1118; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1119; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1120; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1121; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1122; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 34; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 42; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 43; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1122; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 34; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 35; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 42; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 43; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1123; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1124; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1125. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 1126; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1121; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1127. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1123; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1124; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1125; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1126; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1121; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1127.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1128; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1129; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1130. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 1131; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1132; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1133. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 1128; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1129; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 1130; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 1131; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 1132; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 1133.

In one embodiment, an antibody that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence of SEQ ID NO: 33; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1134; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody further comprises a VL region comprising: (1) VL CDR1 having the amino acid sequence of SEQ ID NO: 42; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 43; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44. In one embodiment, the antibody comprises: (a) a VH region comprising: (1) VH CDR1 having the amino acid sequence of SEQ ID NO: 33; (2) VH CDR2 having the amino acid sequence of SEQ ID NO: 1134; and (3) VH CDR3 having the amino acid sequence of SEQ ID NO: 35; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence of SEQ ID NO: 42; (2) VL CDR2 having the amino acid sequence of SEQ ID NO: 43; and (3) VL CDR3 having the amino acid sequence of SEQ ID NO: 44.

In certain embodiments, a humanized anti-C10orf54 antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains one or more consensus sequences derived from related antibodies that are depicted in FIG. 17A and 17B. As used herein, the term “consensus sequence” refers to amino acid sequences containing conserved amino acids that are common to a number of sequences and variable amino acids that vary within certain amino acid sequences. Proposed consensus CDR sequences include CDRs corresponding to CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and/or CDRL3. Consensus CDR sequences of antibodies kC10ogt54 are shown in FIG. 17A and 17B. Accordingly, in some embodiments, a humanized anti-C10orf54 antibody comprises a VH region comprising: (1) a VH CDR1 having the amino acid sequence GYTFSX ₁ X ₂ WIE (SEQ ID NO: 1149), wherein X ₁ is R or T and X ₂ represents Y or H; (2) VH CDR2 having the amino acid sequence EILPGGSGSTX ₁ YNEKFKG (SEQ ID NO: 1150), where X ₁ represents N or S; and/or (3) a VH CDR3 having the amino acid sequence xxxxxxxxxX ₁ X ₂ Y (SEQ ID NO: 1151), where x is any amino acid residue, X ₁ is M or F, and X ₂ is G or D. In certain embodiments, a humanized anti-C10orf54 antibody comprises a VL region comprising: (1) a VL CDR1 having the amino acid sequence RSSQSIVHSNGNTYLE (SEQ ID NO: 45); (2) VL CDR2 having the amino acid sequence KX ₁ SNRFS (SEQ ID NO: 1152), where X ₁ represents V or L; and/or (3) VL CDR3 having the amino acid sequence FQGSHX ₁ PX ₂ T (SEQ ID NO: 1153), where X ₁ is V or F and X ₂ is W or Y. In certain embodiments, a humanized anti-C10orf54 antibody contains: (a) a VH region containing: (1) a VH CDR1 having the amino acid sequence GYTFSX ₁ X ₂ WIE (SEQ ID NO: 1149), where X ₁ is R or T and X ₂ is Y or H ; (2) VH CDR2 having the amino acid sequence EILPGGSGSTX ₁ YNEKFKG (SEQ ID NO: 1150), where X ₁ represents N or S; and/or (3) VH CDR3 having the amino acid sequence xxxxxxxxxX ¹ X ₂ Y (SEQ ID NO: 1151), where x is any amino acid residue, X ₁ is M or F, and X ₂ is G or D; and (b) a VL region comprising: (1) a VL CDR1 having the amino acid sequence RSSQSIVHSNGNTYLE (SEQ ID NO: 45); (2) VL CDR2 having the amino acid sequence KX ₁ SNRFS (SEQ ID NO: 1152), where X ₁ represents V or L; and/or (3) VL CDR3 having the amino acid sequence FQGSHX ₁ PX ₂ T (SEQ ID NO: 1153), where X ₁ is V or F and X ₂ is W or Y.

In some embodiments, the antibodies provided herein comprise a VH region that contains or includes a VH domain. In other embodiments, the antibodies provided herein comprise a VH region that contains or comprises a VH chain. In some embodiments, the antibodies provided herein comprise a VL region that contains or includes a VL domain. In other embodiments, the antibodies provided herein comprise a VL region that contains or is comprised of a VL chain. In some embodiments, the antibodies provided herein have a combination of (1) a VH domain or VH chain; and/or (2) a VL domain or VL chain.

In some embodiments, the antibody provided herein contains six or consists of six CDRs, for example, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3, which are identified in Tables 5-33. In certain embodiments, an antibody provided herein may contain less than six CDRs. In some embodiments, the antibody contains one, two, three, four, or five, or consists of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and /or VL CDR3. In specific embodiments, the antibody contains one, two, three, four, or five, or consists of one, two, three, four, or five CDRs selected from the group consisting of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and /or VL CDR3 mouse monoclonal antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, A, 353A or 305A , described in this application, or a humanized version thereof, which are identified in Tables 5-33. Accordingly, in some embodiments, the antibody contains one, two, three, four, or five, or consists of one, two, three, four, or five CDRs selected from any of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and /or VL CDR3 identified in Tables 5-33.

In some embodiments, the antibodies provided herein contain one or more (eg, one, two, or three) VH CDRs listed in Tables 5-33. In other embodiments, the antibodies provided herein contain one or more (eg, one, two, or three) VL CDRs listed in Tables 5-33. In further embodiments, the antibodies provided herein comprise one or more (eg, one, two, or three) VH CDRs listed in Tables 5-33 and one or more CDRs listed in Tables 5-33. Accordingly, in certain embodiments, the antibodies comprise a VH CDR1 having an amino acid sequence selected from any of SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, 1291-1335 and 1717-1720. In another embodiment, the antibodies comprise a VH CDR2 having an amino acid sequence selected from any of SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1336, -1384, 1556- 1559, 1829-1847 and 1917. In another embodiment, the antibodies comprise a VH CDR3 having an amino acid sequence selected from any of SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 and 1385-1424. In certain embodiments, the antibodies comprise VH CDR1 and/or VH CDR2 and/or VH CDR3 independently selected from VH CDR1, VH CDR2, VH CDR3, as shown for any of the VH regions shown in Tables 5-33. In certain embodiments, the antibodies comprise a VL CDR1 having an amino acid sequence selected from any of SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 and 1915. In another embodiment, the antibodies comprise a VL CDR2 having an amino acid sequence selected from any of SEQ ID NOs: 46, 272-275, 40, 843-846, 43, 1045- 1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1688 and 1898-1900. In another embodiment, the antibodies comprise a VL CDR3 having an amino acid sequence selected from any of SEQ ID NOs: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 and 1493-1525. In certain embodiments, the antibodies comprise VL CDR1 and/or VL CDR2 and/or VL CDR3 independently selected from VL CDR1, VL CDR2, VL CDR3, as shown for any of the VL regions shown in Tables 5-33.

In addition, this application provides antibodies containing one or more VH CDRs and one or more (eg, one, two or three) VL CDRs listed in Tables 5-33. In particular, this application provides an antibody containing VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128 , 1291-1335, 1291-1335 or 1717-1720) and VL CDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1425, -1472 , 1681-1684, 1744-1822, 1878-1896 or 1915); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720) and VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630 -1633, 1685-1688 or 1898-1900); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917) and VL CDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915 ); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917) and VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, or 1898 -1900); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424) and VL CDR1 (SEQ ID NO: 45 , 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915); VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424) and VL CDR2 (SEQ ID NO: 46 , 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1688 or 189 8-1900); VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424) and VL CDR3 (SEQ ID NO: 47 , 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917) and VL CDR1 (SEQ ID NO: 45, 253-271,42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 6 or 1915 ); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917) and VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1 685 -1688 or 1898-1900); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424) and VL CDR1 (SEQ ID NO: 45, 253-271 ,42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915, VH CDR2 (SEQ ID NO: 37 , 101 -104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886-894, 1070-1078, 1082, 1088 , 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1917), VH CDR3 (SEQ ID NO: 38, 32, 31 9, 35 , 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424) and VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045 -1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1688 or 1898-1900); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424) and VL CDR3 (SEQ ID NO: 47, 41, 44 , 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VL CDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1 878 -1896 or 1915) and VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528 , 1630-1633, 1685-1688 or 1898-1900); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VLCDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 18 78- 1896 or 1915) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630 -1633, 1685-1688 or 1898-1900) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917), VL CDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915 ) and VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1 688 or 1898-1900); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917), VL CDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915 ) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917), VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, or 1898 -1900) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR1 (SEQ ID NO: 45 , 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915) and VL C DR2 (SEQ ID NO : 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1688 or 1898-1900 ); VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR1 (SEQ ID NO: 45 , 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915) and VL C DR3 (SEQ ID NO : 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR2 (SEQ ID NO: 46 , 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1688 or 189 8-1900) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424) and VL CDR1 (SEQ ID NO: 45 , 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424) and VL CDR2 (SEQ ID NO: 46 , 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1688 or 189 8-1900); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424) and VL CDR3 (SEQ ID NO: 47 , 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917), VL CDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 96 or 1915 ) and VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633 , 1685-1688 or 1898-1900); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917), VL CDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 96 or 1915 ) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917), VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1 685 -1688 or 1898-1900) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915 ) and VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1 688 or 1898-1900); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915 ) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, or 1898 -1900) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR1 (SEQ ID NO: 45, 253-271 , 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915) and VL CDR2 (SEQ ID NO: 46, 272 -275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1688 or 1898-1900 ); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR1 (SEQ ID NO: 45, 253-271 , 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915) and VL CDR3 (SEQ ID NO: 47, 41 , 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR2 (SEQ ID NO: 46, 272-275 , 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1688 or 1898-1900) and V L CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR1 (SEQ ID NO: 45 , 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915) and VL C DR2 (SEQ ID NO : 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1688 or 1898-1900 ); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR1 (SEQ ID NO: 45 , 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915) and VL C DR3 (SEQ ID NO : 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR2 (SEQ ID NO: 46 , 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1688 or 189 8-1900) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858 , 49, 886-894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 18 29-1847 or 1917), VL CDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 96 or 1915 ), VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633 , 1685-1688 or 1898-1900) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR1 (SEQ ID NO: 36, 30, 59-62, 33, 1081, 1086, 1087, 1092, 1099, 1104, 1105, 1110, 1117, 1122, 1123, 1128, 1291-1335, or 1717 -1720), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR1 (SEQ ID NO: 45, 253-271, 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915 ), VL CDR2 (SEQ ID NO: 46, 272-275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1 688 or 1898-1900) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); VH CDR2 (SEQ ID NO: 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886 -894, 1070-1078, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1336-1384, 1556-1559, 1829-1847 or 1 917), VH CDR3 (SEQ ID NO: 38, 32, 319, 35, 883-885, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125, 1130 or 1385-1424), VL CDR1 (SEQ ID NO: 45, 253-271 , 42, 1084, 1090, 1095, 1102, 1108, 1113, 1120, 1126, 1131, 1425-1472, 1681-1684, 1744-1822, 1878-1896 or 1915), VL CDR2 (SEQ ID NO: 4 6, 272 -275, 40, 843-846, 43, 1045-1048, 1085, 1096, 1103, 1114, 1121, 1132, 1473-1492, 1526-1528, 1630-1633, 1685-1688 or 1898-1900 ) and VL CDR3 (SEQ ID NO: 47, 41, 44, 1056-1058, 1091, 1097, 1109, 1115, 1127, 1133 or 1493-1525); or any combination thereof selected from VH CDR (SEQ ID NO: 36, 30, 59-62, 33, 37, 101-104, 50, 114, 99, 100, 31, 65-74, 83-90, 95, 321, 322, 835-842, 34, 847-858, 49, 886-894 1070-1078, 38, 32, 319, 35, 883-885, 1081, 1086, 1087, 1092, 1099, 1104, 1110 , 1117, 1122, 1123, 1128, 1082, 1088, 1093, 1098, 1100, 1106, 1111, 1116, 1118, 1124, 1129, 1134, 1083, 1089, 1094, 1101, 1107, 1112, 1119, 1125 and 1130 ) and VL CDR (SEQ ID NO: 45, 253-271, 42, 46, 272-275, 40, 843-846, 43, 1045-1048, 47, 41, 44, 1056-1058, 1084, 1090, 1095 , 1102, 1108, 1113, 1120, 1126, 1131, 1085, 1096, 1103, 1114, 1121, 1132, 1091, 1097, 1109, 1115, 1127 and 1133), listed in Tables 5-33.

In certain embodiments, humanized antibodies to C10orF54 are associated with polypeptide, a fragment of polypeptide or an epitope C10orf54 with an affinity comparable to the affinity of one or more mouse monocoponal antibodies, designated as 5V, 46A, 97A, 128A, 146s, 208a, 215a, 26a, 164a, 23 0a , 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A. In addition, these humanized anti-C10orf54 antibodies may contain one, two, three or four human or humanized framework regions in the immunoglobulin heavy chain variable region and/or one, two, three or four human or humanized framework regions in the immunoglobulin light chain variable region. Also provided are FR regions of the heavy and/or light chain that contain one or more back mutations in which the FR residue of the human immunoglobulin is replaced by the corresponding residue present in the parent mouse heavy or light chain, or by another comparable residue. In some aspects, the amino acid sequences for the heavy and light chain CDR1, CDR2, and CDR3 for certain humanized anti-C10orf54 antibodies may also include one or more mutations in which a residue is introduced into the CDR, as identified in Tables 5-33. Amino acid sequences for the FR1, FR2, FR3 and FR4 heavy and light chains that can be used for humanized anti-C10orf54 antibodies are identified in Tables 5-11 and shown in FIG. 3-9, 17 and 22-25.

In certain embodiments, a humanized antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH region that contains: (1) VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 and 1828; (2) VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 52, 106, 56, 122-124, 63, 64 and 323-326; (3) VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 and 1848-1875; and/or (4) VH FR4 having the amino acid sequence of SEQ ID NO: 54, 320, 168054, 320, 1680. Accordingly, in some embodiments, the humanized antibody contains a VH region that includes VH FR1 having an amino acid sequence selected from group consisting of SEQ ID NOs: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 and 1828. In some embodiments, the humanized antibody contains VH- a region that includes VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 52, 106, 56, 122-124, 63, 64 and 323-326. In some embodiments, the humanized antibody comprises a VH region that includes VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327 -833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 and 1848-1875. In some embodiments, the humanized antibody contains a VH region that includes VH FR4 having the amino acid sequence of SEQ ID NO: 54, 320, 1680.

In certain embodiments, a humanized antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VL region that contains: (1) a VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 and 1878; (2) VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 and 1823-1826; (3) VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 and 1901; and/or (4) VL FR4 having the amino acid sequence of SEQ ID NO: 78. Accordingly, in some aspects, the humanized antibody comprises a VL region that includes VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NO : 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877, and 1878. In some aspects, the humanized antibody comprises a VL region that includes a VL FR2 having the amino acid sequence , selected from the group consisting of SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 and 1823-1826. In some aspects, the humanized antibody comprises a VL region that includes a VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 and 1901. In some aspects, the humanized antibody comprises a VL region that includes a VL FR4 having the amino acid sequence of SEQ ID NO: 78.

In certain embodiments, a humanized antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) comprises a VH region and a VL region, wherein the VH region further comprises: (1) a VH FR1 having an amino acid a sequence selected from the group consisting of SEQ ID NOs: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 and 1828; (2) VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 52, 106, 56, 122-124, 63, 64 and 323-326; (3) VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 and 1848-1875; and/or (4) VH FR4 having the amino acid sequence of SEQ ID NO: 54, 320, 168054, 320, 1680; and wherein the VL region further comprises: (1) VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615 -1629, 1743, 1877 and 1878; (2) VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 and 1823-1826; (3) VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 and 1901; and/or (4) VL FR4 having the amino acid sequence of SEQ ID NO: 78.

In addition, this application provides antibodies containing one or more (eg, one, two, three or four) VH FRs and one or more VL FRs shown in Tables 5-11. In particular, this application provides an antibody containing VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828 ) and VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828) and VL FR2 (SEQ ID NO: 76 , 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828) and VL FR3 (SEQ ID NO: 77 , 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828) and VL FR4 (SEQ ID NO: 78 ); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326) and VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823 -1826); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068 , 1069, 1689-1714 or 1901; VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326) and VL FR4 (SEQ ID NO: 78); NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848- 1875) and VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828); NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848- 1875) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326) and VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743 , 1877 or 1878); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901 ); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875) and VL FR1 (SEQ ID NO: 75, 252, 79, 277-283 , 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291 , 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VL FR1 (SEQ ID NO: 75 , 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062 -1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VL FR1 (SEQ ID NO: 75 , 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049 -1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VL FR1 (SEQ ID NO: 75 , 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VL FR2 (SEQ ID NO: 76 , 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VL FR2 (SEQ ID NO: 76 , 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823 -1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823 -1826) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285 -291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR4 (SEQ ID NO: 54, 320, 168054, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743 , 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878 ) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878 ) and VL FR4 (SEQ ID NO: 78); VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77 , 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78 ); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875) and VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823 -1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068 , 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91 , 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044 , 1062-1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93 , 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878 ); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743 , 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743 , 1877 or 1878) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743 , 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284 , 92, 1038-1044, 1062-1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR3 (SEQ ID NO: 77, 276, 81 , 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR4 (SEQ ID NO: 54 , 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO : 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR4 (SEQ ID NO: 54 , 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR3 (SEQ ID NO : 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR4 (SEQ ID NO: 54 , 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO : 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283 , 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283 , 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL Fr3 (Seq ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689, 1689 -1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283 , 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055 , 1068, 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615 -1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615 -1629, 1743, 1877 or 1878) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615 -1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055 , 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR4 (SEQ ID NO: 54 , 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291 , 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR4 (SEQ ID NO: 54 , 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038 -1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038 -1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80 , 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901 ); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80 , 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901 ) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR4 (SEQ ID NO: 54 , 320, 1680), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291 , 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR3 (SEQ ID NO: 77, 276 , 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689 -1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VL FR1 (SEQ ID NO: 75 , 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062 -1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VL FR1 (SEQ ID NO: 75 , 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062 -1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VL FR1 (SEQ ID NO: 75 , 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049 -1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VL FR2 (SEQ ID NO: 76 , 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77 , 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78 ); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823 -1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069 , 1689-1714 or 1901); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285 -291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878 ), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049 -1055, 1068, 1069, 1689-1714 or 1901); VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878 ), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878 ), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77 , 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR2 (SEQ ID NO: 76, 80 , 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR3 (SEQ ID NO: 77, 276 , 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823 -1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823 -1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068 , 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91 , 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91 , 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 4 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91 , 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044 , 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044 , 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93 , 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92 , 1038-1044, 1062-1067 or 1823-1826); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR3 (SEQ ID NO: 77, 276, 81, 285 -291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068 , 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743 , 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291 , 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743 , 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743 , 1877 or 1878), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284 , 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284 , 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR3 (SEQ ID NO: 77, 276, 81 , 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055 , 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR4 (SEQ ID NO: 54 , 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO : 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689 -1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR4 (SEQ ID NO: 54 , 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO : 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR4 (SEQ ID NO: 54 , 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR3 (SEQ ID NO : 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR4 (SEQ ID NO: 54 , 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291 , 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283 , 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283 , 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283 , 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689 -1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038 -1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055 , 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80 , 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901 ) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615 -1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81 , 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615 -1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615 -1629, 1743, 1877 or 1878), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO : 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VL FR1 (SEQ ID NO: 75 , 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062 -1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78 ); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77 , 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069 , 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878 ), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049 -1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055 , 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80 , 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901 ); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80 , 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR3 (SEQ ID NO: 77, 276 , 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77 , 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78 ); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823 -1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77 , 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91 , 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91 , 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR3 (Seq ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044 , 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO : 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878 ), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049 -1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878 ), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878 ), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77 , 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92 , 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92 , 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR3 (SEQ ID NO: 77, 276, 81, 285 -291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068 , 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743 , 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291 , 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR3 (SEQ ID NO: 53 , 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284 , 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR4 (SEQ ID NO: 54 , 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO : 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689 -1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283 , 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721 -1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615 -1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81 , 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252 , 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR2 (SEQ ID NO: 76, 80 , 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901 ) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53 , 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059 -1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77 , 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR1 (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 1550-1555, 1649-1652, 1715, 1716, 1827 or 1828), VH FR2 (SEQ ID NO: 52 , 106, 56, 122-124, 63, 64 or 323-326), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91 , 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92, 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); VH FR2 (SEQ ID NO: 52, 106, 56, 122-124, 63, 64 or 323-326), VH FR3 (SEQ ID NO: 53, 107-113, 57, 125-251, 96-98, 292 -318, 327-833, 53, 859-882, 903-1030, 1560-1614, 1653-1679, 1721-1742 or 1848-1875), VH FR4 (SEQ ID NO: 54, 320, 1680), VL FR1 (SEQ ID NO: 75, 252, 79, 277-283, 91, 1031-1037, 1059-1061, 1615-1629, 1743, 1877 or 1878), VL FR2 (SEQ ID NO: 76, 80, 284, 92 , 1038-1044, 1062-1067 or 1823-1826), VL FR3 (SEQ ID NO: 77, 276, 81, 285-291, 93, 1049-1055, 1068, 1069, 1689-1714 or 1901) and VL FR4 (SEQ ID NO: 78); or any combination thereof of VH FR (SEQ ID NO: 51, 105, 55, 115-121, 39, 58, 895-902, 52, 106, 56, 122-124, 63, 64, 323-326, 53, 107-113, 57, 125-251, 96-98, 292-318, 327-833, 53, 859-882 903-1030, 54, 320, 1680) and VL FR (SEQ ID NO: 75, 252, 79 , 277-283, 91, 1031-1037, 1059-1061, 76, 80, 284, 92, 1038-1044, 1062-1067, 77, 276, 81, 285-291, 93, 1049-1055, 1068, 9 or 78) shown in Tables 5-11.

In certain embodiments, a humanized antibody that binds to the Group A C10orf54 proteins or chimeric proteins described herein comprises a VH region comprising: (1) VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 51 , 1550-1555, 105 and 1649-1652; (2) VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 52 and 106; (3) VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1560-1614 and 1653-1679; and/or (4) VH FR4 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 54 and 1680. In certain embodiments, a humanized antibody that binds to the group A proteins or chimeric C10orf54 proteins described herein contains a VL region comprising: (1) VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1615-1629, 79 and 278; (2) VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 92, 80 and 284; (3) VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1634-1648, 81, 1689-1714, 285, 286 and 288; and/or (4) VL FR4 having the amino acid sequence of SEQ ID NO: 78. In certain embodiments, a humanized antibody that binds to the group A proteins or C10orf54 chimeric proteins described herein contains a VH region and a VL region, wherein the VH region further comprises: (1) VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 51, 1550-1555, 105 and 1649-1652; (2) VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 52 and 106; (3) VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1560-1614 and 1653-1679; and/or (4) VH FR4 having an amino acid sequence selected from the group consisting of SEQ ID NO: 54 and 1680; and wherein the VL region further comprises: (1) VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1615-1629, 79 and 278; (2) VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 92, 80 and 284; (3) VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1634-1648, 81, 1689-1714, 285, 286 and 288; and/or (4) VL FR4 having the amino acid sequence of SEQ ID NO: 78.

In certain embodiments, a humanized antibody that binds to the Group A C10orf54 proteins or chimeric proteins described herein comprises a VH region comprising: (1) VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 51 , 39, 1715, 1716, 1550, 1827, 1828, 105, 55 and 115-121; (2) VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 52, 106, 63, 64, 56, 323-326 and 122-124; (3) VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 1560, 1561, 1721-1742, 1566, 1567, 1571, 1575, 1585, 1562, 1563, 1848-1875, 1565-1568, 1570-1572, 1574, 1575, 1577, 1578, 1581, 1582, 1584, 1585, 1587, 1591, 1593, 1594, 1597, 1602, 1603, 53, 107, 96-98, 18, 57 and 327- 833; and/or (4) VH FR4 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 54 and 320. In certain embodiments, a humanized antibody that binds to group A of the C10orf54 proteins or chimeric proteins described herein comprises a VL region comprising: (1) VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1743, 75, 252, 1878, 1877, 79 and 277-283; (2) VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1823-1826, 76, 80 and 284; (3) VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 77, 276, 1901, 81 and 285-291; and/or (4) VL FR4 having the amino acid sequence of SEQ ID NO: 78. In certain embodiments, a humanized antibody that binds to the group A proteins or C10orf54 chimeric proteins described herein contains a VH region and a VL region, wherein the VH region further comprises: (1) VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 51, 39, 1715, 1716, 1550, 1827, 1828, 105, 55 and 115-121; (2) VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 52, 106, 63, 64, 56, 323-326 and 122-124; (3) VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 1560, 1561, 1721-1742, 1566, 1567, 1571, 1575, 1585, 1562, 1563, 1848-1875, 1565-1568, 1570-1572, 1574, 1575, 1577, 1578, 1581, 1582, 1584, 1585, 1587, 1591, 1593, 1594, 1597, 1602, 1603, 53, 107, 96-98, 18, 57 and 327- 833; and/or (4) VH FR4 having an amino acid sequence selected from the group consisting of SEQ ID NO: 54 and 320; and wherein the VL region further comprises: (1) VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1743, 75, 252, 1878, 1877, 79 and 277-283; (2) VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 1823-1826, 76, 80 and 284; (3) VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 77, 276, 1901, 81 and 285-291; and/or (4) VL FR4 having the amino acid sequence of SEQ ID NO: 78.

In certain embodiments, a humanized antibody that binds to the Group A C10orf54 proteins or chimeric proteins described herein comprises a VH region comprising: (1) VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 51 , 39, 105, 58, 55, 115-121 and 895-902; (2) VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 52, 106, 56 and 122-124; (3) VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 53, 107-113, 859-882, 57, 125-251 and 903-1030; and/or (4) VH FR4 having the amino acid sequence of SEQ ID NO: 54. In certain embodiments, a humanized antibody that binds to the group A proteins or C10orf54 chimeric proteins described herein comprises a VL region comprising: (1 ) VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NO: 91, 1031-1037, 79 and 1059-1061; (2) VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 92, 1038-1044, 80, 284 and 1062-1067; (3) VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 93, 1049-1055, 81, 1068, 285 and 1069; and/or (4) VL FR4 having the amino acid sequence of SEQ ID NO: 78. In certain embodiments, a humanized antibody that binds to the group A proteins or C10orf54 chimeric proteins described herein contains a VH region and a VL region, wherein the VH region further comprises: (1) VH FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 51, 39, 105, 58, 55, 115-121 and 895-902; (2) VH FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 52, 106, 56 and 122-124; (3) VH FR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 53, 107-113, 859-882, 57, 125-251 and 903-1030; and/or (4) VH FR4 having the amino acid sequence of SEQ ID NO: 54; and wherein the VL region further comprises: (1) VL FR1 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 91, 1031-1037, 79 and 1059-1061; (2) VL FR2 having an amino acid sequence selected from the group consisting of SEQ ID NO: 92, 1038-1044, 80, 284 and 1062-1067; (3) VL FR3 having an amino acid sequence selected from the group consisting of SEQ ID NOs: 93, 1049-1055, 81, 1068, 285 and 1069; and/or (4) VL FR4 having the amino acid sequence of SEQ ID NO: 78.

In some embodiments, the antibodies provided herein are antibodies that bind to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) and include antibodies containing derivatives of VH domains, VH CDRs, VL domains, and VL CDRs , described herein, that bind to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope). In addition, this application provides antibodies containing derivatives of mouse monoclonal antibodies 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, , 141A, 51A, 353A or 305A, wherein these antibodies bind to C10orf54 (eg, C10orf54 polypeptide, C10orf54 polypeptide fragment, C10orf54 epitope). Standard methods known to those skilled in the art can be used to introduce mutations into the nucleotide sequence encoding an antibody or fragment thereof provided herein, including, for example, site-directed mutagenesis and PCR-mediated mutagenesis resulting in the introduction of amino acid substitutions. In certain embodiments, these derivatives include less than 25 amino acid substitutions, less than 20 amino acid substitutions, less than 15 amino acid substitutions, less than 10 amino acid substitutions, less than 5 amino acid substitutions, less than 4 amino acid substitutions, less than 3 amino acid substitutions, or less than 2 amino acid substitutions compared to the parent molecule . In a specific embodiment, these derivatives contain conservative amino acid substitutions made at one or more positions for amino acid residues that are not predicted to be significant. A "conservative amino acid substitution" is a substitution in which an amino acid residue is replaced by an amino acid residue having a side chain of the same charge. Families of amino acid residues having side chains with equal charges are defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), non-polar side chains (e.g. alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g. threonine, valine, isoleucine) and aromatic side chains (e.g. tyrosine, phenylalanine , tryptophan, histidine). Alternatively, mutations can be introduced randomly throughout all or part of the coding sequence, for example, using saturation mutagenesis, and the resulting mutants can be screened for biological activity to identify mutants that retain activity. Once mutagenesis is performed, the encoded protein can be expressed and the activity of the protein can be determined.

In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains an amino acid sequence that is at least 35%, at least 40%, at least 45% , at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the amino acid sequence of mouse monoclonal antibodies 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A , 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A or an antigen-binding fragment thereof, such as a VH domain or a VL domain. In one embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains an amino acid sequence that is at least 35%, at least 40%, at least 45% , at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, is at least 85%, at least 90%, at least 95%, or at least 99% identical to the amino acid sequence presented in SEQ ID NO: 12-29. In another embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains an amino acid sequence that is at least 35%, at least 40%, at least 45%, by at least 50%, by at least 55%, by at least 60%, by at least 65%, by at least 70%, by at least 75%, by at least 80%, by is at least 85%, at least 90%, at least 95%, or at least 99% identical to the amino acid sequence presented in Tables 5-33. In yet another embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH CDR and/or VL CDR amino acid sequence that is at least 35%, at least 40% , at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to the amino acid sequence of the VH CDR presented in Tables 5-33, and/or amino acid sequence of the VL CDR presented in Tables 5-33.

In certain embodiments, antibodies used in accordance with the methods proposed herein have high affinity for a C10orf54 polypeptide or polypeptide fragment or an epitope thereof. In one embodiment, the antibodies used in accordance with the methods proposed herein have a higher affinity for the C10orf54 antigen than known antibodies (eg, commercially available monoclonal antibodies discussed elsewhere in this description). In a specific embodiment, antibodies used in accordance with the methods proposed herein have 2-10-fold (or greater) higher affinity for the C10orf54 antigen than a known anti-C10orf54 antibody, as assessed using the methods set forth herein. described or known to one skilled in the art (eg, in analysis using BIAcore). In accordance with these embodiments, the affinity of the antibodies, in one embodiment, is assessed in an assay using BIAcore.

In a specific embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH domain amino acid sequence and/or a VL domain amino acid sequence encoded by a nucleotide sequence that hybridizes to (1) a complementary nucleotide sequence encoding any of the VH and/or VL domains presented in Tables 2 and 4-10, under stringent conditions (for example, under conditions of hybridization with DNA on filters in 6x sodium chloride/sodium citrate (SSC) solution at approximately 45°C followed by one or more washes in 0.2xSSC/0.1% SDS at about 50-65°C), under particularly stringent conditions (e.g., nucleic acid filter hybridization conditions in 6xSSC at about 45°C followed by one or more washes in 0.1xSSC/0.2% SDS at about 68°C) or other stringent hybridization conditions known to those skilled in the art (see, for example, Ausubel, F.M. et al., eds., 1989, Current Protocols in Molecular Biology, Vol. 1, Green Publishing Associates, Inc. and John Wiley & Sons, Inc., New York on pages 6.3.1-6.3.6 and 2.10.3).

In another embodiment, an antibody that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope) contains a VH CDR amino acid sequence or a VL CDR amino acid sequence encoded by a nucleotide sequence that hybridizes to a complementary nucleotide sequence encoding either of the VH CDR and/or VL CDR presented in Tables 2 and 4-10, under stringent conditions (for example, hybridization with DNA on filters in 6xSSC at approximately 45°C followed by one or more washes in 0.2xSSC/0.1 % SDS at about 50-65°C), under particularly stringent conditions (for example, nucleic acid hybridization conditions on filters in 6xSSC at about 45°C, followed by one or more washes in 0.1xSSC/0.2% SDS at about 68°C) or other stringent hybridization conditions known to those skilled in the art (see, for example, Ausubel, F.M. et al., eds., 1989, Current Protocols in Molecular Biology, Vol. 1, Green Publishing Associates, Inc. and John Wiley & Sons, Inc., New York on pages 6.3.1-6.3.6 and 2.10.3).

In some embodiments, the antibodies provided herein are chemically modified, for example, by covalently attaching any type of molecule to the antibody. For example, but not by way of limitation, antibody derivatives include antibodies that have been chemically modified, e.g., by glycosylation, acetylation, PEGylation, phosphorylation, amidation, derivatization using known protecting/blocking groups, proteolytic cleavage, binding to a cellular ligand, or another protein, etc. Any of numerous chemical modifications can be accomplished by known methods, including, but not limited to, specific chemical cleavage, acetylation, processing regimen, use of metabolic synthesis of tunicamycin, etc. In addition, the antibody may contain one or more non-classical amino acids.

This application further provides antibodies that bind to C10orf54 (e.g., C10orf54 polypeptide, C10orf54 polypeptide fragment, C10orf54 epitope) containing a framework region known to those skilled in the art (e.g., human or non-human immunoglobulin fragment) . The framework region may be, for example, a natural or consensus framework region. In specific embodiments, the framework region of the antibody provided herein is derived from human immunoglobulin (for a list of human immunoglobulin framework regions, see, for example, Chothia et al., 1998, J, Mol. Biol., 278: 457- 479, incorporated herein by reference in its entirety). Also see Kabat et al. (1991) Sequences of Proteins of Immunological Interest (U.S. Department of Health and Human Services, Washington, D.C.), 5th edition.

In addition, this application provides antibodies that bind to C10orf54 (e.g., C10orf54 polypeptide, C10orf54 polypeptide fragment, C10orf54 epitope), antibodies containing the amino acid sequence of one or more murine monoclonal antibody CDRs 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A or 305A, including those also given in tables 5-33, or their humanized options (their humanized options ( for example, VH CDR or VL CDR from Tables 5-11), and framework regions of human immunoglobulins with one or more amino acid substitutions at one, two, three or more of the following residues: (a) rare framework residues that differ in the mouse framework an antibody (eg, a donor antibody backbone) and a human antibody backbone (eg, an acceptor antibody backbone); (b) Vernier zone residues when they differ in the donor antibody backbone and the acceptor antibody backbone; (c) residues providing interchain packing at the VH/VL interface, which differ in the donor antibody framework and the acceptor antibody framework; (d) canonical residues that differ in the sequences of the donor antibody framework and the acceptor antibody framework, in particular, in the sequences of the framework regions most important for determining the canonical class of CDR loops of a mouse antibody; (e) residues that border the CDR; (g) residues capable of interacting with the antigen; (h) residues capable of interacting with the CDR; and (i) residues in the contact zone of the VH domain and the VL domain. In certain embodiments, antibodies that bind to the C10orf54 antigen containing human immunoglobulin framework regions with one or more amino acid substitutions at one, two, three, or more of the residues identified above are C10orf54 antagonist antibodies. In certain embodiments, antibodies that bind to the C10orf54 antigen containing human immunoglobulin framework regions with one or more amino acid substitutions at one, two, three, or more of the residues identified above are C10orf54 agonistic antibodies.

Antibodies provided herein include, but are not limited to, synthetic antibodies, monoclonal antibodies, recombinantly produced antibodies, multispecific antibodies (including bispecific antibodies), human antibodies, humanized antibodies, camel antibodies, chimeric antibodies, intraantibodies, anti-idiotypic (anti- Id) antibodies and functional fragments of any of the above antibodies. Non-limiting examples of functional fragments include single chain Fv (scFv) (including, for example, monospecific, bispecific, etc.), Fab fragments, F(ab') fragments, F(ab) ₂ fragments, F(ab') ₂ Fv disulfide bonded fragments (sdFv), Fd fragments, Fv fragments, diabody, tribody, tetrabody and minibody.

In particular, the antibodies provided herein include immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, for example, molecules that contain an antigen binding site that binds to C10orf54 (e.g., a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope). The immunoglobulin molecules provided herein can be immunoglobulin molecules of any type (eg, IgG, IgE, IgM, IgD, IgA and IgY), class (eg, IgG1, IgG2, IgG3, IgG4, IgA1 and IgA2) or subclass.

Antibody variants and derivatives include functional antibody fragments that retain the ability to bind to C10orf54 (eg, C10orf54 polypeptide, C10orf54 polypeptide fragment, C10orf54 epitope). Exemplary functional fragments include Fab fragments (an antibody fragment that contains an antigen binding domain and contains a light chain and a portion of a heavy chain bridged by a disulfide bond); Fab' (an antibody fragment containing one antigen-binding domain, which is a Fab, and an additional heavy chain portion connected through a hinge region); F(ab') ₂ (two Fab' molecules connected by interchain disulfide bonds at the hinge regions of the heavy chains; Fab' molecules can be directed to the same epitope or to different epitopes); bispecific Fab (Fab molecule having two antigen-binding domains, each of which can be directed to a different epitope); single chain Fab containing a variable region, also known as sFv (antigen binding determining variable region, consisting of one light and heavy chain of an antibody linked together by a chain of 10-25 amino acids); disulfide-linked Fv or dsFv (antigen-binding-determining variable region consisting of one light and heavy chain of an antibody linked together by a disulfide bond); camel VH (the variable antigen-binding-determining region of a single heavy chain antibody in which some of the amino acids on the surface of the VH are the same as those found in the heavy chain of natural camel antibodies); bispecific sFv (sFv or dsFv molecule having two antigen-binding domains, each of which can be directed to a different epitope); diabody (a dimerized sFv formed when the VH domain of the first sFv binds to the VL domain of the second sFv, and the VL domain of the first sFv binds to the VH domain of the second sFv; these two antigen-binding sites of the diabody can be directed to the same epitope or for different epitopes); and tribody (trimerized sFv, formed in a manner similar to diabody, but in which three antigen-binding domains are combined into a single complex; these three antigen-binding domains can be directed to the same epitope or different epitopes). Antibody derivatives also include one or more CDR sequences of the antibody's antibody combining site. CDR sequence data can be joined together using a backbone when there are two or more CDR sequences. In certain embodiments, the antibody contains a single chain Fv ("scFv"). scFv are antibody fragments containing the VH and VL domains of the antibody, with these domains present as a single polypeptide chain. Typically, the scFv polypeptide further contains a polypeptide linker between the VH and VL domains, which allows the scFv to form the desired structure for binding to the antigen. For a review on scFv, see Pluckthun, The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds. Springer-Verlag, New York, pp. 269-315 (1994).

The antibodies provided herein may be monospecific, bispecific, trispecific, or have a higher degree of specificity. Multispecific antibodies may have specificity for different epitopes of the C10orf54 polypeptide or may have specificity for both the C10orf54 polypeptide and a heterologous epitope, such as a heterologous polypeptide or solid support material. In specific embodiments, the antibodies provided herein are monospecific for a particular epitope of the C10orf54 polypeptide and do not bind to other epitopes.

In addition, this application provides fusion proteins comprising an antibody provided herein that binds the C10orf54 antigen and a heterologous polypeptide. In some embodiments, the heterologous polypeptide to which the antibody is fused is useful for targeting the antibody to cells having cell surface expressed C10orf54.

In addition, this application provides panels of antibodies that bind to the C10orf54 antigen. In specific embodiments, panels of antibodies have different association rate constants, different dissociation rate constants, different affinities for the C10orf54 antigen, and/or have different specificities for the C10orf54 antigen. In some embodiments, the panels comprise or consist of about 10, about 25, about 50, about 75, about 100, about 125, about 150, about 175, about 200, about 250, about 300, about 350, about 400, about 450 , about 500, about 550, about 600, about 650, about 700, about 750, about 800, about 850, about 900, about 950, or about 1000 or more antibodies. Antibody panels can be used, for example, in 96-well or 384-well plates, such as those used in ELISA-type assays.

ANTIBODY CONJUGATES AND FUSION PROTEINS

In some embodiments, the antibodies provided herein are conjugated or recombinantly fused to a diagnostic, detectable or therapeutic agent or any other molecule. Conjugated or recombinantly fused antibodies may be useful, for example, for monitoring or predicting the onset, development, progression and/or severity of C10ogm54-mediated disease as part of a clinical trial procedure, such as determining the effectiveness of a particular therapy.

Such diagnosis and detection can be accomplished, for example, by coupling the antibody with detectable substances including, but not limited to, various enzymes such as, but not limited to, horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase; prosthetic groups such as, but not limited to, streptavidin/biotin and avidin/biotin; fluorescent materials such as, but not limited to, umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; luminescent materials such as, but not limited to, luminol; bioluminescent materials such as, but not limited to, luciferase, luciferin and aequorin; a chemiluminescent material such as, but not limited to, an acridinium-based compound or HALOTAG; radioactive materials such as, but not limited to, iodine ( ¹³¹ I, ¹²⁵ I, ¹²³ I and ¹²¹ I), carbon ( ¹⁴ C), sulfur ( ³⁵ S), tritium ( ³ H), indium ( ¹¹⁵ In, ¹¹³ In, ¹¹² In and ¹¹¹ In), technetium ( ⁹⁹ Tc), thallium ( ²⁰¹ Ti), gallium ( ⁶⁸ Ga, ⁶⁷ Ga), palladium ( ¹⁰³ Pd), molybdenum ( ⁹⁹ Mo), xenon ( ¹³³ Xe), fluorine ( ¹⁸ F), ¹⁵³ Sm, ¹⁷⁷ Lu, ¹⁵⁹ Gd, ¹⁴⁹ Pm, ¹⁴⁰ La, ¹⁷⁵ Yb, ¹⁶⁶ Ho, ⁹⁰ Y, ⁴⁷ Sc, ¹⁸⁶ Re, ¹⁸⁸ Re, ¹⁴² Pr, ¹⁰⁵ Rh, ⁹⁷ Ru, ⁶⁸ Ge, ⁵⁷ Co, ⁶⁵ Zn, ⁸⁵ Sr, ³² P, ¹⁵³ Gd, ¹⁶⁹ Yb, ⁵¹ Cr, ⁵⁴ Mn, ⁷⁵ Se, ¹¹³ Sn and ¹¹⁷ Sn; and positron-emitting metals using various types of positron emission tomography, and non-radioactive paramagnetic metal ions.

In addition, this application provides antibodies that are conjugated or recombinantly fused to a therapeutic moiety (or one or more therapeutic moieties), as well as uses thereof. The antibody may be conjugated or recombinantly fused to a therapeutic moiety, such as a cytotoxin, eg, a cytostatic or cell-destructive agent, a therapeutic agent, or a radioactive metal ion, eg, an alpha radiation source. A cytotoxin or cytotoxic agent includes any agent that is harmful to cells. Therapeutic groups include, but are not limited to, antimetabolites (eg, methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouracil, decarbazine); alkylating agents (eg, mechlorethamine, thiotepa, chlorambucil, melphalan, carmustine (BCNU stands for bis-chloroethylnitrosourea) and lomustine (CCNU stands for 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea), cyclophosphamide, busulfan, dibromomannitol, streptozotocin , mitomycin C and cis-dichlorodiamineplatinum(II) (DDP) and cisplatin); anthracyclines (eg daunorubicin (formerly daunomycin) and doxorubicin); antibiotics (eg actinomycin D (formerly actinomycin), bleomycin, mithramycin and anthramycin (AMC)); auristatin-based molecules (eg, auristatin PHE, auristatin F, monomethyl auristatin E, bryostatin 1 and solastatin 10; see Woyke et al., Antimicrob. Agents Chemother., 46: 3802-8 (2002), Woyke et al., Antimicrob . Agents Chemother., 45: 3580-4 (2001), Mohammad et al., Anticancer Drugs, 12: 735-40 (2001), Wall et al., Biochem. Biophys. Commun. 266: 76-80 ( 1999), Mohammad et al., Int. J. Oncol., 15: 367-72 (1999), all of which are incorporated herein by reference); hormones (eg, glucocorticoids, progestins, androgens and estrogens), inhibitors of DNA repair enzymes (eg, etoposide or topotecan), kinase inhibitors (eg, compound ST1571, imatinib mesylate (Kantarjian et al., Clin. Cancer Res., 8(7) ): 2167-76 (2002)); cytotoxic agents (eg, paclitaxel, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicine, doxorubicin, daunorubicin, dihydroxyanthracinedione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucorticoids, procaine, tetracaine, lidocaine, propranolol and puromycin and their analogs or homologues and compounds disclosed in US patents No. 6245759, 6399633, 6383790, 6335156, 6271242, 6242196, 6218 410, 6218372, 6057300, 6034053, 5985877, 5958769, 5925376 5922844, 5911995, 5872223, 5863904, 5840745, 5728868, 5648239, 5587459; 77, BMS-214662 and inhibitors described, for example, in US patent Nos.: 6458935, 6451812 , 6440974, 6436960, 6432959, 6420387, 6414145, 6410541, 6410539, 6403581, 6399615, 6387905, 6372747, 6369034, 6362188 634 2765, 6342487, 6300501, 6268363, 6265422, 6248756, 6239140, 6232338, 6228865, 6228856, 6225322, 6218406 , 6211193, 6187786, 6169096, 6159984, 6143766, 6133303, 6127366, 6124465, 6124295, 6103723, 6093737, 6090948, 6080870, 607 7853, 6071935, 6066738, 6063930, 6054466, 6051582, 6051574 and 6040305); topoisomerase inhibitors (eg, camptothecin; irinotecan; SN-38; topotecan; 9-aminocamptothecin; GG-211 (GI 147211); DX-8951f; IST-622; rubitecan; pyrazoloacridine; XR-5000; sentopin; UCE6; UCE1022; TAN 1518B; KT6528; NB-506; bulgarein; DNA minor groove binding agents such as Hoescht dye 33342 and Hoechst dye 33258; nitidine; fagaronine; epiberberine; coraline; beta-lapachone; VS-4-1; bisphosphonates (e.g. alendronate, cimadronate, clodronate, tiludronate, epidronate, ibandronate, neridronate, olpandronate, risedronate, pyridronate, pamidronate, zoledronate) HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors (e.g. lovastatin, simvastatin, atorvastatin, pravastatin, fluvastatin, statin, cerivastatin, Lescol, Lipitor, rosuvastatin and atorvastatin); antisense oligonucleotides (eg, those described in US Pat. Nos. 6,277,832, 5,998,596, 5,885,834, 5,734,033, and 5,618,709); adenosine deaminase inhibitors (for example, fludarabine phosphate and 2-chlorodeoxyadenosine); ibritutomab tiuxetan (Zevalin®); tositumomab (Bexxar®)) and their pharmaceutically acceptable salts, solvates, clathrates and prodrugs.

In addition, the antibody provided herein may be conjugated or recombinantly fused to a therapeutic or drug moiety that modifies a specific biological response. Therapeutic or drug groupings should not be construed as limited to classical chemical therapeutic agents. For example, the drug moiety may be a protein, peptide, or polypeptide that has the desired biological activity. Such proteins may include, for example, a toxin such as abrin, ricin A, Pseudomonas aeruginosa exotoxin, cholera toxin or diphtheria toxin; protein such as tumor necrosis factor, γ-interferon, α-interferon, nerve growth factor, platelet-derived growth factor, tissue plasminogen activator, apoptotic agent such as TNF-γ, AIM (activation inducer molecule) I (see international publication No. WO 97/33899), AIM II (see international publication no. WO 97/34911), Fas ligand (Takahashi et al., 1994, J. Immunol., 6: 1567-1574) and VEGF (see international publication no. WO 99/23105), an antiangiogenic agent, for example angiostatin, endostatin or a component of the coagulation cascade (for example tissue factor); or a biological response modifier, such as a lymphokine (eg, interferon-gamma, interleukin-1 (“IL-1”), interleukin-2 (“IL-2”), interleukin-5 (“IL-5”), interleukin -6 ("IL-6"), interleukin-7 ("IL-7"), interleukin 9 ("IL-9"), interleukin-10 ("IL-10"), interleukin-12 ("IL-12 "), interleukin-15 ("IL-15"), interleukin-23 ("IL-23"), granulocyte-monocyte colony-stimulating factor ("GM-CSF") and granulocyte colony-stimulating factor ("G-CSF")), or a growth factor (e.g., growth hormone (“GH”)), or a coagulation-inducing agent (e.g., calcium, vitamin K, tissue factors such as, but not limited to, Hageman factor (factor XII), high molecular weight kininogen (HMWK), prekallikrein (PK), coagulation-inducing protein factors II (prothrombin), factor V, XIIa, VIII, XIIIa, XI, XIa, IX, IXa, X, phospholipid and fibrin monomer).

This application further provides antibodies that are recombinantly fused or chemically conjugated (covalently or non-covalently conjugated) to a heterologous protein or polypeptide (or fragment thereof, e.g., a polypeptide consisting of about 10, about 20, about 30, about 40 , about 50, about 60, about 70, about 80, about 90, or about 100 amino acids) to form fusion proteins, as well as their use. In particular, the present invention provides fusion proteins comprising an antigen binding fragment of an antibody as provided herein (e.g., Fab fragment, Fd fragment, Fv fragment, F(ab) ₂ fragment, VH domain, VH CDR, VL domain or VL CDR), and a heterologous protein, polypeptide or peptide. In one embodiment, the heterologous protein, polypeptide, or peptide to which the antibody is fused is useful for targeting the antibody to a specific cell type, for example, a cell that expresses C10orf54 or the C10orf54 receptor. For example, an antibody that binds to a cell surface receptor expressed by a particular cell type (eg, a cell of the immune system) can be fused or conjugated to a modified antibody provided herein.

The conjugated or fusion protein may comprise any antibody provided herein as set forth herein and a heterologous polypeptide. In one embodiment, the conjugated or fusion protein provided herein comprises the VH or VL domain of any mouse monoclonal antibody 5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A , 33A, 39A, 124A, 175A, 321D, 141A, 51A, 353A, or 305A, as listed in Table 2, and a heterologous polypeptide. In another embodiment, the conjugated or fusion protein provided herein comprises a VH domain having the amino acid sequence of any of the VH domains set forth in Tables 5-33 and/or a VL domain having the amino acid sequence of any of the VL domains, shown in Tables 5-33, and a heterologous polypeptide. In another embodiment, the conjugated or fusion protein provided herein comprises one or more VH CDRs having the amino acid sequence of any of the VH CDRs listed in Tables 5-33 and a heterologous polypeptide. In another embodiment, the conjugated or fusion protein comprises one or more VL CDRs having the amino acid sequence of any of the VL CDRs listed in Tables 5-33 and a heterologous polypeptide. In another embodiment, the conjugated or fusion protein provided herein comprises at least one VH domain and at least one VL domain listed in Tables 5-33 and a heterologous polypeptide. In yet another embodiment, the conjugated or fusion protein provided herein comprises at least one VH CDR and at least one VL CDR listed in Tables 5-33 and a heterologous polypeptide.

In addition, the antibody provided herein may be conjugated to therapeutic moieties such as a radioactive metal ion, for example, alpha radiation sources such as ²¹³ Bi, or macrocyclic chelators useful for conjugating radioactive metal ions, including but not limited to limited to this, ¹³¹ In, ¹³¹ Lu, ¹³¹ Y, ¹³¹ Ho, ¹³¹ Sm, with polypeptides. In certain embodiments, the macrocyclic chelator is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA), which can be attached to the antibody via a linker molecule. Such linker molecules are widely known in the art and are described in Denardo et al., 1998, Clin. Cancer Res., 4(10): 2483-90; Peterson et al., 1999, Bioconjug. Chem., 10(4): 553-7; and Zimmerman et al., 1999, Nucl. Med. Biol., 26(8): 943-50, each of which is incorporated by reference in its entirety.

In addition, to facilitate purification, the antibodies provided herein can be fused to marker sequences such as peptides. In specific embodiments, the marker amino acid sequence is a hexahistidine peptide, such as the tag provided in the pQE vector (QIAGEN, Inc.), which is commercially available, among many others. As described in Gentz et al., 1989, Proc. Natl. Acad. Sci. USA, 86: 821-824, for example, the presence of hexahistidine provides convenient purification of the fusion protein. Other peptide tags useful for purification include, but are not limited to, a hemagglutinin (“HA”) tag, which corresponds to an epitope of the influenza virus hemagglutinin protein (Wilson et al., 1984, Cell, 37:767), and a “FLAG” tag. .

Methods for fusing or conjugating therapeutic moieties (including polypeptides) with antibodies are well known, see, for example, Arnon et al., "Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy", in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Delivery,” in Controlled Drug Delivery (2nd Ed.), Robinson et al. (eds.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, “Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review,” in Monoclonal Antibodies 84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); "Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy", in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press, 1985), Thorpe et al., 1982, Immunol. Rev., 62: 119-58; US Patent Nos. 5336603, 5622929, 5359046, 5349053, 5447851, 5723125, 5783181, 5908626, 5844095 and 5112946; EP 307434; EP 367166; EP 394827; PCT publications WO 91/06570, WO 96/04388, WO 96/22024, WO 97/34631 and WO 99/04813; Ashkenazi et al., Proc. Natl. Acad. Sci. USA, 88: 10535-10539, 1991; Traunecker et al., Nature, 331: 84-86, 1988; Zheng et al., J. Immunol., 154: 5590-5600, 1995; Vil et al., Proc. Natl. Acad. Sci. USA, 89: 11337-11341, 1992, which are incorporated herein by reference in their entirety.

Fusion proteins can be produced, for example, using gene shuffling, motif shuffling, exon shuffling, and/or codon shuffling techniques (collectively referred to as “DNA shuffling”). DNA shuffling can be used to alter the activity of the antibodies provided herein (eg, to produce antibodies with higher affinity and lower dissociation rate constants). In general, see US Pat. Nos. 5,605,793, 5,811,238, 5,830,721, 5,834,252, and 5,837,458; Patten et al., 1997, Curr. Opinion Biotechnol., 8: 724-33; Harayama, 1998, Trends Biotechnol. 16(2): 76-82; Hansson et al., 1999, J. Mol. Biol., 287: 265-76; and Lorenzo and Blasco, 1998, Biotechniques, 24(2): 308-313 (each of these patents and each of these publications is hereby incorporated by reference in its entirety). Antibodies or encoded antibodies can be altered using random mutagenesis using error-prone PCR, random nucleotide insertion, or other methods before recombination occurs. A polynucleotide encoding an antibody provided herein may be recombined with one or more components, motifs, sections, portions, domains, fragments, etc. one or more than one of the heterologous molecules.

The antibody provided herein may also be conjugated to a second antibody to form an antibody heteroconjugate, as described in US Pat. No. 4,676,980, which is incorporated herein by reference in its entirety.

A therapeutic moiety or drug conjugated or recombinantly fused to an antibody provided herein that binds the C10orf54 antigen must be selected to achieve the desired prophylactic or therapeutic effect(s). In certain embodiments, the antibody is a modified antibody. The practitioner or other health care professional should consider the following when deciding which therapeutic moiety or drug to be conjugated or recombinantly fused to an antibody provided herein: the nature of the disease, the severity of the disease, and the condition of the subject.

Antibodies proposed in this application can also be attached to solid supports, which are particularly useful for performing immunoassays or purifying the target antigen. Such solid supports include, but are not limited to, glass, cellulose, polyacrylamide, nylon, polystyrene, polyvinyl chloride, or polypropylene.

ANTIBODY-DRUG CONJUGATE (ADC)

In some embodiments, this application provides antibody-drug conjugates, including the antibody-drug conjugate of formulas (Ia) and (Ib) below:

or a pharmaceutically acceptable salt thereof;

Where:

A is an antibody or antibody fragment;

the two cysteine residues depicted are formed by the opening of the cysteine-cysteine disulfide bond in A;

each of X and X' independently represents O, S, NH or NR ¹ where R ¹ represents C _1-6 alkyl;

W _a represents =N-, =CH-, =CHCH ₂ -, =C(R ² )- or =CHCH(R ² )-; W _b represents -NH-, -N(R ¹ )-, -CH ₂ -, -CH ₂ -NH-, -CH ₂ -N(R ¹ )-, -CH ₂ CH ₂ -, -CH(R ² )-or -CH ₂ CH(R ² )-; where R ¹ and R ² independently represent C _1-6 alkyl;

CTX is a cytotoxin;

R represents any chemical group; or R is missing;

each L ¹ , L ² and L ³ independently represents a linker selected from the group consisting of -O-, -C(O)-, -S-, -S(O)-, -S(O) ₂ -, -NH-, -NCH ₃ -, -(CH ₂ ) _q -, -NH(CH ₂ ) ₂ NH-, -OC(O)-, -CO ₂ -, -NHCH ₂ CH ₂ C(O)-, -C(O)NHCH ₂ CH ₂ NH-, -NHCH ₂ C(O)-, -NHC(O)-, -C(O)NH-, -NCH ₃ C(O)-, -C(O) NCH ₃ -, -(CH ₂ CH ₂ O) _p , -(CH ₂ CH ₂ O) _p CH ₂ CH ₂ -, -CH ₂ CH ₂ -(CH ₂ CH ₂ O) _p -, -OSH(CH ₂ O-) ₂ , -(AA) _r -, cyclopentanyl, cyclohexanyl, unsubstituted phenylenyl and phenylenyl substituted with 1 or 2 substituents selected from the group consisting of a halogen atom, CF ₃ -, CF ₃ O-, CH ₃ O-, -C(O)OH, -C(O)OC _1-3 alkyl, -C(O)CH ₃ , -CN, -NH-, -NH ₂ , -O-, -OH, -NHCH ₃ , -N (CH ₃ ) ₂ and C _1-3 alkyl;

a, b and c are each independently an integer 0, 1, 2 or 3, provided that at least one of a, b or c is 1;

k and k' are each independently an integer 0 or 1;

each p is independently an integer from 1 to 14;

each q is independently an integer from 1 to 12;

each symbol AA independently represents an amino acid;

each r represents 1-12;

m is equal to an integer from 1 to 4;

n is equal to an integer from 1 to 4; And

connection represents a single or double bond.

In certain embodiments of the antibody-drug conjugate of formula (Ib), R is selected from the group consisting of W, (L ¹ ) _a , (L ² ) _b , (L ³ ) _c , Z, W-(L ¹ ) _a -( L ² ) _b -(L ³ ) _c , (L ¹ ) _a -(L ² ) _b -(L ³ ) _c -Z and W-(L ¹ ) _a -(L ² ) _b -(L ³ ) _c -Z, which are defined in this specification. In certain embodiments, R is selected from the group consisting of W, (L ¹ ) _a , (L ² ) _b , (L ³ ) _c and W-(L ¹ ) _a -(L ² ) _b -(L ³ )c. In certain embodiments, R is selected from the group consisting of Z, (L ¹ ) _a -(L ² ) _b -(L ³ ) _c -Z and W-(L ¹ ) _a -(L ² ) _b -(L ³ ) _c -Z.

In certain embodiments of the antibody-drug conjugate of formula (Ia) or (Ib), n is the integer 2 (eg, in the case of two interchain disulfide bonds between the heavy chain and the light chain). In certain embodiments, n is equal to the integer 3 (eg, in the case of two interchain disulfide bonds between the heavy chain and the light chain and one interchain disulfide bond between the hinge regions of the heavy chains). In certain embodiments, n is equal to the integer 4 (eg, in the case of two interchain disulfide bonds between the heavy chain and the light chain and two interchain disulfide bonds between the hinge regions of the heavy chains).

In certain embodiments of the antibody-drug conjugate of formula (Ib), R is a detectable probe. In certain embodiments, R is a fluorophore, chromophore, radiolabel, enzyme, ligand, antibody, or antibody fragment. In certain embodiments, R is a ligand (eg, a ligand specific for a receptor on a tumor cell, such as prostate specific membrane antigen, or on a virus-infected cell, such as a human immunodeficiency virus (HIV)-infected cell).

In certain embodiments of the antibody-drug conjugate of formula (Ib), R is linked to the remainder of the linker molecule via an amide, N-(C _1-6 alkyl)amide, carbamate, N-(C _1-6 alkyl)carbamate, amine, N- (C _1-6 alkyl)amine, ether, thioether, urea, N-(C _1-6 alkyl)urea or N,N-di(C _1-6 alkyl)urea.

In certain embodiments of the antibody-drug conjugate of formula (Ia) or (Ib), each of L ¹ , L ² and L ³ is independently selected from the group consisting of -NHC(O)-, -C(O)NH-, -( CH ₂ CH ₂ O) _p , -(CH ₂ CH ₂ O) _p CH ₂ CH ₂ -, -CH ₂ CH ₂ -(CH ₂ CH ₂ O) _p -, -OCH(CH ₂ O-) ₂ , - (AA) _r -, unsubstituted phenylenyl and phenylenyl substituted with 1 or 2 substituents selected from the group consisting of a halogen atom, CF ₃ -, CF ₃ O-, CH ₃ O-, -C(O)OH, -C( O)OS _1-3 alkyl, -C(O)CH ₃ , -CN, -NH-, -NH ₂ , -O-, -OH, -NHCH ₃ , -N(CH ₃ ) ₂ and C _1-3 alkyl; where a, b and c are each independently 0 or 1; and each p and r are independently 1, 2, or 3. In certain embodiments, one or more of L ¹ , L ² , and L ³ is -(AA) _r -, where -(AA) _r - is ValCit (eg, the first amino acid is valine, the second amino acid is citrulline, and g is 1). In certain embodiments, one or more of L ¹ , L ² and L ³ is -(AA) _r -, where - (AA) _{r -} is ValAla (for example, the first amino acid is valine, the second amino acid is alanine , and r is equal to 1). In certain embodiments, one or more of L ¹ , L ² and L ³ is phenylenyl substituted with -C(O)OH and -NH ₂ . In certain embodiments, one or more of L ¹ , L ² and L ³ is phenylenyl substituted with -C(O)O- and -NH-. In certain embodiments, one or more of L ¹ , L ² and L ³ is phenylenyl substituted with -OC(O)- and -NH-. In certain embodiments, one or more of L ¹ , L ² and L ³ is phenylenyl substituted with -O- and -NH-. In certain embodiments, one or more of L ¹ , L ² and L ³ is para-aminobenzyl (PAB), which is optionally substituted with -C(O)O-, -OC(O)- or -O-. In certain embodiments, L ¹ is -(CH ₂ ) _q -, L ² is absent, L ³ is absent, and CTX is connected to a (L ¹ ) _a -(L ² ) _b -(L ³ ) _amide bond. In certain embodiments, L ¹ is -(CH ₂ ) _q -, L ² is -(OCH ₂ CH ₂ ) _p -, L ³ is absent, and CTX is coupled to (L ¹ ) _a -(L ² ) _b -( L ³ ) _with an amide bond. In certain embodiments, L ¹ is -(CH ₂ CH ₂ O) _p -, L ² is -(CH ₂ ) _q -, L ³ is absent, and CTX is coupled to (L ¹ ) _a - (L ² ) _b - (L ³ ) _with an amide bond. In certain embodiments, each L ¹ is independently selected from the group consisting of -(CH ₂ CH ₂ O) _p CH ₂ CH ₂ - and -CH ₂ CH ₂ -(CH ₂ CH ₂ O) _p -, L ² absent, L ³ is absent, and CTX is connected to the (L ¹ ) _a -(L ² ) _b -(L ³ ) _amide bond. In certain embodiments, each L ¹ is independently selected from the group consisting of -(CH2) _q -, -(CH ₂ CH ₂ O) _p , -(CH ₂ CH ₂ O) _p CH ₂ CH ₂ -, -CH ₂ CH ₂ -(CH ₂ CH ₂ O) _p - and -C(O)-, L ² is Val-Cit, L ³ is PAB, and CTX is connected to (L ¹ ) _a -(L ² ) _b -(L ³ ) _with an amide bond. In certain embodiments, each L ¹ is independently selected from the group consisting of -(CH ₂ ) _q -, -(CH ₂ CH ₂ O) _p , -(CH ₂ CH ₂ O) _p CH ₂ CH ₂ -, -CH ₂ CH ₂ -(CH ₂ CH ₂ O) _p - and -C(O)-, L ² is Val-Cit, L ³ is PAB, and CTX is connected to (L ¹ ) _a -(L ² ) _b -( L ³ ) _with an amide bond. In certain embodiments, each L ¹ is independently selected from the group consisting of -(CH ₂ ) _q -, -(CH ₂ CH ₂ O) _p , -(CH ₂ CH ₂ O) _p CH ₂ CH ₂ -, -CH ₂ CH ₂ -(CH ₂ CH ₂ O) _p - and -C(O)-, L ² is Val-Ala, L ³ is PAB, and CTX is connected to (L ¹ ) _a -(L ² ) _b -( L ³ ) _with an amide bond.

In certain embodiments of the antibody-drug conjugate of formula (Ia) or (Ib), CTX is selected from the group consisting of a tubulin stabilizer, a tubulin destabilizer, a DNA alkylating agent, a DNA small groove ligand, a DNA intercalator, a topoisomerase I inhibitor, a topoisomerase II inhibitor, an gyrase, protein synthesis inhibitor, proteasome inhibitor and antimetabolite.

In certain embodiments of the antibody-drug conjugate of formula (Ia) or (Ib), CTX is a chemotherapeutic agent. Those of ordinary skill in the art are aware of the appropriate chemotherapeutic agents described, for example, in Chu E., DeVite V.T., 2012, Physicians' Cancer Chemotherapy Drug Manual, 2012 (Jones & Bartlett Learning Oncology) and similar documents.

In certain embodiments, CTX may be any US Food and Drug Administration (FDA) approved chemotherapeutic agent. In certain embodiments, CTX can be any FDA-approved chemotherapeutic agent used to treat cancer.

In certain embodiments, CTX is selected from the group consisting of alkylating agents, anthracyclines, cytoskeletal damage agents (taxanes), epothilones, histone deacetylase (HDAC) inhibitor, topoisomerase I inhibitor, topoisomerase II inhibitor, kinase inhibitor, monopolytic antibodies, nucleotide analogue, peptide an antibiotic, a platinum-based agent, a retinoid, a vinca alkaloid or its derivative, and a radioactive isotope.

In certain embodiments, CTX is selected from the group consisting of actinomycin, all-trans retinoic acid, azacitidine, azathioprine, bleomycin, bortezomib, carboplatin, capecitabine, cisplatin, chlorambucil, cyclophosphamide, cytarabine, daunorubicin, docetaxel, doxifluridine, doxorubicin, epirubicin, on, etoposide, fluorouracil, gemcitabine, hydroxyurea, idarubicin, imatinib, irinotecan, mechlorethamine, mercaptopurine, methotrexate, mitoxantrone, oxaliplatin, paclitaxel, pemetrexed, teniposide, thioguanine, topotecan, valrubicin, vinblastine, vindesine, and vinorelbine.

In certain embodiments, CTX is selected from the group consisting of a tubulin stabilizer, a tubulin destabilizer, a DNA alkylating agent, a DNA small groove ligand, a DNA intercalator, a topoisomerase I inhibitor, a topoisomerase II inhibitor, a gyrase inhibitor, a protein synthesis inhibitor, a proteasome inhibitor, and an antimetabolite.

In certain embodiments, CTX is selected from the group consisting of actinomycin D, amonafide, auristatin, benzophenone, benzothiazole, calicheamicin, camptothecin, CC-1065 (NSC 298223), cemadotin, colchicine, combretastatin A4, dolastatin, doxorubicin, elinafide, emtansine (DM1) , etoposide, KF-12347 (leinamycin), maytansinoid, methotrexate, mitoxantrone, nocodazole, proteasome inhibitor 1 (PSI 1), roridin A, T-2 toxin (trichothecene analog), taxol, tubulisin, Velcade® and vincristine. In certain embodiments, CTX is auristatin, calicheamicin, maytansinoid, or tubulisin.

In certain embodiments, the cytotoxin is pyrrolobenzodiazepine (PBD), calicheamicin, doxorubicin, camptothecin, duocarmycin, DM1, DM4, maytansinoid, or tubulisin. In certain embodiments, CTX is auristatin, PDB, calicheamicin, doxorubicin, camptothecin, duocarmycin, DM1, DM4, maytansinoid, or tubulisin. In certain embodiments, the CTX is an auristatin, for example, monomethyl auristatin F (MMAF) and monomethyl auristatin E (MMAE). In certain embodiments, the cytotoxin is a PBD.

In certain embodiments, CTX is MMAE, MMAF, PDB, calicheamicin γ, mertansine, or T2 tubulisin.

In certain embodiments, CTX is MMAE or MMAF, the structures of which are given below:

In certain embodiments, the CTX is a PDB selected from the group consisting of:

And

In certain embodiments, CTX is T2 tubulisin.

In certain embodiments, CTX is T3 tubulisin or T4 tubulisin, the structures of which are given below:

In some embodiments, this application provides antibody-drug conjugates, including an antibody-drug conjugate of formula (Ic) below:

or a pharmaceutically acceptable salt thereof,

Where:

A is an anti-C10orf54 antibody, possibly a humanized anti-C10orf54 antibody;

the two cysteine residues depicted are formed by the opening of the cysteine-cysteine disulfide bond in A;

L is a cleavable or non-cleavable linker;

CTX is a cytotoxin linked to an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond;

connection represents a single or double bond; And

n is equal to an integer from 1 to 4.

In some embodiments, this application provides antibody-drug conjugates, including an antibody-drug conjugate of formula (Ic1) below:

or a pharmaceutically acceptable salt thereof,

Where:

A is an anti-C10orf54 antibody, possibly a humanized anti-C10orf54 antibody;

the two cysteine residues depicted are formed by the opening of the cysteine-cysteine disulfide bond in A;

L is a cleavable or non-cleavable linker;

CTX is a cytotoxin linked to an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond; And

n is equal to an integer from 1 to 4.

In some embodiments, this application provides antibody-drug conjugates, including an antibody-drug conjugate of formula (Ic2) below:

or a pharmaceutically acceptable salt thereof,

Where:

A is an anti-C10orf54 antibody, possibly a humanized anti-C10orf54 antibody;

the two cysteine residues depicted are formed by the opening of the cysteine-cysteine disulfide bond in A;

L is a cleavable or non-cleavable linker;

CTX is a cytotoxin linked to an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond; And

n is equal to an integer from 1 to 4.

In certain embodiments of the antibody-drug conjugate of formula (Ic), (Ic1) or (Ic2), the exposed cysteine-cysteine disulfide bond in A is an interchain disulfide bond. In certain embodiments, when the exposed cysteine-cysteine disulfide bond in A is an interchain disulfide bond, n is 4 (eg, in the case of two interchain disulfide bonds between the heavy chain and the light chain and two interchain disulfide bonds between the hinge regions of the heavy chains). In certain embodiments, when the exposed cysteine-cysteine disulfide bond in A is an interchain disulfide bond, n is 3 (eg, in the case of two interchain disulfide bonds between the heavy chain and the light chain and one interchain disulfide bond between the hinge regions of the heavy chains). In certain embodiments, when the exposed cysteine-cysteine disulfide bond in A is an interchain disulfide bond, n is 2 (eg, in the case of two interchain disulfide bonds between a heavy chain and a light chain).

In certain embodiments of the antibody-drug conjugate of formula (Ic), (Ic1) or (Ic2), CTX is auristatin, pyrrolobenzodiazepine (PDB), calicheamicin, doxorubicin, camptothecin, duocarmycin, DM1, DM4, maytansinoid or tubulisin, wherein CTX is coupled with an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond. In certain embodiments, CTX is auristatin linked to an L amide bond or carbamate bond. In certain embodiments, CTX is MMAF linked to an L amide bond. In certain embodiments, CTX is MMAE linked to an L carbamate bond. In certain embodiments, CTX is a PBD linked to an L amide bond or a carbamate bond.

In certain embodiments of the antibody-drug conjugate of formula (Ic), (Ic1) or (Ic2), L is a non-cleavable linker.

In certain embodiments of the antibody-drug conjugate of formula (Ic), (Ic1) or (Ic2), L is:

-(CH ₂ ) _m C(O)-,

-(CH ₂ CH ₂ O) _p (CH ₂ CH ₂ )C(O)- or

-(CH ₂ CH ₂ )(OSH ₂ CH ₂ ) _p C(O)-;

where m is equal to an integer from 5 to 11, and p is equal to an integer from 1 to 3.

In certain embodiments of the antibody-drug conjugate of formula (Ic), (Ic1) or (Ic2), L is a cleavable linker.

In certain embodiments of the antibody-drug conjugate of formula (Ic), (Ic1) or (Ic2), L is:

-(CH2) _m C(O)-Val-Ala-PAB-C(O)-,

-(CH2) _m C(O)-Val-Cit-PAB-C(O)-,

-(CH ₂ CH ₂ O) _p (CH ₂ CH ₂ )C(O)-Val-Ala-PAB-C(O)-,

-(CH ₂ CH ₂ O) _p (CH ₂ CH ₂ )C(O)-Val-Cit-PAB-C(O)-,

-(CH ₂ CH ₂ )(OCH ₂ CH ₂ ) _p C(O)-Val-Ala-PAB-C(O)- or

-(CH ₂ CH ₂ )(OCH ₂ CH ₂ ) _p C(O)-Val-Cit-PAB-C(O)-;

where m is equal to an integer from 5 to 11, and p is equal to an integer from 1 to 3; And

where RAV has the following structure:

In certain embodiments of the antibody-drug conjugate of formula (Ic), (Ic1) or (Ic2), CTX is auristatin. In certain embodiments, CTX is MMAF. In certain embodiments, CTX is MMAE. In certain embodiments, CTX is PDB.

In certain embodiments of the antibody-drug conjugate of formula (Ic), (Ic1) or (Ic2), n is 2, 3 or 4.

In certain embodiments of the antibody-drug conjugate of formula (Ic), (Ic1) or (Ic2), CTX is MMAF and L is -( _CH2 ) _5C (O)-. In certain embodiments, CTX is MMAE and L is -(CH ₂ ) ₅ C(O)-Val-Ala-PAB-OC(O)-. In certain embodiments, CTX is PBD and L is -(CH ₂ ) ₅ C(O)-Val-Ala-PAB-OC(O)- or -(CH ₂ ) ₅ C(O)-Val-Cit- PAB-OC(O)-.

In certain embodiments, the antibody-drug conjugate has the following formula:

In certain embodiments, the antibody-drug conjugate has the following formula:

In certain embodiments, the antibody-drug conjugate has the following formula:

In certain embodiments, the antibody-drug conjugate has the following formula:

In certain embodiments, the antibody-drug conjugate has one of the following formulas:

And

In certain embodiments, the antibody-drug conjugate has one of the following formulas:

And

In some embodiments, this application provides an antibody-drug conjugate of formula (Id) below:

Where:

L is a cleavable or non-cleavable linker;

CTX is a cytotoxin linked to an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond;

S _x represents a sulfur atom from a first cysteine residue, and S _y represents a sulfur atom from a second cysteine residue, wherein the first cysteine residue and the second cysteine residue come from different chains and/or from the same chain of a multi-chain antibody;

connection represents a single or double bond; And

n is equal to an integer from 1 to 4.

In some embodiments, this application provides an antibody-drug conjugate of formula (Id1) below:

Where:

L is a cleavable or non-cleavable linker;

CTX is a cytotoxin linked to an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond;

S _x represents a sulfur atom from a first cysteine residue, and S _y represents a sulfur atom from a second cysteine residue, wherein the first cysteine residue and the second cysteine residue come from different chains and/or from the same chain of a multi-chain antibody; And

n is equal to an integer from 1 to 4.

In some embodiments, this application provides an antibody-drug conjugate of the following formula (Id2):

Where:

L is a cleavable or non-cleavable linker;

CTX is a cytotoxin linked to an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond;

S _x represents a sulfur atom from a first cysteine residue, and S _y represents a sulfur atom from a second cysteine residue, wherein the first cysteine residue and the second cysteine residue come from different chains and/or from the same chain of a multi-chain antibody; And

n is equal to an integer from 1 to 4.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), CTX is auristatin, pyrrolobenzodiazepine (PDB), calicheamicin, doxorubicin, camptothecin, duocarmycin, DM1, DM4, maytansinoid or tubulisin, wherein CTX is coupled with an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond. In certain embodiments, CTX is auristatin linked to an L amide bond or carbamate bond. In certain embodiments, CTX is MMAF linked to an L amide bond. In certain embodiments, CTX is MMAE linked to an L carbamate bond. In certain embodiments, CTX is a PBD linked to an L amide bond or a carbamate bond.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), the multichain antibody contains two heavy chains and two light chains.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), the first cysteine residue is derived from the first heavy chain and the second cysteine residue is derived from the second heavy chain of the multichain antibody.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), the first cysteine residue is derived from the heavy chain and the second cysteine residue is derived from the light chain of the multichain antibody.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), the first and second cysteine residues are derived from the same heavy chain of a multichain antibody.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), the multichain antibody is an anti-C10orf54 antibody, possibly a humanized anti-C10orf54 antibody.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), the first cysteine residue is derived from the heavy chain and the second cysteine residue is derived from the light chain of the multichain antibody.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), the first and second cysteine residues are derived from the same heavy chain of a multichain antibody.

In certain embodiments of the antibody-drug conjugate of formula (Id), the antibody-drug conjugate has the following formula:

wherein each heavy chain of the multi-chain antibody is designated by the letter H, and each light chain of the multi-chain antibody is designated by the letter L; and communication represents a single or double bond. In certain embodiments of the antibody-drug conjugate of formula (Id), the antibody-drug conjugate has the following formula:

wherein each heavy chain of a multi-chain antibody is designated by the letter H, and each light chain of a multi-chain antibody is designated by the letter L; and communication represents a single or double bond. In certain embodiments of the antibody-drug conjugate of formula (Id1), the antibody-drug conjugate has the following formula:

where each heavy chain of a multi-chain antibody is designated by the letter H, and each light chain of a multi-chain antibody is designated by the letter L.

In certain embodiments of the antibody-drug conjugate of formula (Id1), the antibody-drug conjugate has the following formula:

where each heavy chain of a multi-chain antibody is designated by the letter H, and each light chain of a multi-chain antibody is designated by the letter L.

In certain embodiments of the antibody-drug conjugate of formula (Id2), the antibody-drug conjugate has the following formula:

where each heavy chain of a multi-chain antibody is designated by the letter H, and each light chain of a multi-chain antibody is designated by the letter L.

In certain embodiments of the antibody-drug conjugate of formula (Id2), the antibody-drug conjugate has the following formula:

where each heavy chain of a multi-chain antibody is designated by the letter H, and each light chain of a multi-chain antibody is designated by the letter L.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), the multichain antibody contains mutations in one or more cysteine residues in the hinge regions of the two heavy chains. In certain embodiments, one or more cysteine residues are replaced by mutations with structurally related amino acids. In certain embodiments, one or more cysteine residues are mutated to alanines.

In certain embodiments of the antibody-drug conjugate of formula (Id), where the multichain antibody contains mutations in one or more cysteine residues in the hinge regions of two heavy chains, the antibody-drug conjugate has the following formula:

wherein each heavy chain of the multi-chain antibody is designated by the letter H, and each light chain of the multi-chain antibody is designated by the letter L; and communication represents a single or double bond. For embodiments of the antibody-drug conjugate of formula (Id) above, the ADC has a drug to antibody ratio (DAR) of 3 (three drug molecules per antibody molecule). As set forth herein, such ADCs can be prepared as set forth herein by introducing mutations into one or more hinge region cysteine residues of human IgG1 (e.g., 1 hinge region cysteine residue), human IgG2 (e.g., 3 hinge cysteine residue), human IgG3 (eg, 10 hinge cysteine residues) or human IgG4 (eg, 1 hinge cysteine residue).

In certain embodiments of the antibody-drug conjugate of formula (Id), where the multichain antibody contains mutations in one or more cysteine residues in the hinge regions of two heavy chains, the antibody-drug conjugate has the following formula:

wherein each heavy chain of a multi-chain antibody is designated by the letter H, and each light chain of a multi-chain antibody is designated by the letter L; and communication represents a single or double bond. For embodiments of the antibody-drug conjugate of formula (Id) above, the ADC has a DAR of 2 (two drug molecules per antibody molecule). As set forth herein, such ADCs can be generated by introducing mutations into one or more of the hinge region cysteines of human IgG1 (e.g., 2 hinge cysteines), human IgG2 (e.g., 4 hinge cysteines), human IgG3 (eg, 11 hinge cysteine residues) or human IgG4 (eg, 2 hinge cysteine residues). In certain embodiments of the antibody-drug conjugate of formula (Id) L is a non-cleavable linker.

In certain embodiments of the antibody-drug conjugate of formula (Id1), where the multichain antibody contains mutations in one or more cysteine residues in the hinge regions of two heavy chains, the antibody-drug conjugate has the following formula:

wherein each multi-chain antibody heavy chain is designated by the letter H and each multi-chain antibody light chain is designated by the letter L. For the antibody-drug conjugate embodiments of formula (Id1) given above, the ADC has a DAR of 3 (three drug molecules per antibody molecule ). As set forth herein, such ADCs can be generated by introducing mutations into one or more hinge region cysteines of human IgG1 (eg, 1 hinge cysteine), human IgG2 (eg, 3 hinge cysteines), human IgG3 (eg, 10 hinge cysteine residues) or human IgG4 (eg, 1 hinge cysteine residue).

In certain embodiments of the antibody-drug conjugate of formula (Id1), where the multichain antibody contains mutations in one or more cysteine residues in the hinge regions of two heavy chains, the antibody-drug conjugate has the following formula:

wherein each multi-chain antibody heavy chain is designated by the letter H and each multi-chain antibody light chain is designated by the letter L. For the antibody-drug conjugate embodiments of formula (Id1) given above, the ADC has a DAR of 2 (two drug molecules per antibody molecule ). As set forth herein, such ADCs can be generated by introducing mutations into one or more of the hinge region cysteines of human IgG1 (e.g., 2 hinge cysteines), human IgG2 (e.g., 4 hinge cysteines), human IgG3 (eg, 11 hinge cysteine residues) or human IgG4 (eg, 2 hinge cysteine residues). In certain embodiments of the antibody-drug conjugate of formula (Id1), L is a non-cleavable linker.

In certain embodiments of the antibody-drug conjugate of formula (Id2), where the multichain antibody contains mutations in one or more cysteine residues in the hinge regions of two heavy chains, the antibody-drug conjugate has the following formula:

wherein each multi-chain antibody heavy chain is designated by the letter H and each multi-chain antibody light chain is designated by the letter L. For the antibody-drug conjugate embodiments of formula (Id2) given above, the ADC has a DAR of 3 (three drug molecules per antibody molecule ). As set forth herein, such ADCs can be generated by introducing mutations into one or more hinge region cysteines of human IgG1 (eg, 1 hinge cysteine), human IgG2 (eg, 3 hinge cysteines), human IgG3 (eg, 10 hinge cysteine residues) or human IgG4 (eg, 1 hinge cysteine residue).

In certain embodiments of the antibody-drug conjugate of formula (Id2), where the multichain antibody contains mutations in one or more cysteine residues in the hinge regions of two heavy chains, the antibody-drug conjugate has the following formula:

wherein each multi-chain antibody heavy chain is designated by the letter H and each multi-chain antibody light chain is designated by the letter L. For the antibody-drug conjugate embodiments of formula (Id2) given above, the ADC has a DAR of 2 (two drug molecules per antibody molecule ). As set forth herein, such ADCs can be generated by introducing mutations into one or more of the hinge region cysteines of human IgG1 (e.g., 2 hinge cysteines), human IgG2 (e.g., 4 hinge cysteines), human IgG3 (eg, 11 hinge cysteine residues) or human IgG4 (eg, 2 hinge cysteine residues). In certain embodiments of the antibody-drug conjugate of formula (Id2), L is a non-cleavable linker.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), L is:

-(CH ₂ ) _m C(O)-,

-(CH ₂ CH ₂ O) _p (CH ₂ CH ₂ )C(O)- or

-(CH ₂ CH ₂ )(OSH ₂ CH ₂ ) _p C(O)-;

where m is equal to an integer from 5 to 11, and p is equal to an integer from 1 to 3.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), L is a cleavable linker.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), L is:

-(CH ₂ ) _m C(O)-Val-Ala-PAB-C(O)-,

-(CH ₂ ) _m C(O)-Val-Cit-PAB-C(O)-,

-(CH ₂ CH ₂ O) _p (CH ₂ CH ₂ )C(O)-Val-Ala-PAB-C(O)-,

-(CH ₂ CH ₂ O) _p (CH ₂ CH ₂ )C(O)-Val-Cit-PAB-C(O)-,

-(CH ₂ CH ₂ )(OCH ₂ CH ₂ ) _p C(O)-Val-Ala-PAB-C(O)- or

-(CH ₂ CH ₂ )(OCH ₂ CH ₂ ) _p C(O)-Val-Cit-PAB-C(O)-;

where m is equal to an integer from 5 to 11, and p is equal to an integer from 1 to 3; And

where RAV has the following structure:

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), CTX is MMAF. In certain embodiments, CTX is MMAE. In certain embodiments, CTX is PDB.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), n is 2, 3 or 4.

In certain embodiments of the antibody-drug conjugate of formula (Id), (Id1) or (Id2), CTX is MMAF and L is -( _CH2 ) _5C (O)-. In certain embodiments, CTX is MMAE and L is -(CH ₂ ) ₅ C(O)-Val-Ala-PAB-OC(O)-. In certain embodiments, CTX is PBD and L is -(CH ₂ ) ₅ C(O)-Val-Ala-, -(CH ₂ ) ₅ C(O)-Val-Cit-, -(CH ₂ ) ₅ C(O)-Val-Ala-PAB-OC(O)- or -(CH ₂ ) ₅ C(O)-Val-Cit-PAB-OC(O)-.

METHODS FOR OBTAINING ADC

Methods for producing ADCs include the use of linker-cytotoxin conjugates and antibody molecules with mutations in the hinge regions.

Possible DAR (drug/antibody ratio) values desired for an ADC include, for example, a DAR of 2, 3, or 4. For example, the following schemes illustrate general schemes for preparing homogeneous ADCs with a DAR of 2, 3, or 4, as set forth herein, which can be obtained by the methods set forth herein.

For example, for an IgG1 ADC, one or both cysteine residues of the hinge region may be mutated to another amino acid (eg, alanine) to produce an ADC with a DAR of 3 or 2 , respectively.

For example, for an IgG2 antibody ADC, two, three, or four cysteine residues of the hinge region may be mutated to another amino acid (eg, alanine) to produce an ADC with a DAR of 4, 3, or 2, respectively.

For example, for an IgG3 antibody ADC, nine, ten, or eleven cysteine residues of the hinge region may be mutated to another amino acid (eg, alanine) to produce an ADC with a DAR of 4, 3, or 2, respectively.

As another example, for an IgG4 ADC, one or both cysteine residues of the hinge region may be mutated to another amino acid (eg, alanine) to produce an ADC with a DAR of 3 or 2, respectively.

General illustrative circuits for obtaining an ADC with a PAR of 2 or 3

A. Preparation of mutants in the hinge region

B. Conjugation

The human IgG1 and IgG4 heavy chain hinge regions contain two cysteine residues, while the human IgG3 heavy chain hinge region contains eleven cysteine residues and the human IgG4 heavy chain hinge region contains four cysteine residues (see Table A).

Hinge region IgG mutants were generated by introducing a mutation at one or both cysteine residues in the hinge region and replacing them with structurally related amino acids, such as alanines. Residues in the hinge region are numbered using Eu numbering for IgG1 (Burton DR (1985) Immunoglobulin G: functional sites. Mol. Immunol., 22: 161-206). Tables B-E align the following numberings: unique IMGT numbering for C-DOMAIN, IMGT numbering for exons, Ei numbering and Kabat numbering for IgG1 (Table B), IgG2 (Table C), IgG3 (Table D) and IgG4 (Table E) person.

(1) J00228 corresponds to the IGHG1*01 allele (allele alignment: human IGHG1) and the G1m1.17 chain (G1m allotypes). The Eu gamma1 chain is encoded by the IGHG1*03 allele (CH1 K120>R, CH3 D12>E and L14>M) and is a G1m3 chain (G1m allotypes).

(2) The CH2 exons IGHG1, IGHG3 and IGHG4 encode 110 amino acids. The CH2 exon IGHG2 encodes 109 amino acids due to the presence of a 3-nucleotide deletion corresponding to codon 3 (position 1.4 according to the unique IMGT numbering for C-DOMAINS).

(3) The last two amino acids of the CH3 exons of IGHG cause CHS (contact hypersensitivity), which is encoded by the C-terminus of the heavy chain present in secreted immunoglobulins.

(4) In Kabat [2], the Eu index for amino acids 219 to 221 should be aligned with the Eu protein (page 671). As a consequence, provisions 232, 233 and 234 correspond to provisions under EE index 219, 220 and 221, respectively (pages 670-678).

(5) MGT (Description View) marks are written in capital letters.

Links:

[1] Edelman G.M. et al., Proc. Natl. Acad. USA, 63, 78-85 (1969). PMID: 5257969.

[2] Kabat E.A. et al. Sequences of proteins of immunological interest. 5th Edition - US Department of Health and Human Services, NIH publication, No. 91-3242, pp. 662, 680, 689 (1991).

LINKER-CYTOTOXIN CONJUGATES

In another aspect, linker-cytotoxin conjugates of formulas (IIa), (IIb) and (IIc) below are provided for use with the antibodies described herein:

And

or an enantiomer, diastereomer or mixtures thereof;

Where:

L is a cleavable or non-cleavable linker; And

CTX is a cytotoxin linked to an L amide bond or carbamate bond.

In certain embodiments of the linker-cytotoxin conjugate of formula (IIa), (IIb) or (IIc), L is a non-cleavable linker.

In certain embodiments of a linker-cytotoxin conjugate of formula (IIa), (IIb) or (IIc), L is:

-(CH ₂ ) _m C(O)-,

-(CH ₂ CH ₂ O) _p (CH ₂ CH ₂ )C(O)- or

-(CH ₂ CH ₂ )(OSH ₂ CH ₂ ) _p C(O)-;

where m is equal to an integer from 5 to 11, and p is equal to an integer from 1 to 3.

In certain embodiments of a linker-cytotoxin conjugate of formula (IIa), (IIb) or (IIc), L is a cleavable linker.

In certain embodiments of a linker-cytotoxin conjugate of formula (IIa), (IIb) or (IIc), L is:

-(CH ₂ ) _m C(O)-Val-Ala-PAB-C(O)-,

-(CH ₂ ) _m C(O)-Val-Cit-PAB-C(O)-,

-(CH ₂ CH ₂ O) _p (CH ₂ CH ₂ )C(O)-Val-Ala-PAB-C(O)-,

-(CH ₂ CH ₂ O) _p (CH ₂ CH ₂ )C(O)-Val-Cit-PAB-C(O)-,

-(CH ₂ CH ₂ )(OCH ₂ CH ₂ ) _p C(O)-Val-Ala-PAB-C(O)- or

-(CH ₂ CH ₂ )(OCH ₂ CH ₂ ) _p C(O)-Val-Cit-PAB-C(O)-;

where m is equal to an integer from 5 to 11, and p is equal to an integer from 1 to 3; And

where RAV has the following structure:

In certain embodiments of the linker-cytotoxin conjugate of formula (IIa), (IIb) or (IIc), CTX is auristatin. In certain embodiments, CTX is MMAF. In certain embodiments, CTX is MMAE. In certain embodiments, CTX is PBD. In certain embodiments, CTX is calicheamicin, doxorubicin, camptothecin, duocarmycin, DM1, DM4, maytansinoid, or tubulisin.

In certain embodiments of a linker-cytotoxin conjugate of formula (IIa), (IIb) or (IIc), wherein CTX is MMAE, L is a cleavable linker.

In certain embodiments of a linker-cytotoxin conjugate of formula (IIa), (IIb) or (IIc), wherein CTX is MMAE, L is -(CH ₂ ) _m C(O)-Val-Ala-PAB-OC(O) - or -(CH ₂ ) _m C(O)-Val-Cit-PAB-OC(O)-, where m is an integer from 5 to 11.

In certain embodiments of a linker-cytotoxin conjugate of formula (IIa), (IIb) or (IIc), wherein CTX is MMAE, L is -(CH ₂ ) ₅ C(O)-Val-Ala-PAB-OC(O) - or -(CH2) ₅ C(O)-Val-Cit-PAB-OC(O)-.

In certain embodiments of a linker-cytotoxin conjugate of formula (IIa), (IIb) or (IIc), wherein CTX is a PBD, L is a cleavable linker.

In certain embodiments of a linker-cytotoxin conjugate of formula (IIa), (IIb) or (IIc), wherein CTX is PBD, L is -(CH ₂ ) _m C(O)-Val-Ala-PAB-OC(O) - or -(CH ₂ ) _m C(O)-Val-Cit-PAB-OC(O)-, where m is an integer from 5 to 11.

In certain embodiments of _{a linker-cytotoxin conjugate of formula (IIa), (IIb) or (IIc), wherein CTX is PBD, L is -(CH2)5C (} O)-Val-Ala-PAB-OC(O) - or -(CH ₂ ) ₅ C(O)-Val-Cit-PAB-OC(O)-.

In certain embodiments, the linker-cytotoxin conjugate has the following structure:

In certain embodiments, the linker-cytotoxin conjugate has the following structure:

In certain embodiments, the linker-cytotoxin conjugate has the following structure:

In certain embodiments, the linker-cytotoxin conjugate has the following structure:

In certain embodiments, the linker-cytotoxin conjugate has the following structure:

In certain embodiments, the linker-cytotoxin conjugate has the following structure:

In certain embodiments, the linker-cytotoxin conjugate has one of the following structures:

And

In certain embodiments, the linker-cytotoxin conjugate has one of the following structures:

And

In certain embodiments, the linker-cytotoxin conjugate has one of the following structures:

And

PHARMACEUTICAL COMPOSITIONS

Therapeutic compositions containing one or more antibodies provided herein can be prepared for storage by mixing the antibody having the desired purity with optional physiologically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences (1990) Mack Publishing Co., Easton , PA) in the form of lyophilized compositions or aqueous solutions. Acceptable carriers, excipients or stabilizers are non-toxic to recipients at the dosages and concentrations used and include buffers such as phosphate, citrate and other organic acids; antioxidants, including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzylammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol; butyl or benzyl alcohol; alkylparabens such as methyl or propylparaben; catechol; resorcinol; cyclohexanol; 3-pentanol and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine or lysine; monosaccharides, disaccharides and other carbohydrates, including glucose, mannose or dextrins; chelating agents such as ethylenediaminetetraacetic acid (EDTA); sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counterions such as sodium ion; metal complexes (eg Zn-protein complexes); and/or non-ionic surfactants such as TWEEN™, PLURONIC™ or polyethylene glycol (PEG).

In addition, the antibodies proposed in this application can, for example, be incorporated into liposomes. Liposomes containing the molecule of interest are prepared by methods known in the art, such as those described by Epstein et al. (1985) Proc, Natl. Acad. Sci. USA, 82: 3688; Hwang et al. (1980) Proc. Natl. Acad. Sci. USA, 77: 4030; and US Pat. Nos. 4,485,045 and 4,544,545. Liposomes with extended residence time in the bloodstream are described in US Pat. No. 5,013,556.

In particular, useful immunoliposomes with a lipid composition that includes phosphatidylcholine, cholesterol and a derivative of phosphatidylethanolamine and PEG (PEG-PE) can be formed by reverse phase evaporation. Liposomes are pressed through filters with pores of a certain size, obtaining liposomes of the desired diameter. Fab' fragments of the antibody provided herein can be conjugated to liposomes as described in Martin et al. (1982) J. Biol. Chem., 257: 286-288, via a disulfide exchange reaction. A chemotherapeutic agent (such as doxorubicin) is possibly contained within the liposome; see Gabizon et al, (1989) J. National Cancer Inst. 81(19): 1484.

Compositions, such as those described herein, may also contain more than one active compound that is needed for the particular indication being treated. In certain embodiments, the compositions contain an antibody provided herein and one or more active compounds with complementary activities that do not adversely affect each other. Accordingly, such molecules are presented in combination in amounts that are effective for the intended purpose. For example, an antibody provided herein may be combined with one or more other therapeutic agents. Such combination therapy may be administered to a patient intermittently or together or sequentially.

The antibody proposed in this application can also be enclosed in a microcapsule prepared, for example, by coacervation or interfacial polymerization methods, for example, in a hydroxymethylcellulose or gelatin microcapsule and a poly(methyl methacrylate) microcapsule, respectively; in colloidal drug delivery systems (eg, liposomes, albumin microspheres, microemulsions, nanoparticles and nanocapsules) or in macroemulsions. Such methods are described in Remington's Pharmaceutical Sciences, (1990) Mack Publishing Co., Easton, PA.

Compositions intended for use by in vivo administration must be sterile. This is easily achieved by filtration, for example through sterilizing filtration membranes.

Extended-release formulations can also be made. Suitable examples of sustained release formulations include semi-permeable matrices of solid hydrophobic polymers containing a polypeptide, the matrices being in the form of extruded articles such as films or microcapsules. Examples of sustained release matrices include matrices of polyesters, hydrogels (eg, poly-2-hydroxyethyl methacrylate or polyvinyl alcohol), polylactides (US Pat. No. 3,773,919), copolymers of L-glutamic acid and ethyl-L-glutamate, non-degradable ethylene vinyl acetate , degradable lactic acid-glycolic acid copolymers such as LUPRON DEPOT™ (injectable microspheres consisting of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3-hydroxybutyric acid. While polymers such as ethylene vinyl acetate and lactic acid-glycolic acid polymers allow release of molecules over 100 days, certain hydrogels release proteins over shorter periods of time. When encapsulated antibodies remain in the body for a long time, they may denature or aggregate as a result of exposure to the aqueous environment at 37°C, resulting in loss of biological activity and possible changes in immunogenicity. Depending on the mechanism involved, rational strategies for stabilization can be developed. For example, if the mechanism of aggregation is found to be the formation of intermolecular S--S bonds via thiodisulfide exchange, then stabilization can be achieved through modification of sulfhydryl residues, lyophilization from acid solutions, control of moisture content, use of appropriate excipients and development of specific compositions based on polymer matrices.

In some embodiments, the pharmaceutical compositions provided herein contain therapeutically effective amounts of one or more antibodies provided herein, and optionally one or more additional prophylactic or therapeutic agents, in a pharmaceutically acceptable carrier. Such pharmaceutical compositions are useful in preventing, treating, or alleviating one or more symptoms of a C10orf54-mediated disease.

Pharmaceutical carriers suitable for administering the compounds provided herein include any such carriers known to those skilled in the art as suitable for the particular route of administration.

In addition, the antibodies provided herein may be formulated as a single pharmaceutically active ingredient or may be combined with other active ingredients (such as one or more other prophylactic or therapeutic agents).

These compositions may contain one or more antibodies proposed in this application. In one embodiment, the antibodies are formulated into suitable pharmaceutical preparations, such as solutions, suspensions, tablets, dispersible tablets, pills, capsules, powders, sustained release formulations or elixirs for oral administration, or sterile solutions or suspensions for parenteral administration, and the drug is in the form of a transdermal patch and dry powder inhalers. In one embodiment, pharmaceutical compositions are prepared from the antibodies described above using methods and techniques well known in the art (see, for example, Ansel (1985) Introduction to Pharmaceutical Dosage Forms. ^4th ed., p. 126).

In certain embodiments of the compositions, one or more antibodies or derivatives thereof are admixed in effective concentrations with a suitable pharmaceutically acceptable carrier. In specific embodiments, the content of the compounds in the compositions is effective to deliver an amount, upon administration, that treats, prevents, or ameliorates a C10orf54-mediated disease or symptom thereof.

In one embodiment, the compositions are formulated for administration as a single dose. To prepare the composition, a weight fraction of the compound at an effective concentration is dissolved, suspended, dispersed in, or otherwise mixed with a selected vehicle to provide relief, prevention of the condition being treated, or amelioration of one or more symptoms.

In some embodiments, the antibody provided by this invention is administered to a pharmaceutically acceptable carrier in an effective amount sufficient to provide a therapeutically beneficial effect in the absence of undesirable side effects in the patient being treated. The therapeutically effective concentration can be determined empirically by testing compounds in in vitro and in vivo systems using routine methods and then extrapolating these data to human dosages.

The content of the antibody in the pharmaceutical composition will depend, for example, on the physicochemical characteristics of the antibody, the dosage regimen and the amount administered, as well as other factors known to those skilled in the art.

In one embodiment, a therapeutically effective dosage provides a serum antibody concentration of from about 0.1 ng/ml to about 50-100 μg/ml. Pharmaceutical compositions, in another embodiment, provide a dosage of from about 0.001 mg to about 2000 mg of antibody per kilogram of body weight per day. Pharmaceutical unit dosage forms can be prepared to provide from about 0.01 mg; 0.1 mg or 1 mg to approximately 500 mg; 1000 mg or 2000 mg; and in one embodiment, from about 10 mg to about 500 mg of antibody and/or a combination of other possible necessary ingredients per unit dosage form.

The antibody drug may be administered at one time or may be divided into several smaller doses to be administered at intervals. Obviously, the exact dosage and duration of treatment depend on the disease being treated and can be determined empirically using known testing protocols or by extrapolation from in vivo or in vitro testing data. It should be noted that concentrations and dosages may also vary depending on the severity of the condition being treated. It should also be understood that for any particular subject, specific dosage regimens may be adjusted over time based on the individual needs and professional judgment of the person administering or supervising the administration of the compositions, and that the concentration ranges stated herein are only representative and are not intended to to limit the scope or practical application of the claimed compositions.

Once the antibody is mixed or added, the resulting mixture may be a solution, suspension, emulsion, or the like. The form of the resulting mixture depends on a number of factors, including the intended route of administration and the solubility of the compound in the chosen vehicle or diluent. The effective concentration is sufficient to reduce the symptoms of the disease, disorder or condition being treated and can be determined empirically.

In some embodiments, pharmaceutical compositions are provided for administration to humans and animals in unit dosage forms, such as tablets, capsules, pills, powders, granules, sterile parenteral solutions or suspensions, and oral solutions or oil-in-water suspensions and emulsions containing suitable amounts of the compounds or pharmaceutically acceptable derivatives thereof. The antibody, in one embodiment, is prepared and administered in single-dose dosage forms or multi-dose dosage forms. The term “single-dose dosage forms” as used herein refers to physically discrete units suitable for human and animal subjects and individually packaged as is known in the art. Each dosage unit contains a predetermined amount of antibody sufficient to produce the desired therapeutic effect, together with the necessary pharmaceutical carrier, excipient or diluent. Examples of single-dose dosage forms include ampoules and syringes and individually packaged tablets or capsules. Single-dose dosage forms can be administered in fractions or multiples. A “multi-dose dosage form” is a plurality of identical single-dose dosage forms packaged in a single container, administered in a separate single-dose dosage form. Examples of multi-dose dosage forms include vials, tablet or capsule bottles, or pint or gallon bottles. Therefore, a multi-dose dosage form is a plurality of single-dose forms that are contained in a single package.

In specific embodiments, one or more anti-C10orf54 antibodies provided herein are included in a liquid pharmaceutical composition. Liquid pharmaceutical compositions for administration can be prepared, for example, by dissolving, dispersing or otherwise mixing the active compound as defined above and possible pharmaceutical adjuvants in a carrier such as, for example, water, saline, aqueous dextrose, glycerin, glycols, ethanol and the like, thereby forming a solution or suspension. If desired, the pharmaceutical composition to be administered may also contain minor amounts of non-toxic excipients such as wetting agents, emulsifying agents, solubilizing agents, pH maintaining agents and the like, for example, acetic acid salts, sodium citrate, cyclodextrin derivatives, sorbitan monolaurate , triethanolamine, sodium acetate, triethanolamine oleate and other similar agents.

Current methods for preparing such dosage forms are known or will be apparent to those skilled in the art; for example, see Remington's Pharmaceutical Sciences (1990) Mack Publishing Co., Easton, PA.

Dosage forms or compositions can be prepared containing the antibody in the range of 0.005% to 100%, with the remainder being composed of a non-toxic carrier. Methods for preparing such compositions are known to those skilled in the art.

Pharmaceutical dosage forms for oral administration are either in solid, gel or liquid form. Solid dosage forms include tablets, capsules, granules and bulk powders. Types of oral tablets include compressed tablets, chewable lozenges, and tablets that may be enteric-coated, sugar-coated, or film-coated. Capsules may be hard or soft gelatin capsules, while granules and powders may be offered in non-effervescent or effervescent form containing a combination of other ingredients known to those skilled in the art.

In certain embodiments, the compositions are dosage forms in solid form. In certain embodiments, the compositions are capsules or tablets. Tablets, pills, capsules, lozenges and the like may contain one or more of the following ingredients or compounds of a similar nature: a binder; lubricant; diluent; glidant; baking powder; dye; sweetener; flavoring; moisturizing agent; vomit-inducing coating and film coating. Examples of binders include microcrystalline cellulose, gum tragacanth, glucose solution, gum acacia, gelatin solution, molasses, polyvinylpyrrolidine, povidone, crospovidones, sucrose and starch paste. Lubricants include talc, starch, magnesium or calcium stearate, lycopodium and stearic acid. Diluents include, for example, lactose, sucrose, starch, kaolin, salt, mannitol and dicalcium phosphate. Glidants include, but are not limited to, colloidal silicon dioxide. Disintegrants include croscarmellose sodium, sodium starch glycolate, alginic acid, corn starch, potato starch, bentonite, methyl cellulose, agar and carboxymethyl cellulose. Dyes include, for example, any approved certified water-soluble dyes for use in foods, drugs and cosmetics (FD&C dyes), mixtures thereof; and water-insoluble FD and C dyes suspended in alumina hydrate. Sweeteners include sucrose, lactose, mannitol and artificial sweeteners such as saccharin, and any number of spray-dried flavors. Flavors include natural flavors extracted from plants, such as fruits, and mixtures of synthetic compounds that produce a pleasant taste sensation, such as, but not limited to, peppermint oil and methyl salicylate. Wetting agents include propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate and polyoxyethylene lauryl ether. Emetic coatings include fatty acids, grease, waxes, shellac, ammonia shellac, and cellulose acetate phthalates. Film coatings include hydroxyethylcellulose, sodium carboxymethylcellulose, polyethylene glycol 4000, and cellulose acetate phthalate.

The antibodies provided herein may be formulated in a composition that protects them from the acidic environment of the stomach. For example, the composition may be formulated with an enteric coating that maintains its integrity in the stomach and allows release of the active compound in the intestines. The composition may also be formulated in combination with an acid neutralizing agent or other such ingredient.

When the unit dosage form is a capsule, it may contain, in addition to a substance of the type described above, a liquid carrier such as a fixed oil. In addition, unit dosage forms may contain various other materials that modify the physical form of the dosage unit, such as sugar coatings and other enteric solubilizing agents. The compounds may also be administered as a component of an elixir, suspension, syrup, cachet, burst capsule, chewing gum, or the like. In addition to the active compound, syrup may contain sucrose as a sweetener and some preservatives, dyes and coloring agents and flavorings.

The antibody can also be mixed with other active substances that do not impair the desired effect, or with substances that complement the desired effect, such as antacids, H2-blockers and diuretics. The active ingredient is an antibody or a pharmaceutically acceptable derivative thereof as described herein. The active ingredient may be included in higher concentrations, up to about 98% by weight.

In all embodiments, compositions in the form of tablets and capsules may be coated with coatings known to those skilled in the art to modify or promote dissolution of the active ingredient. For example, they can be coated with traditional enteric coatings such as phenyl salicylate, waxes and cellulose acetate phthalate.

In specific embodiments, the compositions are liquid dosage forms. Liquid dosage forms for oral administration include aqueous solutions, emulsions, suspensions, solutions and/or suspensions obtained by reconstitution from non-effervescent granules, and effervescent preparations obtained by reconstitution from effervescent granules. Aqueous solutions include, for example, elixirs and syrups. Emulsions are oil-in-water or water-in-oil emulsions.

Elixirs are clear, sweetened, hydroalcoholic preparations. Pharmaceutically acceptable carriers used in elixirs include solvents. Syrups are concentrated aqueous solutions of sugar, such as sucrose, and may contain a preservative. An emulsion is a two-phase system in which one liquid is dispersed in the form of small droplets in another liquid. Pharmaceutically acceptable carriers used in emulsions include non-aqueous liquids, emulsifying agents and preservatives. Pharmaceutically acceptable suspending agents and preservatives are used in suspensions. Pharmaceutically acceptable substances used in the non-effervescent granules to be reconstituted into a liquid oral dosage form include diluents, sweeteners and wetting agents. Pharmaceutically acceptable substances used in the effervescent granules to be reconstituted into a liquid oral dosage form include organic acids and a source of carbon dioxide. Colors and flavors are used in all of the above dosage forms.

Solvents include glycerin, sorbitol, ethyl alcohol and syrup. Examples of preservatives include glycerin, methyl and propyl paraben, benzoic acid, sodium benzoate and alcohol. Examples of non-aqueous liquids used in emulsions include mineral oil and cottonseed oil. Examples of emulsifying agents include gelatin, gum acacia, tragacanth, bentonite, and surfactants such as hydroxylene sorbitan monooleate. Suspending agents include sodium carboxymethylcellulose, pectin, tragacanth, veegum and gum acacia. Sweeteners include sucrose, syrups, glycerin and artificial sweeteners such as saccharin. Wetting agents include propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate and polyoxyethylene lauryl ether. Organic acids include citric and tartaric acid. Sources of carbon dioxide include sodium bicarbonate and sodium carbonate. Dyes include any approved certified water-soluble FD and C dyes and mixtures thereof. Flavors include natural flavors extracted from plants, such as fruits, and mixtures of synthetic compounds that produce a pleasant taste sensation.

To prepare a solid dosage form, in one embodiment, a solution or suspension, for example, in propylene carbonate, vegetable oils or triglycerides, is encapsulated in a gelatin capsule. Such solutions and their preparation and encapsulation are described in US Pat. Nos. 4,328,245, 4,409,239, and 4,410,545. To prepare a liquid dosage form, a solution, for example, in polyethylene glycol, can be diluted with a sufficient amount of a pharmaceutically acceptable liquid carrier, such as water, so that it is easily measure for insertion.

Alternatively, liquid or semi-solid compositions for oral administration can be prepared by dissolving or dispersing the active compound or a salt thereof in vegetable oils, glycols, triglycerides, propylene glycol esters (eg, propylene carbonate) and other similar vehicles and encapsulating these solutions or suspensions in solid shells. or soft gelatin capsules. Other useful compositions include those set forth in US Patent Nos. RE28819 and 4358603. Briefly, such compositions include, but are not limited to, compositions containing the compound provided herein, dialkylated mono- or polyalkylene glycol, including but not limited to these, 1,2-dimethoxymethane, diglyme, triglyme, tetraglyme, polyethylene glycol dimethyl ether-350, polyethylene glycol dimethyl ether-550, polyethylene glycol dimethyl ether-750, where 350, 550 and 750 refer to the approximate average molecular weight of polyethylene glycol, and one or more antioxidants such as butylated hydroxy toluene (BHT), butylated hydroxyanisole (BHA), propyl gallate, vitamin E, hydroquinone, hydroxycoumarin, ethanolamine, lecithin, cephalin, ascorbic acid, malic acid, sorbitol, phosphoric acid, thiodipropionic acid acid and its esters and dithiocarbamates.

Other compositions include, but are not limited to, aqueous alcoholic solutions containing a pharmaceutically acceptable acetal. Alcohols used in these compositions are any pharmaceutically acceptable water-miscible solvents having one or more hydroxyl groups, including, but not limited to, propylene glycol and ethanol. Acetals include, but are not limited to, di(lower alkyl) acetals (lower alkyl) aldehydes, such as acetaldehyde diethyl acetal.

Parenteral administration, in one embodiment, is characterized by injection, and either subcutaneous, intramuscular, or intravenous administration is also covered herein. Injectable preparations may be prepared in conventional forms, either as solutions or suspensions in liquid, or as solid forms suitable for solution or suspension in liquid before injection, or as emulsions. Injectable preparations, solutions and emulsions also contain one or more excipients. Suitable excipients are, for example, water, saline, dextrose, glycerol or ethanol. In addition, if desired, the pharmaceutical compositions to be administered may also contain minor amounts of non-toxic excipients such as wetting or emulsifying agents, pH maintaining agents, stabilizers, solubility enhancers and other similar agents such as, for example, sodium acetate, sorbitan monolaurate , triethanol aminooleate and cyclodextrins.

Implantation of a slow release or sustained release system to maintain a constant dosage level (see, for example, US Pat. No. 3,710,795) is also included herein. Briefly, the compound of this invention is dispersed in a solid internal matrix, for example, polymethyl methacrylate, polybutyl methacrylate, plasticized or unplasticized polyvinyl chloride, plasticized nylon, plasticized polyethylene terephthalate, natural rubber, polyisoprene, polyisobutylene, polybutadiene, polyethylene, ethylene-vinyl acetate copolymers, orikon rubbers, polydimethylsiloxanes, silicone carbonate copolymers, hydrophilic polymers such as acrylic and methacrylic acid ester hydrogels, collagen, cross-linked polyvinyl alcohol and cross-linked partially hydrolyzed polyvinyl acetate, which (matrix) is surrounded by an outer polymer membrane, e.g. polyethylene, polypropylene , ethylene/propylene copolymers, ethylene/ethyl acrylate copolymers, ethylene/vinyl acetate copolymers, silicone rubbers, polydimethylsiloxanes, neoprene rubber, chlorinated polyethylene, polyvinyl chloride, vinyl chloride-vinyl acetate copolymers, vinylidene chloride, ethylene and propylene, and containing polyethylene terephthalate, butyl rubber , epichlorohydrin rubbers, ethylene/vinyl alcohol copolymer, ethylene/vinyl acetate/vinyl alcohol terpolymer and ethylene/vinyloxyethanol copolymer, which (membrane) is insoluble in body fluids. The antibody diffuses through the outer polymer membrane during the release step at a controlled rate. The amount of antibody contained in such parenteral compositions depends greatly on its specific nature, as well as the activity of the compound and the needs of the subject.

Preparations for parenteral administration include sterile solutions ready for injection, sterile dry soluble products such as lyophilized powders ready for combination with a vehicle immediately before use, including tablets for subcutaneous injection, sterile suspensions ready for injection, sterile dry insoluble products , ready to be combined with a diluent immediately before use, and sterile emulsions. Solutions can be either aqueous or non-aqueous.

For intravenous administration, suitable carriers include saline or phosphate buffered saline (PBS) and solutions containing thickening and solubilizing agents such as glucose, polyethylene glycol and polyethylene glycol and propylene glycol and mixtures thereof.

Pharmaceutically acceptable carriers used in parenteral formulations include aqueous diluents, non-aqueous diluents, antimicrobial agents, isotonic agents, buffers, antioxidants, local anesthetics, suspending and dispersing agents, emulsifying agents, complexing or chelating agents and other pharmaceutically acceptable agents.

Examples of aqueous diluents include sodium chloride injection, Ringer's solution for injection, isotonic dextrose injection, sterile water for injection, dextrose-lactated Ringer's solution for injection. Non-aqueous parenteral diluents include fixed oils of vegetable origin, cottonseed oil, corn oil, sesame oil and peanut oil. Antimicrobial agents in bacteriostatic or fungistatic concentrations may be added to parenteral preparations packaged in multi-dose containers, which include phenols or cresols, mercuric compounds, benzyl alcohol, chlorobutanol, p-hydroxybenzoic acid methyl and propyl esters, thimerosal, benzalkonium chloride, and benzethonium chloride. Isotonic agents include sodium chloride and dextrose. Buffers include phosphate and citrate buffers. Antioxidants include sodium bisulfate. Local anesthetics include procaine hydrochloride. Suspending and dispersing agents include sodium carboxymethylcellulose, hydroxypropylmethylcellulose and polyvinylpyrrolidone. Emulsifying agents include polysorbate 80 ( ^TWEEN® 80). The metal ion complexing or chelating agent includes EDTA. Pharmaceutically acceptable carriers also include ethyl alcohol, polyethylene glycol and propylene glycol for water miscible diluents and sodium hydroxide, hydrochloric acid, citric acid or lactic acid for pH adjustment.

The concentration of the pharmaceutically active compound is adjusted so that, after injection, an effective amount is achieved to obtain the desired pharmacological effect. The exact dose depends on the age, weight and condition of the patient or animal, which is known in the art.

Single-dose parenteral medications may be packaged in an ampoule, vial, or syringe with a needle. All preparations for parenteral administration may be sterile, as is known and practiced in the art.

By way of illustration, intravenous or intraarterial infusion of a sterile aqueous solution containing the active compound is considered an effective route of administration. Another embodiment is a sterile aqueous or oily solution, or a sterile suspension in water or oil, containing the active substance, administered by injection as needed to obtain the desired pharmacological effect.

Injectable drugs are intended for local and systemic administration. In one embodiment, the drug in a therapeutically effective dosage is formulated such that in the tissue(s) being treated, the active compound is contained in a concentration of at least about 0.1% w/w. up to about 90% w/w or more, in certain embodiments, more than 1% w/w.

The antibody may be suspended into a micronized or other suitable form. The form of the resulting mixture depends on a number of factors, including the intended route of administration and the solubility of the compound in the chosen vehicle or diluent. The effective concentration is sufficient to reduce the symptoms of the condition and can be determined empirically.

In other embodiments, the pharmaceutical compositions are lyophilized powders that can be reconstituted for administration as solutions, emulsions, and other mixtures. In addition, they can be re-diluted and based on them, compositions can be prepared in the form of solids or gels.

The lyophilized powder is prepared by dissolving the antibody provided herein, or a pharmaceutically acceptable derivative thereof, in a suitable solvent. In some embodiments, the lyophilized powder is sterile. The solvent may contain an excipient that improves stability or other pharmacological component of the powder or solution prepared by reconstitution from the powder. Excipients that can be used include, but are not limited to, dextrose, sorbitol, fructose, corn syrup, xylitol, glycerin, glucose, sucrose or other suitable agent. The solvent may also contain a buffer, such as a citrate, sodium or potassium phosphate buffer, or other such buffer known to those skilled in the art, in one embodiment at approximately neutral pH. Subsequent sterile filtration of the solution, then lyophilization under standard conditions known to those skilled in the art, provides the desired composition. In one embodiment, the resulting solution will be portioned into vials for lyophilization. Each vial will contain a single dose or multiple doses of the compound. The lyophilized powder can be stored under appropriate conditions, such as at about 4° C. to room temperature.

Reconstitution of this lyophilized powder with water for injection produces compositions for parenteral administration. To effect reconstitution, the lyophilized powder is added to sterile water or other suitable carrier. The exact amount depends on the selected compound. This amount can be determined empirically.

Mixtures for topical use are prepared as described for local and systemic administration. The resulting mixture may be a solution, suspension, emulsion or the like and may be prepared in the form of creams, gels, ointments, emulsions, solutions, elixirs, lotions, suspensions, tinctures, pastes, foams, aerosols, rinses, sprays, suppositories , dressings, skin patches or any other composition suitable for topical administration.

The antibodies provided herein can be formulated into aerosols for topical use, for example by inhalation (see, for example, US Pat. Nos. 4,044,126, 4,414,209, and 4,364,923, which disclose aerosols for the delivery of a steroid hormone useful in the treatment of inflammatory diseases , in particular asthma). These compositions for administration to the respiratory tract may be in the form of an aerosol or nebulizer solution or as a micronized powder for insufflation, alone or in combination with an inert carrier such as lactose. In this case, the particles of the composition will, in one embodiment, have a diameter of less than 50 microns, in one embodiment, less than 10 microns.

Based on these compounds, compositions can be prepared for topical or local use, for example, for topical application to the skin and mucous membranes, such as the eyes, in the form of gels, creams and lotions, and for application to the eye, or for intracisternal or intraspinal use. Topical administration is intended for transdermal delivery, as well as for ocular or mucosal administration, or for inhalation therapies. In addition, nasal solutions of the active compound, alone or in combination with other pharmaceutically acceptable excipients, can be administered.

Such solutions, particularly those intended for ophthalmic use, can be prepared as 0.01% to 10% isotonic solutions, pH approximately 5-7, using appropriate salts.

Other routes of administration, for example, using transdermal patches, including iontophoretic and electrophoretic agents, and rectal administration, are also included in this description.

Transdermal patches, including iontophoretic and electrophoretic agents, are well known to those skilled in the art. For example, such patches are described in US patents No. 6267983, 6261595, 6256533, 6167301, 6024975, 6010715, 5985317, 5983134, 5948433 and 5860957.

For example, pharmaceutical dosage forms for rectal administration include rectal suppositories, capsules and tablets for systemic action. The term "rectal suppositories" as used herein means solid forms for administration to the rectum that melt or soften at body temperature, releasing one or more pharmacologically or therapeutically active ingredients. Pharmaceutically acceptable substances used in rectal suppositories include bases or fillers and melting point elevating agents. Examples of bases include cocoa butter (cocoa bean butter), glycerin-gelatin mixture, Carbowax (polyoxyethylene glycol) and corresponding mixtures of mono-, di- and triglycerides of fatty acids. Combinations of different bases can be used. Agents for increasing the melting point of suppositories include spermaceti and wax. Rectal suppositories can be prepared either by pressing or molding. The weight of the rectal suppository, in one embodiment, is approximately 2-3 grams.

Tablets and capsules for rectal administration can be prepared using the same pharmaceutically acceptable substance and by the same methods as in the case of compositions for oral administration.

Antibodies and other compositions provided herein may also be formulated to target a specific tissue, receptor, or other area of the body of the subject being treated. Many such targeting methods are well known to those skilled in the art. All such targeting methods are included herein for use in the compositions of the present invention. For non-limiting examples of targeting methods, see, for example, US patents No. 6316652, 6274552, 6271359, 6253872, 6139865, 6131570, 6120751, 6071495, 6060082, 6048736, 6039975, 6 004534, 5985307, 5972366, 5900252, 5840674, 5759542 and 5709874.

In one embodiment, liposomal suspensions, including tissue-targeting liposomes such as tumor-targeting liposomes, can also be used as pharmaceutically acceptable carriers. They can be prepared in accordance with methods known to those skilled in the art. For example, liposome compositions can be prepared as described in US Pat. No. 4,522,811. Briefly, liposomes such as multilayer vesicles (MLVs) can be formed by drying egg phosphatidylcholine and brain phosphatidylserine (in a molar ratio of 7:3) on the inner surface of a flask. A solution of the compound provided herein in phosphate buffered saline (PBS) free of divalent cations is added and the flask is shaken until the lipid film is dispersed. The resulting vesicles are washed to remove unencapsulated compound, collected by centrifugation and then resuspended in PBS.

METHODS OF ADMINISTRATION AND DOSES

In addition, this application provides compositions containing one or more antibodies provided herein for use in the prevention, treatment and/or alleviation of one or more than one symptom of a disease, such as a C10orf54-mediated disease.

Certain embodiments of the present invention provide compositions comprising one or more antibodies provided herein for use in inhibiting, preventing, or treating a C10orf54-mediated disease and/or for alleviating one or more symptoms of a C10orf54-mediated disease. Typical C10orf54-mediated diseases include cell proliferation disorder, cancer, tumorigenesis, and graft-versus-host disease (GVHD) or symptoms thereof.

Certain embodiments of the invention provide compositions comprising one or more antibodies provided herein for use in the prevention, treatment and/or alleviation of one or more symptoms of a C10orf54-mediated disease, such as a cell proliferation disorder. Disorders of cell proliferation may include cancer or tumor formation or symptoms thereof. In certain embodiments, impaired cell proliferation is associated with increased expression and/or activity of C10orf54. For example, in certain embodiments, impaired cell proliferation is associated with increased expression of C10orf54 on the surface of the cancer cell. Examples of disorders of cellular proliferation that may be treated, prevented, or ameliorated by the antibodies provided herein include, but are not limited to, cancer of the bladder, breast, colon, connective tissue, rectum, stomach, esophagus, lung, larynx, kidney, oral cavity, ovarian or prostate cancer, or sarcoma, melanoma, glioma, lymphoma or leukemia, or metastases from any of these cancers. Typical disorders of cell proliferation include, but are not limited to, leukemia, either acute or chronic, fibrosarcoma, and bladder cancer.

Leukemias are types of cancer of hematopoietic tissues, characterized by distortion of the proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias are generally classified as either chronic (slowly progressive) or acute (rapidly progressive). Leukemias can be further classified based on the type of blood cells affected. For example, lymphoid cell leukemia includes lymphoid leukemia, lymphocytic leukemia or lymphoblastic leukemia, and myeloid cell leukemia includes myeloid leukemia, myelogenous leukemia, myeloblastic leukemia or granulocytic leukemia. The four major types of leukemia that may be treated, prevented, or ameliorated by the methods proposed herein include acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML), and chronic myeloid leukemia (CML). .

According to one aspect of the present invention, methods are provided for preventing or treating a disease described herein by administering to a subject a therapeutically effective amount of an anti-C10orf54 antibody described herein or a composition thereof. In certain embodiments, a method of treating a disease includes administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising an anti-C10orf54 antibody and a pharmaceutically acceptable carrier or excipient. The method provided herein may also include the use of at least one additional therapeutic agent, such as the agents provided herein, either as a separate treatment or conjugated or recombinantly fused to the anti-C10orf54 antibody provided herein. application.

In one embodiment, the anti-C10orf54 antibody provided herein can be used to target C10orf54 expressed by cancer cells by contacting the antibody with C10orf54 to form an antibody-antigen complex, resulting in a conjugated or recombinant fusion agent described in this application, gains access to the internal contents of the cell. In one embodiment, the bound antibody is internalized by a cancer cell expressing C10orf54.

In certain embodiments, the present invention provides compositions comprising one or more antibodies provided herein for use in the prevention, treatment and/or alleviation of one or more symptoms of a C10orf54-mediated disease, such as GVHD or a symptom thereof. GVHD is commonly observed following the use of allogeneic or inappropriately matched bone marrow grafts (BMT).

In some embodiments, GVHD is acute GVHD. Symptoms of acute GVHD can appear quickly and can be mild or severe. In some cases, acute GVHD develops within about three months after transplantation, for example, when the blood count is restored after transplantation. In some cases, acute GVHD involves the skin, gastrointestinal (GI) tract, and/or liver. For example, in some patients, the cutaneous form of acute GVHD begins with a rash, such as on the patient's palms of the hands, soles of the feet, or shoulders. However, the rash may become widespread and may be itchy and painful and/or may result in blistering and peeling. The hepatic form of acute GVHD can affect normal liver functions, such as affecting liver enzymes, and can in turn cause jaundice. The hepatic form of acute GVHD can also cause the patient's abdomen to become swollen and tender if the liver becomes enlarged. Finally, symptoms of intestinal acute GVHD (or gastrointestinal GVHD) may include diarrhea, mucus or blood in the stool, abdominal cramps or pain, indigestion, nausea, and/or loss of appetite. Other common symptoms of acute GVHD may include anemia, low-grade fever, and/or increased susceptibility to infections. Any combination of such symptoms of acute GVHD can be prevented, treated and/or alleviated using the compositions and methods provided herein.

In other embodiments, GVHD is chronic GVHD. Chronic GVHD can occur for anywhere from about three months to about one year or more after transplantation. Chronic GVHD can be mild or severe and generally includes symptoms similar to acute GVHD. Chronic GVHD may involve the skin and digestive system, including the liver, but may also involve other organs and the immune system (eg, making the patient more susceptible to infections) and/or connective tissues. Symptoms of the cutaneous form of chronic GVHD include rash, dry skin, rough skin, itchy skin, darkening of skin color, thickening of the skin and/or may affect the hair (eg, cause hair loss, graying) or nails (eg, cause hard or brittle nails ). The intestinal form of chronic GVHD can affect the digestive system, oral cavity, esophagus, stomach lining and/or intestinal lining, and symptoms may include diarrhea, dry or irritated mouth, pain when swallowing, poor absorption of nutrients in the stomach, bloating, stomach cramps . The hepatic form of chronic GVHD can cause liver damage and scarring (cirrhosis). Chronic GVHD of the eye can affect the tear-producing glands, causing dry eyes, burning and painful sensations, or difficulty seeing bright light. The pulmonary form of chronic GVHD may cause shortness of breath, wheezing, persistent cough, and/or increase susceptibility to respiratory tract infections. Chronic GVHD affects (eg causes inflammation) the tendons that connect muscle to bone, causing difficulty straightening or bending your arms and legs. Any combination of such symptoms of chronic GVHD can be prevented, treated and/or alleviated using the compositions and methods provided herein.

In certain embodiments, the antibody provided herein can be used, for example, in in vitro, ex vivo and in vivo therapeutic methods. In some embodiments, this application provides methods for inhibiting cell growth or proliferation either in vivo or in vitro, the method comprising contacting the cell with an effective amount of an anti-C10orf54 composition or antibody provided herein. In some embodiments, an antibody provided herein can be used in a method of inducing cell death. The method may include contacting the cell with an effective amount of an anti-C10orf54 composition or antibody provided herein. These methods can be carried out under conditions that allow the antibody to bind to a C10orf54 polypeptide, polypeptide fragment, or epitope, for example, but not limited to, when the C10orf54 polypeptide is expressed on the surface of a cell. When inhibiting cell growth or cell proliferation, such inhibition may include reducing cell growth or proliferation by at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95% or 100% and may include cell death. In certain embodiments, the cell is a cancer cell or precancerous cell. In certain embodiments, the cell is a bladder, breast, colon, connective tissue, rectum, stomach, esophagus, lung, larynx, kidney, oral, ovarian, or prostate cancer cell, or a sarcoma, melanoma, glioma, lymphoma, or leukemia cell. In certain embodiments, the cell is an immune cell expressing a C10orf54 polypeptide, such as, but not limited to, a regulatory T cell (ie, a suppressor T cell).

Antibody to C10orf54 can be administered to humans for therapeutic or prophylactic purposes. In addition, an anti-C10orf54 antibody can be administered to a non-human mammal expressing C10orf54 with which the antibody cross-reacts (eg, primate, pig, rat or mouse), for veterinary purposes or as an animal model of human disease. With regard to the latter, such animal models may be useful for assessing the therapeutic or prophylactic efficacy of antibodies or immunoconjugates proposed herein (eg, testing dosages and time courses of administration).

In certain embodiments, an antibody provided herein can be used in a method of modulating an immune response in a subject. Such methods may include administering an effective amount of a composition containing an antibody provided herein to a subject. In some aspects, modulation may include (a) enhancing T cell activation; (b) increased proliferation of T cells and/or (c) increased production of cytokines. Techniques for immune response modulation assays are well known to one skilled in the art and such assays can be readily performed by one skilled in the art.

In a specific embodiment, a composition for use in inhibiting, preventing, treating and/or alleviating one or more symptoms of a C10orf54-mediated disease comprises an antibody described herein. In another specific embodiment, a composition for use in inhibiting, preventing, treating and/or alleviating one or more symptoms of a C10orf54-mediated disease comprises an antigen binding fragment, fusion protein or functional fragment of an antibody described herein.

In another embodiment, a composition for use in inhibiting, preventing, treating and/or alleviating one or more symptoms of a C10orf54-mediated disease comprises one or more antibodies described herein.

As discussed in more detail elsewhere in this specification, the composition provided herein may be used either alone or in combination with other compounds or compositions. In addition, antibodies can be additionally fused recombinantly at the N- or C-terminus to a heterologous polypeptide or chemically conjugated (including by covalent and non-covalent conjugation methods) to polypeptides or other compounds. For example, the antibodies provided herein can be recombinantly fused or conjugated to molecules useful as labels in detection assays and to effector molecules such as heterologous polypeptides, drugs, radionucleotides or toxins. See, for example, PCT publications WO 92/08495, WO 91/14438, WO 89/12624, US patent No. 5314995 and EP 396387.

The antibodies provided herein can be used, for example, to purify, detect and target C10orf54 antigens in diagnostic and therapeutic methods, both in vitro and in vivo. For example, modified antibodies are used in immunoassays to qualitatively and quantitatively measure C10orf54 levels in biological samples. See, for example, Harlow et al., Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory Press, 2nd ed., 1988) (incorporated herein by reference in its entirety).

This application further provides methods for inhibiting, treating, preventing and/or ameliorating one or more symptoms of a C10orf54-mediated disease by administering to a subject an effective amount of an antibody or a pharmaceutical composition containing an antibody provided herein. In one aspect, the antibody is substantially purified (eg, substantially free of substances that limit its effect or cause unwanted side effects). In specific embodiments, the antibody is a humanized monoclonal antibody. The subject to which the therapeutic agent is administered may be a mammal, such as a non-primate mammal (eg, cattle, pigs, horses, cats, dogs, rats, etc.) or a primate (eg, a monkey such as a cynomolgus macaque , or person). In a particular embodiment, the subject is a person. In another embodiment, the subject is a person with a C10orf54-mediated disease.

Various delivery systems are known and can be used to administer a prophylactic or therapeutic agent (e.g., the antibody provided herein), including, but not limited to, encapsulation in liposomes, microparticles, microcapsules, the use of recombinant cells capable of expressing the antibody, receptor-mediated endocytosis (see, for example, Wu and Wu, J. Biol. Chem., 262: 4429-4432 (1987)), construction of a nucleic acid as part of a retroviral or other vector, etc. Methods of administering a prophylactic or therapeutic agent (e.g., the antibody provided herein) or pharmaceutical composition include, but are not limited to, parenteral (e.g., intradermal, intramuscular, intraperitoneal, intravenous, and subcutaneous), epidural, and mucosal (e.g., intranasal and by oral route). In a specific embodiment, the prophylactic or therapeutic agent (eg, an antibody provided herein) or pharmaceutical composition is administered intranasally, intramuscularly, intravenously, or subcutaneously. Prophylactic or therapeutic agents or compositions can be administered by any convenient route, for example, by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (for example, through the oral mucosa, nasal mucosa, rectal and intestinal mucosa, etc. .d.) and can be administered together with other biologically active agents. Administration may be systemic or local. In addition, pulmonary administration can also be used, for example by using an inhaler or nebulizer and a composition with an aerosolizing agent. See, for example, US Pat. Nos. 6,019,968, 5,985,320, 5,985,309, 5,934,272, 5,874,064, 5,855,913, 5,290,540, and 4,880,078; and PCT Publication Nos. WO 92/19244, WO 97/32572, WO 97/44013, WO 98/31346 and WO 99/66903, each of which is incorporated herein by reference in its entirety.

In a particular embodiment, it may be desirable to locally administer a prophylactic or therapeutic agent or pharmaceutical composition provided herein to the area in need of treatment. This may be achieved, for example, and not by way of limitation, by local infusion, by topical administration (eg, by intranasal spray), by injection, or by use of an implant, which implant may be a porous, non-porous or gel-like material, including membranes , such as silastic membranes or fibers. In certain embodiments, when administering antibodies provided herein, care should be taken when using materials that do not absorb the antibody.

In another embodiment, the therapeutic agent or composition provided herein may be delivered in a vesicle, particularly in a liposome (see Langer, 1990, Science, 249: 1527-1533; Treat et al. in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez-Berestein and Fidler (eds.), Liss, New York, pp. 353-365 (1989); Lopez-Berestein, ibid., pp. 317-327; generally see ibid.).

In another embodiment, a therapeutic agent or composition provided herein may be delivered in a controlled release or sustained release system. In one embodiment, a pump can be used to achieve controlled or sustained release (see Langer, supra; Sefton, 1987, CRC Grit. Ref. Biomed. Eng., 14:20; Buchwald et al., 1980, Surgery, 88:507 ; Saudek et al., 1989, N. Engl. Med., 321: 574). In another embodiment, polymeric materials can be used to achieve controlled or sustained release of a therapeutic agent (eg, an antibody provided herein) or a composition provided herein (see, for example, Medical Applications of Controlled Release, Langer and Wise (eds .), CRC Pres., Boca Raton, Florida (1974); Controlled Drug Bioavailability, Drug Product Design and Performance, Smolen and Ball (eds.), Wiley, New York (1984); Ranger and Peppas, 1983, J. Macromol. Sci. Macromol. Chem., 23: 61; also see Levy et al., 1985, Science, 228: 190; During et al., 25: 351. , 1989, J. Neurolsurg., 71: 105); US Patent No. 5679377; US Patent No. 5916597; US Patent No. 5912015; US Patent No. 5989463; US Patent No. 5128326; PCT publication No. WO 99/15154; and PCT publication No. WO 99/20253. Examples of polymers used in sustained release compositions include, but are not limited to, poly-2-hydroxyethyl methacrylate, polymethyl methacrylate, polyacrylic acid, ethylene vinyl acetate copolymer, polymethacrylic acid, polyglycolides (PLG), polyanhydrides, poly-N-vinylpyrrolidone, polyvinyl alcohol, polyacrylamide, poly and ethylene glycol, polylactides (PLA), polylactide-co-glycolides (PLGA) and polyorthoesters. In a specific embodiment, the polymer used in the sustained release composition is inert, free of leachable impurities, shelf stable, sterile and biodegradable. In yet another embodiment, a controlled or sustained release system may be placed in close proximity to the therapeutic target, such as the nasal passages or lungs, resulting in only a fraction of the systemic dose being required (see, e.g., Goodson, in Medical Applications of Controlled Release , supra, vol. 2, pp. 115-138 (1984). Controlled release systems are discussed in a review by Langer (1990, Science, 249: 1527-1533). To prepare sustained release compositions containing one or more of the antibodies provided herein, any method known to one skilled in the art can be used. See, for example, US Pat. No. 4,526,938, PCT Publication WO 91/05548, PCT Publication WO 96/20698, Ning et al., 1996, "Intratumoral Radioimmunotherapy of a Human Colon Cancer Xenograft Using a Sustained-Release Gel", Radiotherapy & Oncology, 39:179-189, Song et al., 1995, Antibody Mediated Lung Targeting of Long-Circulating Emulsions", PDA Journal of Pharmaceutical Science & Technology, 50: 372-397, Cleek et al., 1997, "Biodegradable Polymeric Carriers for a bFGF Antibody for Cardiovascular Application", Pro. Int'l. Symp. Control. Rel. Bioact. Mater., 24: 853-854 and Lam et al., 1997, "Microencapsulation of Recombinant Humanized Monoclonal Antibody for Local Delivery ", Proc. Int'l. Symp. Control Rel. Bioact. Mater., 24: 759-760.

In a specific embodiment, when a compound provided herein is a nucleic acid encoding a prophylactic or therapeutic agent (e.g., an antibody provided herein), the nucleic acid can be administered in vivo to promote expression of the therapeutic agent it encodes, wherein it is constructed as part of an appropriate nucleic acid expression vector and introduced so that it is inside the cell, for example, through the use of a retroviral vector (see US Pat. No. 4,980,286), or by direct injection, or through the use of microparticle bombardment (for example, using gene guns; Biolistic, Dupont), or by applying a coating of lipids, or cell surface receptors, or transfection agents, or by introducing it in a bound state with a homeobox-like peptide sequence that is known to enter the nucleus (see, for example, Joliot et al., 1991, Proc. Acad. Sci. USA, 88: 1864-1868), etc. Alternatively, for expression, the nucleic acid may be introduced into the cell and incorporated by homologous recombination into the DNA of the host cell.

In a specific embodiment, the composition contains one, two or more antibodies proposed in this application. In another embodiment, the composition contains one, two or more antibodies proposed in this application, and a prophylactic or therapeutic agent other than the antibody proposed in this application. In certain embodiments, these agents are known to be useful or have been or are currently used for the prevention, treatment and/or alleviation of one or more symptoms of a C10orf54-mediated disease. In addition to prophylactic or therapeutic agents, the compositions provided herein may also contain a carrier.

The compositions provided herein include bulk dosage compositions useful in the manufacture of pharmaceutical compositions (eg, compositions suitable for administration to a subject or patient) that can be used to prepare unit dosage forms. In a specific embodiment, the composition proposed in this application is a pharmaceutical composition. Such compositions contain a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic agents (eg, an antibody as provided herein or another prophylactic or therapeutic agent) and a pharmaceutically acceptable carrier. In certain embodiments, the pharmaceutical compositions are formulated to be suitable for a particular route of administration to a subject.

In a specific embodiment, the composition is formulated in accordance with conventional techniques into a pharmaceutical composition adapted for intravenous administration to humans. Typically, compositions for intravenous administration are solutions in sterile isotonic aqueous buffer. If necessary, the composition may also include a solubilizing agent and a local anesthetic, such as lidocaine, to relieve pain at the injection site. Such compositions, however, can be administered by a route other than intravenous administration.

Typically, the ingredients of the compositions provided herein are supplied either separately or mixed together in a unit dosage form, for example, as a dry lyophilized powder or a water-free concentrate in a sealed container such as an ampoule or sachet, indicating the quantity active agent. If the composition is to be administered by infusion, it can be dispensed using an infusion bottle containing sterile pharmaceutical grade water or saline. If such a composition is administered by injection, an ampoule of sterile water for injection or saline should be provided so that the ingredients can be mixed before administration.

In certain embodiments, the antibody provided herein is packaged in a sealed container, such as an ampoule or sachet, indicating the amount of antibody. In one embodiment, the antibody is supplied as a dry, sterile lyophilized powder or water-free concentrate in a sealed container and can be reconstituted, for example, in water or saline to a concentration suitable for administration to a subject. In certain embodiments, the antibody is supplied as a dry, sterile, lyophilized powder in a sealed container in a unit dose of at least 0.1 mg; at least 0.5 mg; at least 1 mg; at least 2 mg; or at least 3 mg; for example, at least 5 mg; at least 10 mg; at least 15 mg; at least 25 mg; at least 30 mg; at least 35 mg; at least 45 mg; at least 50 mg; at least 60 mg; at least 75 mg; at least 80 mg; at least 85 mg; at least 90 mg; at least 95 mg; or at least 100 mg. The lyophilized antibody can be stored at a temperature of 2 to 8°C in its original container, and the antibody can be administered within 12 hours, for example, within 6 hours, within 5 hours, within 3 hours. hours or within 1 hour after repeated dilution. In an alternative embodiment, the antibody in liquid form is supplied in a sealed container indicating the amount and concentration of the antibody. In certain embodiments, the antibody in liquid form is supplied in a sealed container at a concentration of at least 0.1 mg/ml, at least 0.5 mg/ml, or at least 1 mg/ml, such as at least 5 mg/ml. ml, at least 10 mg/ml, at least 15 mg/ml, at least 25 mg/ml, at least 30 mg/ml, at least 40 mg/ml, at least 50 mg/ml, at least 60 mg/ml, at least 70 mg/ml, at least 80 mg/ml, at least 90 mg/ml or at least 100 mg/ml.

The compositions proposed in this application can be prepared in the form of neutral or salt forms. Pharmaceutically acceptable salts include salts formed with anions such as those derived from hydrochloric, phosphoric, acetic, oxalic, tartaric acids, etc., and salts formed with cations such as those derived from sodium hydroxide, potassium hydroxide, ammonium, calcium, ferric iron, cations of isopropylamine, triethylamine, 2-ethylaminoethanol, histidine, procaine, etc.

The amount of a therapeutic agent (eg, an antibody provided herein) or composition provided herein that will be effective in preventing, treating and/or alleviating one or more symptoms of a C10orf54-mediated disease can be determined by standard clinical techniques.

Accordingly, to prevent, treat, and/or alleviate one or more symptoms of a C10orf54-mediated disease, the antibody or composition may be administered to a human at a dosage that results in a serum titer of from about 0.1 μg/ml to about 450 μg /ml and in some embodiments at least 0.1 μg/ml, at least 0.2 μg/ml, at least 0.4 μg/ml, at least 0.5 μg/ml, at least 0 .6 µg/ml, at least 0.8 µg/ml, at least 1 µg/ml, at least 1.5 µg/ml, at least 2 µg/ml, at least 5 µg/ml, at least 10 µg/ml, at least 15 µg/ml, at least 20 µg/ml, at least 25 µg/ml, at least 30 µg/ml, at least 35 µg/ml, at least at least 40 µg/ml, at least 50 µg/ml, at least 75 µg/ml, at least 100 µg/ml, at least 125 µg/ml, at least 150 µg/ml, at least 200 µg/ml, at least 250 µg/ml, at least 300 µg/ml, at least 350 µg/ml, at least 400 µg/ml, at least 450 µg/ml. In addition, the results of in vitro assays may be helpful in facilitating the identification of optimal dosage ranges. The exact dosage used in the composition will also depend on the route of administration and the severity of the C10orf54-mediated disease, and its selection should be made in accordance with the judgment of the practitioner and the condition of each patient.

Effective dose values can be determined by extrapolation using a dose-response curve obtained from in vitro test systems or animal models.

For the antibodies provided herein, the dosage administered to the patient in certain embodiments may range from 0.1 mg/kg to 100 mg/kg of the patient's body weight. In some embodiments, the dosage administered to the patient is from about 1 mg/kg to about 75 mg/kg of the patient's body weight. In certain embodiments, the dosage administered to the patient is from 1 mg/kg to 20 mg/kg of the patient's body weight, for example, from 1 mg/kg to 5 mg/kg of the patient's body weight. In general, human antibodies have a longer half-life in the human body than antibodies from other species due to the presence of an immune response to foreign polypeptides. For this reason, it is often possible to use lower dosages of human antibodies and less frequent administration. In addition, the dosage and frequency of administration of the antibodies proposed in this application can be reduced due to increased absorption and penetration of antibodies into tissues due to modifications, such as lipidation.

In one embodiment, the antibody provided herein is administered 5 times, 4 times, 3 times, 2 times, or 1 time at a dose of about 100 mg/kg or less, about 75 mg/kg or less, about 50 mg/kg, or less, about 25 mg/kg or less, about 10 mg/kg or less, about 5 mg/kg or less, about 1 mg/kg or less, about 0.5 mg/kg or less, or about 0.1 mg/kg kg or less for the prevention, treatment or alleviation of one or more symptoms of a C10orf54-mediated disease. In some embodiments, the antibody provided herein is administered approximately 1-12 times, and these doses can be administered as needed, for example, once a week, once every two weeks, once a month, once every two months, once once every three months, etc., as determined by the doctor. In some embodiments, a lower dose (eg, 1-15 mg/kg) may be administered more frequently (eg, 3-6 times). In other embodiments, a higher dose (eg, 25-100 mg/kg) may be administered less frequently (eg, 1-3 times). However, as will be apparent to those skilled in the art, other dosage amounts and administration schedules are readily ascertainable and are included within the scope of this specification.

In a specific embodiment, the antibody provided herein in a sustained release composition is administered to a subject, such as a human, at a dose of about 100 mg/kg, about 75 mg/kg or less, about 50 mg/kg or less, about 25 mg /kg or less, about 10 mg/kg or less, about 5 mg/kg or less, about 1 mg/kg or less, about 0.5 mg/kg or less, about 0.1 mg/kg or less for warning , treating and/or alleviating one or more symptoms of a C10orf54-mediated disease. In another specific embodiment, the antibody provided herein is administered to a subject, such as a human, not in a sustained release formulation, but rather as a bolus of about 100 mg/kg, about 75 mg/kg or less, about 50 mg/kg. kg or less, about 25 mg/kg or less, about 10 mg/kg or less, about 5 mg/kg or less, about 1 mg/kg or less, about 0.5 mg/kg or less, or about 0.1 mg/kg or less, to prevent, treat, and/or alleviate one or more than one symptom of a C10orf54-mediated disease, and over a period of time, the subject is administered (eg, intranasally or intramuscularly) one, two, three, or four times the antibody provided in this application, in a sustained release composition at a dose of about 100 mg/kg, about 75 mg/kg or less, about 50 mg/kg or less, about 25 mg/kg or less, about 10 mg/kg or less, about 5 mg/kg or less, about 1 mg/kg or less, about 0.5 mg/kg or less, or about 5 mg/kg or less. According to this, "a certain period of time" can be from 1 to 5 days, a week, two weeks or a month.

In some embodiments, a single dose of an antibody provided herein is administered to a patient to prevent, treat, and/or alleviate one or more than one symptom of C10orf54-mediated disease two, three, four, five, six, seven, eight, nine, ten, eleven, twelve times, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty-one, twenty-two, twenty-three, twenty-four, twenty-five, or twenty-six times every two weeks (e.g., approximately 14 days) during the annual course of treatment, and this dose is selected from the group consisting of doses of about 0.1 mg/kg, about 0.5 mg/kg, about 1 mg/kg, about 5 mg/kg, about 10 mg /kg, approximately 15 mg/kg, approximately 20 mg/kg, approximately 25 mg/kg, approximately 30 mg/kg, approximately 35 mg/kg, approximately 40 mg/kg, approximately 45 mg/kg, approximately 50 mg/kg , approximately 55 mg/kg, approximately 60 mg/kg, approximately 65 mg/kg, approximately 70 mg/kg, approximately 75 mg/kg, approximately 80 mg/kg, approximately 85 mg/kg, approximately 90 mg/kg, approximately 95 mg/kg, about 100 mg/kg, or combinations thereof (eg, each once-monthly dose may or may not be the same).

In another embodiment, a single dose of an antibody provided herein is administered to a patient to prevent, treat, and/or alleviate one or more than one symptom of a C10orf54-mediated disease two, three, four, five, six, seven, eight, nine, ten, eleven or twelve times at a frequency of approximately once a month (for example, approximately 30 days) during the annual course of treatment, and this dose is selected from the group consisting of doses of about 0.1 mg/kg, about 0.5 mg/kg, about 1 mg/kg, about 5 mg/kg, about 10 mg/kg, about 15 mg/kg, about 20 mg/kg, about 25 mg/kg, about 30 mg/kg, about 35 mg/kg, about 40 mg/kg, approximately 45 mg/kg, approximately 50 mg/kg, approximately 55 mg/kg, approximately 60 mg/kg, approximately 65 mg/kg, approximately 70 mg/kg, approximately 75 mg/kg, approximately 80 mg/ kg, about 85 mg/kg, about 90 mg/kg, about 95 mg/kg, about 100 mg/kg, or combinations thereof (eg, each monthly dose may or may not be the same).

In one embodiment, a single dose of an antibody provided herein is administered to a patient to treat, prevent, and/or alleviate one or more symptoms of a C10orf54-mediated disease two, three, four, five, or six times at a frequency of approximately once every two months (for example, approximately 60 days) during an annual course of treatment, and this dose is selected from the group consisting of doses of about 0.1 mg/kg, about 0.5 mg/kg, about 1 mg/kg, about 5 mg/ kg, approximately 10 mg/kg, approximately 15 mg/kg, approximately 20 mg/kg, approximately 25 mg/kg, approximately 30 mg/kg, approximately 35 mg/kg, approximately 40 mg/kg, approximately 45 mg/kg, about 50 mg/kg, about 55 mg/kg, about 60 mg/kg, about 65 mg/kg, about 70 mg/kg, about 75 mg/kg, about 80 mg/kg, about 85 mg/kg, about 90 mg/kg, about 95 mg/kg, about 100 mg/kg, or combinations thereof (eg, each bimonthly dose may or may not be the same).

In some embodiments, a single dose of an antibody provided herein is administered to a patient to treat, prevent, and/or alleviate one or more symptoms of a C10orf54-mediated disease two, three, or four times at a frequency of approximately once every three months (e.g., approximately 120 days) during the annual course of treatment, and this dose is selected from the group consisting of doses of about 0.1 mg/kg, about 0.5 mg/kg, about 1 mg/kg, about 5 mg/kg, about 10 mg /kg, approximately 15 mg/kg, approximately 20 mg/kg, approximately 25 mg/kg, approximately 30 mg/kg, approximately 35 mg/kg, approximately 40 mg/kg, approximately 45 mg/kg, approximately 50 mg/kg , approximately 55 mg/kg, approximately 60 mg/kg, approximately 65 mg/kg, approximately 70 mg/kg, approximately 75 mg/kg, approximately 80 mg/kg, approximately 85 mg/kg, approximately 90 mg/kg, approximately 95 mg/kg, about 100 mg/kg, or combinations thereof (eg, each trimonthly dose may or may not be the same).

In certain embodiments, the route of administration to a patient of a dose of an antibody provided herein is intranasal, intramuscular, intravenous, or a combination thereof, but other routes described herein are also acceptable. Each dose may be administered using the same or different routes of administration. In some embodiments, an antibody provided herein can be administered using different routes of administration concurrently with or after other doses of the same or another antibody provided herein.

In some embodiments, the antibodies provided herein are administered to a subject for prophylactic or therapeutic purposes. Antibodies can be administered to a subject for prophylactic or therapeutic purposes in order to prevent, attenuate or alleviate a C10orf54-mediated disease or symptoms thereof.

DIAGNOSTIC USE OF ANTIBODIES

The labeled antibodies provided herein and their derivatives and analogs that bind to the C10orf54 antigen can be used for diagnostic purposes to detect, diagnose, or monitor C10orf54-mediated disease. In addition, this application provides methods for detecting C10orf54-mediated disease, including: (a) analyzing the expression of a C10orf54 antigen in cells or a tissue sample of a subject using one or more antibodies provided in this application that bind to the C10orf54 antigen; and (b) comparing levels of C10orf54 antigen with a control level, such as levels in normal tissue samples (eg, from a patient without C10orf54-mediated disease or from the same patient before the onset of disease), wherein the level of C10orf54 antigen analyzed increases compared with reference levels of C10orf54 antigen indicates the presence of C10orf54-mediated disease.

Also provided by the present invention is a diagnostic assay for diagnosing a C10orf54-mediated disease, comprising: (a) testing the level of a C10orf54 antigen in cells or a tissue sample of an individual using one or more antibodies provided herein that bind to the C10orf54 antigen; and (b) comparing the level of C10orf54 antigen with a control level, such as levels in normal tissue samples, wherein an increase in the analyzed level of C10orf54 antigen compared with a control level of C10orf54 antigen indicates the presence of a C10orf54-mediated disease. More complete diagnosis of C10orf54-mediated disease may allow health care providers to implement preventive measures or intensive treatment earlier, thereby preventing the development or further progression of C10orf54-mediated disease.

The antibodies provided herein can be used to analyze levels of C10orf54 antigen in a biological sample using classical immunohistological methods as set forth herein or as are known to those skilled in the art (for example, see Jalkanen et al., 1985, J. Cell Biol., 101: 976-985; and Jalkanen et al., 1987, J. Cell. Biol., 105: 3087-3096). Other antibody methods useful for detecting gene expression include immunoassays such as enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA). Suitable labels for antibody assays are known in the art and include enzymatic labels such as glucose oxidase; radioactive isotopes such as iodine ( ¹²⁵ I, ¹²¹ I), carbon ( ¹⁴ C), sulfur ( ³⁵ S), tritium ( ³ H), indium ( ¹²¹ In) and technetium ( ⁹⁹ Tc); luminescent tags such as luminol; and fluorescent labels such as fluorescein, rhodamine and biotin.

According to one aspect of the present invention, there is provided a method for detecting and diagnosing C10orf54-mediated disease in humans. In one embodiment, the diagnosis includes: a) administering (eg, parenterally, subcutaneously, or intraperitoneally) to a subject an effective amount of a labeled antibody that binds to the C10orf54 antigen; b) waiting for a period of time after administration to allow the labeled antibody to concentrate in the subject predominantly at sites of expression of the C10orf54 antigen (and to allow unbound labeled molecules to reach background levels); c) determining the background level; and d) detecting the labeled antibody in the subject, wherein detection of the labeled antibody above background levels indicates that the subject has a C10orf54-mediated disease. The background level can be determined by various methods, including comparing the number of detected labeled molecules with a standard value previously determined for that particular system.

It will be appreciated in the art that the size of the subject and the imaging system used will determine the amount of imaging array required to obtain a diagnostic image. For a human subject, in the case of a radioactive isotope group, the amount of radioactive compound administered will typically range from about 5 to 20 millicuries for ⁹⁹ Tc. The labeled antibody will then preferentially accumulate at the site of cells that contain the particular protein. In vivo tumor imaging is described in SW Burchiel et al., “Immunopharmacokinetics of Radiolabeled Antibodies and Their Fragments.” (Chapter 13 in Tumor Imaging: The Radiochemical Detection of Cancer, S. W. Burchiel and B. A. Rhodes, eds., Masson Publishing Inc. (1982)).

Depending on several factors, including the type of label used and the route of administration, the amount of time after administration to allow the labeled antibody to concentrate primarily at sites of antigen expression in the subject and for unbound labeled antibody to reach background levels ranges from 6 to 48 hours, or from 6 to 24 hours, or from 6 to 12 hours. In another embodiment, the period of time after administration is from 5 to 20 days or from 5 to 10 days.

In one embodiment, monitoring of the C10orf54-mediated disease is performed by repeating the method of diagnosing the C10orf54-mediated disease, for example, one month after the initial diagnosis, six months after the initial diagnosis, one year after the initial diagnosis, etc.

The presence of a labeled molecule can be detected in a subject using methods known in the art for in vivo scanning. These methods depend on the type of label being used. Those skilled in the art will be able to determine an appropriate method for detecting a particular label. Methods and devices that may be used in the diagnostic methods proposed herein include, but are not limited to, computed tomography (CT), whole body scans such as positron emission tomography (PET), magnetic resonance imaging (MRI) and echography.

In a specific embodiment, the molecule is labeled with a radioactive isotope and detected in a patient using a radiation sensitive surgical instrument (Thurston et al., US Pat. No. 5,441,050). In another embodiment, the molecule is labeled with a fluorescent compound and detected in the patient using a fluorescence-sensitive scanning device. In another embodiment, the molecule is labeled with a positron-emitting metal and detected in the patient using positron emission tomography. In yet another embodiment, the molecule is labeled with a paramagnetic label and detected in a patient using magnetic resonance imaging (MRI).

METHODS OF OBTAINING ANTIBODIES

The antibodies provided herein that bind to an antigen can be produced by any method known in the art for antibody synthesis, particularly using chemical synthesis or recombinant expression methods. In the practical application of this description, unless otherwise indicated, traditional methods of molecular biology, microbiology, genetic analysis, recombinant DNA, organic chemistry, biochemistry, PCR, synthesis and modification of oligonucleotides, nucleic acid hybridization and methods of related fields that are within the competence of a specialist are used. in this field of technology. These methods are described in the references cited herein and are fully disclosed in the literature. See, for example, Maniatis et al. (1982) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press; Sambrook et al. (1989), Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor Laboratory Press; Sambrook et al. (2001) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; Ausubel et al., Current Protocols in Molecular Biology, John Wiley & Sons (1987 and annual revisions); Current Protocols in Immunology, John Wiley & Sons (1987 and annual revisions); Gait (ed.) (1984) Oligonucleotide Synthesis: A Practical Approach, IRL Press; Eckstein (ed.) (1991) Oligonucleotides and Analogues: A Practical Approach, IRL Press; Birren et al, (eds.) (1999) Genome Analysis: A Laboratory Manual, Cold Spring Harbor Laboratory Press.

Polyclonal antibodies that bind to antigen can be produced using various techniques well known in the art. For example, a human antigen can be administered to a variety of animal hosts, including, but not limited to, rabbits, mice, rats, etc., to induce sera containing polyclonal antibodies specific for the human antigen. Various adjuvants can be used to enhance the immune response, depending on the host species, and these include, but are not limited to, Freund's adjuvant (complete and incomplete), mineral gels such as aluminum hydroxide gel, surfactants such as lysolecithin , Pluronic-type polyols, polyanions, peptides, oil emulsions, keyhole limpet hemocyanins, dinitrophenol, and potentially beneficial human adjuvants such as BCG (Bacillus Calmette-Guerin) and Corynebacterium parvum. Such adjuvants are also well known in the art.

Monoclonal antibodies can be produced using a wide range of methods known in the art, including the use of hybridoma and recombinant technologies and phage display methods, or combinations thereof. For example, monoclonal antibodies can be produced using hybridoma techniques, including those known in the art as reported in, for example, Harlow et al., Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory Press, 2nd ed. 1988); Hammerling et al., Monoclonal Antibodies and T-Cell Hvbridomas 563-681 (Elsevier, N.Y., 1981), incorporated by reference in its entirety. The term "monoclonal antibody" as used herein is not limited to antibodies produced using hybridoma technology. Other typical methods for producing monoclonal antibodies are discussed elsewhere in this specification, such as, for example, the use of KM mouse™ technology. Additional typical methods for producing monoclonal antibodies are provided in the examples herein.

Methods for producing and screening specific antibodies using hybridoma technology are generally accepted and well known in the art. Briefly, mice can be immunized with the C10orf54 antigen, and once an immune response is detected, for example, antibodies specific to the C10orf54 antigen are detected in the mouse serum, mouse spleens are harvested and splenocytes are isolated. Splenocyte fusion is then performed using well known methods with any suitable myeloma cells, for example cells of the SP20 cell line, which can be obtained from ATCC (American Type Culture Collection). Hybridomas are selected and cloned using the limiting dilution method.

Additionally, the repeat immunization multiple site (RIMMS) method can be used to immunize an animal (Kilptrack et al., 1997, Hybridoma, 16:381-9, incorporated by reference in its entirety). The hybridoma clones are then analyzed by methods known in the art for cells that secrete antibodies capable of binding to the polypeptide in question. Immunization of mice with positive hybridoma clones produces ascites fluid, which typically contains high levels of antibodies.

Accordingly, this application also provides methods for producing antibodies by culturing a hybridoma cell secreting a modified antibody provided herein, wherein in certain embodiments the hybridoma is obtained by fusing splenocytes isolated from a mouse immunized with the C10orf54 antigen with myeloma cells and then screening hybridomas resulting from this fusion, with respect to hybridoma clones that secrete an antibody capable of binding to the C10orf54 antigen.

Antibody fragments recognizing specific C10orf54 antigens can be prepared by any method known to those skilled in the art. For example, the Fab and F(ab') ₂ fragments proposed in this application can be obtained by proteolytic cleavage of immunoglobulin molecules using enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab') ₂ fragments). F(ab') ₂ fragments contain a variable region, a light chain constant region and a heavy chain CH1 domain. In addition, the antibodies proposed in this application can also be obtained using various phage display methods known in the art.

For example, antibodies can also be produced using various phage display methods. In phage display methods, the functional domains of antibodies are displayed on the surface of phage particles that carry the polynucleotide sequences encoding them. In particular, DNA sequences encoding the VH and VL domains are amplified from animal cDNA libraries (eg, human or mouse diseased tissue cDNA libraries). The DNA encoding the VH and VL domains is recombined with the scFv linker using PCR and cloned into the phagemid vector. The vector is introduced using electroporation into E. coli and E. coli is infected with helper phage. The phage used in these methods is usually a filamentous bacteriophage, including fd and M13, and the nucleotide sequences of the VH and VL domains are usually fused recombinantly to either phage gene III or gene VIII. A phage expressing an antigen-binding domain that binds to a particular antigen can be selected or identified using the antigen, for example, using a labeled antigen or an antigen bound to or captured on a solid surface or bead. Examples of phage display methods that can be used to produce the antibodies proposed herein include those described in Brinkman et al., 1995, J. Immunol. Methods, 182: 41-50; Ames et al., 1995, J. Immunol. Methods, 184: 177-186; Kettleborough et al., 1994, Eur. J Immunol 24: 952–958; Persic et al., 1997, Gene, 187: 9-18; Burton et al., 1994, Advances in Immunology, 57: 191-280; in PCT application No. PCT/GB91/01 134; international publications Nos. WO 90/02809, WO 91/10737, WO 92/01047, WO 92/18619, WO 93/1 1236, WO 95/15982, WO 95/20401 and WO97/13844; and US patents No. 5698426, 5223409, 5403484, 5580717, 5427908, 5750753, 5821047, 5571698, 5427908, 5516637, 5780225, 5658727, 5733743 and 5969108; each of which is incorporated herein by reference in its entirety.

As described in the above references, following selection using a phage, antibody-encoding portions of the phage DNA can be isolated and used to produce whole antibodies, including human antibodies, or any other desired antigen-binding fragment, and expressed in any desired host , including mammalian cells, insect cells, plant cells, yeast and bacteria, for example, as described below. Methods for producing Fab, Fab' and F(ab') ₂ fragments recombinantly can also be applied using methods known in the art, such as those described in PCT publication No. WO 92/22324; Mullinax et al., 1992, Bio Techniques, 12(6): 864-869; Sawai et al., 1995, AJRI, 34: 26-34; and Better et al., 1988, Science, 240: 1041-1043 (these sources are incorporated by reference in their entirety).

To generate whole antibodies, PCR primers containing VH or VL nucleotide sequences, a restriction site, and flanking sequences to protect the restriction site can be used to amplify VH or VL sequences in scFv clones. Using cloning techniques known to those skilled in the art, PCR-amplified VH domains can be cloned into vectors expressing a VH constant region, for example, human immunoglobulin gamma 4 constant region, and PCR-amplified VL domains can be cloned into vectors , expressing a VL constant region, for example, human immunoglobulin kappa or lambda constant regions. The VH and VL domains can also be cloned into a single vector expressing the required constant regions. The heavy chain introducing vectors and the light chain introducing vectors are then co-transfected into cell lines to produce stably or transiently transfected cell lines that express full-length antibodies, eg IgG, using methods known to those skilled in the art.

For some applications, including in vivo use of antibodies in humans and in vitro detection assays, human or chimeric antibodies can be used. Fully human antibodies are particularly desirable for the therapeutic treatment of humans. Human antibodies can be produced by a variety of methods known in the art, including the phage display methods described above using antibody libraries derived from human immunoglobulin sequences. Also see US Patent Nos. 4,444,887 and 4,716,111 and International Application Publications Nos. WO 98/46645, WO 98/50433, WO 98/24893, WO 98/16654, WO 96/34096, WO 96/33735 and WO 91/10741 ; all of which are incorporated herein by reference in their entirety.

In specific embodiments, human antibodies are produced. Human antibodies and/or fully human antibodies can be prepared using any method known in the art, including the examples provided herein. For example, using transgenic mice that are unable to express functional endogenous immunoglobulins, but which can express human immunoglobulin genes. For example, human immunoglobulin heavy and light chain gene complexes can be introduced randomly or using homologous recombination into mouse embryonic stem cells. Alternatively, nucleotide sequences encoding the variable region, constant region and D-segment (diversity region) of human immunoglobulin can be introduced into mouse embryonic stem cells in addition to the human immunoglobulin heavy and light chain genes. The mouse immunoglobulin heavy and light chain genes can be rendered nonfunctional individually or together with the introduction of the human immunoglobulin locus by homologous recombination. In particular, homozygous deletion of the J _H region prevents the formation of endogenous antibodies. Modified embryonic stem cells are grown and microinjected into blastocytes to produce chimeric mice. Chimeric mice are further bred to produce homozygous offspring that express human antibodies. Transgenic mice are immunized in the usual manner with a selected antigen, for example the whole polypeptide or part of a polypeptide. Monoclonal antibodies directed against a given antigen can be generated from immunized, transgenic mice using traditional hybridoma technology. Transgenic human immunoglobulins contained in transgenic mice undergo rearrangement during B cell differentiation and subsequently undergo class switching and somatic mutations. Thus, therapeutically useful IgG, IgA, IgM and IgE antibodies can be produced using this method. For a review of this technology for producing human antibodies, see Lonberg and Huszar (1995, Int. Rev. Immunol., 13: 65-93). For a detailed discussion of this technology for the production of human antibodies and human monoclonal antibodies and protocols for the production of such antibodies, see, for example, PCT Publication Nos. WO 98/24893, WO 96/34096 and WO 96/33735; and US Pat. Nos. 5,413,923, 5,625,126, 5,633,425, 5,569,825, 5,661,016, 5,545,806, 5,814,318, and 5,939,598, which are incorporated herein by reference in their entirety. Other methods are described in detail in the examples herein. In addition, companies such as Abgenix, Inc. can be contacted to obtain human antibodies directed to a selected antigen using technology similar to that described above. (Freemont, CA) and Genpharm (San Jose, CA).

A chimeric antibody is a molecule in which different parts of the antibody are derived from different immunoglobulin molecules. Methods for producing chimeric antibodies are known in the art. See, for example, Morrison, 1985, Science, 229: 1202; Oi et al., 1986, BioTechniques, 4: 214; Gillies et al., 1989, J. Immunol. Methods, 125: 191-202 and US Patent Nos. 5807715, 4816567, 4816397 and 6331415, which are incorporated herein by reference in their entirety.

A humanized antibody is an antibody or variant thereof or fragment thereof that is capable of binding to a specific antigen and that contains a framework region having essentially the amino acid sequence of a human immunoglobulin and a CDR having essentially the amino acid sequence of an immunoglobulin non-human species. A humanized antibody contains essentially at least one domain, and typically all of both variable domains (Fab, Fab', F(ab') ₂ , Fabc, Fv), in which all or substantially all of the CDR regions correspond to those of the immunoglobulin species, non-human (eg, donor antibody), and all or substantially all of the framework regions are the same as the human immunoglobulin consensus sequence. In certain embodiments, the humanized antibody also contains at least a portion of an immunoglobulin constant region (Fc), typically human immunoglobulin. Typically, an antibody will contain both a light chain and at least a heavy chain variable domain. The antibody may also include a CH1 region, a hinge region, CH2, CH3 and CH4 regions of the heavy chain. The humanized antibody may be selected from any class of immunoglobulins, including IgM, IgG, IgD, IgA and IgE, and any isotype, including IgG1, IgG2, IgG3 and IgG4. Typically, the constant domain is a complement fixation constant domain when it is desired that the humanized antibody exhibit cytotoxic activity, and this class is typically IgG1. When such cytotoxic activity is undesirable, the constant domain may be of the IgG2 class. Examples of VL and VH constant domains that may be used in certain embodiments include, but are not limited to, C-kappa and C-gamma-1 (nG1m) described in Johnson et al, (1997), J. Infect. Dis., 176, 1215-1224 and described in US patent No. 5824307. A humanized antibody may contain sequences from more than one class or isotype, and the selection of specific constant domains to optimize desired effector functions is within the skill of ordinary skill in the art. The framework and CDR regions of a humanized antibody do not necessarily correspond exactly to the original sequences; for example, the donor CDR or consensus framework may be subject to mutations with the substitution, insertion, or deletion of at least one residue such that a given CDR or framework residue at that site does not correspond to either consensus nor the administered antibody. Such mutations, however, will not be extensive. Typically, at least 75% of the residues of the humanized antibody will match the residues of the original FR and CDR sequences, more commonly 90% or greater than 95%. Humanized antibodies can be produced using various methods known in the art, including, but not limited to, CDR grafting (European Patent No. EP 239400; International Publication No. WO 91/09967; and US Patent Nos. 5225539, 5530101 and 5585089), veining or surface modification (European patent nos. EP 592106 and EP 519596; Padlan, 1991, Molecular Immunology, 28(4/5): 489-498; Studnicka et al., 1994, Protein Engineering, 7(6) : 805-814; and Roguska et al., 1994, PNAS, 91: 969-973), chain shuffling (US Patent No. 5565332) and methods described, for example, in US Patent No. 6407213, US Patent No. 5766886, WO 9317105 , Tan et al., J. Immunol., 169: 1119 25 (2002), Caldas et al., Protein Eng., 13(5): 353-60 (2000), Morea et al., Methods, 20(3 ): 267-79 (2000), Baca et al., J. Biol. Chem., 272(16): 10678-84 (1997), Roguska et al., Protein Eng., 9(10): 895 904 (1996), Couto et al., Cancer Res., 55 (23 Supp): 5973s-5977s (1995), Couto et al., Cancer Res., 55(8): 1717-22 (1995), Sandhu JS, Gene, 150(2): 409-10 (1994) and Pedersen et al., J. Mol. Biol., 235(3): 959-73 (1994). Also see US Patent Application Publication No. US 2005/0042664 A1 (February 24, 2005), which is incorporated herein by reference in its entirety. Often, framework residues in framework regions will be replaced by the corresponding residue from the CDR of the donor antibody in order to alter (eg, improve) binding to the antigen. Such scaffold substitutions are identified by methods well known in the art, for example, by modeling the interaction of CDR residues and the scaffold to identify scaffold residues important for antigen binding, and by sequence comparison to identify unusual scaffold residues at specific positions. (See, for example, Queen et al., US Pat. No. 5,585,089; and Reichmann et al., 1988, Nature, 332:323, which are incorporated herein by reference in their entirety).

Single domain antibodies, for example, antibodies that do not contain light chains, can be produced by methods well known in the art. See Riechmann et al., 1999, J. Immunol., 231: 25-38; Nuttall et al., 2000, Curr. Pharm. Biotechnol., 1(3): 253-263; Muylderman, 2001, J. Biotechnol., 74(4): 277302; US Patent No. 6005079; and International Publication Nos. WO 94/04678, WO 94/25591 and WO 01/44301, each of which is incorporated herein by reference in its entirety.

In addition, antibodies that bind to the C10orf54 antigen can in turn be used to generate anti-idiotypic antibodies that “mock” the antigen using methods well known to those skilled in the art. (See, for example, Greenspan & Bona, 1989, FAS EB J., 7(5): 437-444; and Nissinoff, 1991, J. Immunol., 147(8): 2429-2438).

POLYNUCLEOTIDES ENCODING ANTIBODY

In addition, this application provides polynucleotides containing a nucleotide sequence encoding an antibody provided herein that binds to C10orf54 (eg, a C10orf54 polypeptide, a fragment of a C10orf54 polypeptide, a C10orf54 epitope). In addition, this application provides polynucleotides that hybridize under conditions of high stringency, intermediate or low stringency, for example, as defined above, with polynucleotides that encode the antibody or modified antibody proposed in this application.

In certain embodiments, the nucleic acid molecules provided herein contain or consist of a nucleic acid sequence encoding the VH and/or VL amino acid sequence described herein, or any combination thereof (for example, such as a nucleotide sequence encoding an antibody provided herein, e.g., a full-length antibody, a heavy and/or light chain antibody, or a single chain antibody provided herein).

RECOMBINANT ANTIBODY EXPRESSION

Recombinant expression of an antibody provided herein (e.g., a full-length antibody, a heavy and/or light chain antibody, or a single chain antibody provided herein) that binds the C10orf54 antigen requires the construction of an expression vector containing a polynucleotide that encodes the antibody. Once a polynucleotide encoding an antibody molecule, an antibody heavy or light chain, or a fragment thereof (such as a fragment containing a heavy and/or light chain variable domain) has been produced, a vector for producing the antibody molecule can be produced using recombinant technology techniques. DNA, well known in the art. Thus, methods for producing a protein by expressing a polynucleotide containing a nucleotide sequence encoding an antibody are described herein. To construct expression vectors containing antibody coding sequences and corresponding transcriptional and translational control signals, methods that are well known to those skilled in the art can be used. These methods include, for example, in vitro recombinant DNA methods, synthetic methods, and in vivo genetic recombination. Thus, this application also provides replication-competent vectors containing a nucleotide sequence encoding an antibody molecule of the present application, an antibody heavy or light chain, an antibody heavy or light chain variable domain or fragment thereof, or a heavy or light chain CDR, and all of them are operably linked to the promoter. Such vectors may include a nucleotide sequence encoding the constant region of an antibody molecule (see, for example, International Publications Nos. WO 86/05807 and WO 89/01036; and US Pat. No. 5,122,464), and the nucleotide sequence of the antibody variable domain may be cloned into such a vector for expressing the entire heavy chain, the entire light chain, or both the entire heavy and light chains.

The expression vector is transferred into a host cell by conventional methods, and the transfected cells are then cultured by conventional methods to produce the antibody provided herein. Thus, this application also provides host cells containing a polynucleotide encoding an antibody provided herein, or fragments thereof, or a heavy or light chain or fragment thereof, or a single chain antibody provided herein, all of which are operably linked with a heterologous promoter. In certain embodiments for the expression of double-chain antibodies, vectors encoding both the heavy and light chains can be co-expressed in a host cell to express the entire immunoglobulin molecule, as described in detail below.

To express the antibodies proposed in this application, you can use a variety of vector systems for expression in host cells (see, for example, US patent No. 5807715). Such host cell expression systems provide vehicles by which coding sequences of interest can be obtained and subsequently purified, but also represent cells that, after transformation or transfection with the appropriate nucleotide coding sequences, can express in situ the antibody provided herein . These include, but are not limited to, microorganisms such as bacteria (eg, E. coli and B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA, or cosmid DNA expression vectors containing antibody coding sequences; yeast (eg, Saccharomyces pichia) transformed with recombinant yeast expression vectors containing antibody coding sequences; insect cell systems infected with recombinant viral expression vectors (eg, baculovirus-based) containing antibody coding sequences; plant cell systems infected with recombinant viral expression vectors (eg, cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transfected with recombinant plasmid expression vectors (eg, Ti plasmid) containing antibody coding sequences; or mammalian cell systems (eg, COS cells, Chinese hamster ovary (CHO), newborn Syrian hamster kidney (BHK), HEK293 (human embryonic kidney line 293), NS0 and 3T3) carrying recombinant expression constructs containing promoters derived from genome of mammalian cells (eg, metallothionein promoter) or from mammalian viruses (eg, adenovirus late promoter; vaccinia virus 7.5K protein promoter). In certain embodiments, bacterial cells, such as Escherichia coli, or eukaryotic cells, especially used to express the entire recombinant antibody molecule, are used to express the recombinant antibody molecule. For example, mammalian cells, such as Chinese hamster ovary (CHO) cells, together with a vector, such as a vector containing the major immediate early gene promoter element from human cytomegalovirus, are an effective system for antibody expression (Foecking et al., 1986, Gene, 45: 101; and Cockett et al., 1990, Bio/Technology, 8: 2). In specific embodiments, the antibodies provided herein are produced in CHO cells. In a specific embodiment, the expression of nucleotide sequences encoding antibodies provided herein that bind to the C10orf54 antigen is regulated by a constitutive promoter, an inducible promoter, or a tissue-specific promoter.

In bacterial systems, depending on the intended use of the antibody molecule to be expressed, a number of expression vectors may be preferably selected. For example, when large quantities of the antibody must be produced to create pharmaceutical compositions based on an antibody molecule, it may be desirable to use vectors that drive expression to produce high levels of fusion protein products that are easy to purify. Such vectors include, but are not limited to, the E. coli expression vector pUR278 (Ruther et al., 1983, EMBO, 12:1791), in which the antibody coding sequence can be ligated individually into the vector in frame with the lac Z coding region , resulting in a fusion protein; pIN vectors (Inouye & Inouye, 1985, Nucleic Acids Res., 13: 3101-3109; Van Heeke & Schuster, 1989, J. Biol. Chem., 24: 5503-5509) and the like. pGEX vectors can also be used to express foreign polypeptides as glutathione 5-transferase (GST) fused proteins. In general, such fusion proteins are soluble and can be easily purified from lysed cells by adsorption and binding to glutathione agarose matrix beads followed by elution in the presence of free glutathione. pGEX vectors are designed to include protease cleavage sites such as thrombin or factor Xa so that the cloned target gene product can be freed from GST moiety.

In insect (cell) systems, Autographs californica nuclear polyhedrosis virus (AcNPV) is used as a vector for the expression of foreign genes. This virus develops in Spodoptera frugiperda cells. The antibody coding sequence can be cloned individually into non-essential regions (eg, the polyhedrin gene) of the virus and placed under the control of an AcNPV promoter (eg, the polyhedrin gene promoter).

In host cells in the case of mammals, a number of virus-based expression systems can be used. In cases where an adenovirus is used as an expression vector, the sequence encoding the antibody of interest can be ligated to the sequence of the adenovirus transcription/translation control complex, for example, containing a late promoter and a tripartite leader sequence. This chimeric gene can then be inserted into the adenovirus genome via in vitro or in vivo recombination. Insertion into a non-essential region of the viral genome (eg, the E1 or E3 region) will result in a recombinant viable virus capable of expressing the antibody molecule in infected hosts (eg, see Logan & Shenk, 1984, Proc. Natl. Acad. Sci. USA , 81: 355-359). Specific initiation signals may also be required to achieve efficient translation of integrated antibody coding sequences. Such signals include the ATG start codon and adjacent sequences. In addition, the start codon must be in the reading frame corresponding to the desired coding sequence to ensure translation of the entire insert. These exogenous translation control signals and start codons can be of various origins, both natural and synthetic. The efficiency of expression can be increased by introducing appropriate transcription enhancing elements, transcription terminators, etc. (See, for example, Bittner et al., 1987, Methods in Enzymol., 153: 51-544).

In addition, a host cell strain can be selected that modulates the expression of the inserted sequences or modifies and processes the gene product in a particular desired manner. Such modifications (eg, glycosylation) and processing (eg, cleavage) of protein products may be important for the function of a given protein. Different host cells have characteristic and specific mechanisms for post-translational processing and modification of proteins and gene products. Appropriate cell lines or host systems can be selected to ensure correct modification and processing of the foreign protein being expressed. For this purpose, eukaryotic host cells can be used, which have the cellular machinery for proper processing of the primary transcript, glycosylation and phosphorylation of the gene product. Such host cells in the case of mammals include, but are not limited to, CHO, VERY, BHK, HeLa, COS, MDCK, HEK293, 3T3, WI-38, BT483, Hs578T, HTB2, BT20 and T47D, NS0 (mouse myeloma cell line) cells , which does not endogenously produce any immunoglobulin chains), CRL7O3O and HsS78Bst. In specific embodiments, the fully human anti-C10orf54 monoclonal antibodies provided herein are produced in mammalian cells, such as CHO cells.

For long-term production of recombinant proteins in high yield, stable expression is useful, but not required. For example, cell lines can be constructed that stably express a given antibody molecule. Instead of using expression vectors that contain viral origins of replication, host cells can be transfected with DNA controlled by appropriate expression regulatory elements (eg, promoter, enhancer sequences, transcription terminators, polyadenylation sites, etc.) and containing a selectable marker. After introducing foreign DNA, the engineered cells can be left to grow for 1-2 days in an enriched medium, after which they can be transferred to a selective medium. The selectable marker in the recombinant plasmid confers the stability needed for selection, and its presence allows cells to stably integrate the plasmid into their chromosomes and grow into foci, which in turn can be cloned and expanded into cell lines. This method can advantageously be used to construct cell lines that express the antibody molecule. Such engineered cell lines may be useful, in particular, in the screening and evaluation of compounds that directly or indirectly interact with a given antibody molecule.

A number of selection systems can be used, including, but not limited to, the herpes simplex virus thymidine kinase (tk) genes (Wigler et al., 1977, Cell, 11:223), hypoxanthine guanine phosphoribosyltransferase (hgprt) genes (Szybalska & Szybalski, 1992, Proc. Natl Acad. Sci. USA, 48: 202) and adenine phosphoribosyltransferase (aprt) (Lowy et al., 1980, Cell, 22: 8-17), which can be used in tk-, hgprt- or aprt-bearing cells, respectively. . In addition, antimetabolite resistance can be used as a basis for selection in the case of the following genes: dhfr (dihydrofolate reductase gene), which confers resistance to methotrexate (Wigler et al., 1980, Proc. Natl. Acad. Sci. USA, 77: 357 ; O'Hare et al., 1981, Proc. Acad. Sci. USA, 78: 1527); gpt (glutamate-pyruvate transaminase gene), which confers resistance to mycophenolic acid (Mulligan & Berg, 1981, Proc. Natl. Acad. Sci. USA, 78: 2072); neo (neomycin phosphotransferase gene), which confers resistance to aminoglycoside G-418 (Wu and Wu, 1991, Biotherapy, 3: 87-95; Tolstoshev, 1993, Ann. Rev. Pharmacol. Toxicol., 32: 573-596; Mulligan, 1993, Science, 260: 926-932; and Morgan and Anderson, 1993, Ann. Rev. Biochem., 62: 191-217; TIB TECH, 11(5): I55-215; and hygro (hygromycin resistance gene), which confers resistance to hygromycin (Santerre et al., 1984, Gene, 30: 147). Methods generally known in the art of recombinant DNA technology can invariably be used to select the desired recombinant clone, and such methods are described, for example, in Ausubel et al., (eds.), Current Protocols in Molecular Biology, John Wiley & Sons, NY (1993). ; Kriegler, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY (1990); and in chapters 12 and 13 in Dracopoli et al. (eds.), Current Protocols in Human Genetics, John Wiley & Sons, NY (1994); ColberreGarapin et al., 1981, J. Mol. Biol., 150:1, which are incorporated herein by reference in their entirety.

Expression levels of an antibody molecule can be increased using vector amplification (for a review, see Bebbington and Hentschel, The use of vectors based on gene amplification for the expression of cloned genes in mammalian cells in DNA cloning, vol. 3 (Academic Press, New York, 1987)). When a marker in a vector system expressing an antibody is amplified, increasing the level of inhibitor present in the host cell culture will cause an increase in the copy number of the marker gene. Since the amplified region is associated with the gene encoding the antibody, production of the antibody will also be enhanced (Crouse et al., 1983, Mol. Cell. Biol., 3: 257).

A host cell can be co-transfected with two expression vectors provided herein, the first vector encoding a heavy chain polypeptide and the second vector encoding a light chain polypeptide. Both of these vectors may contain identical selectable markers that provide identical expression of the heavy and light chain polypeptides. Alternatively, a single vector may be used that encodes and is capable of expressing both heavy and light chain polypeptides. In such a situation, the light chain nucleotide sequence must be placed before the heavy chain nucleotide sequence in order to avoid the formation of an excess of toxic free heavy chain (Proudfoot, 1986, Nature, 322: 52; and Kohler, 1980, Proc. Natl. Acad. Sci. USA, 77: 2197-2199). The coding sequences for the heavy and light chains may comprise cDNA or genomic DNA.

Once an antibody has been produced using recombinant expression, it can be purified by any method known in the art for purifying an immunoglobulin molecule, for example, chromatography (e.g., ion exchange, affinity, particularly by affinity for a specific antigen after purification using column chromatography on a Protein A-immobilized support and gel filtration), centrifugation, differential solubility, or any other standard protein purification method. In addition, to facilitate purification, the antibodies provided herein can be fused to heterologous polypeptide sequences set forth herein or otherwise known in the art.

SETS

The present invention also provides a pharmaceutical package or pharmaceutical kit comprising one or more containers filled with one or more ingredients of the pharmaceutical compositions provided herein, for example, one or more antibodies provided herein. It is possible that such container(s) may include a statement in a form prescribed by a government agency regulating the manufacture, use, or sale of pharmaceuticals or biological products that reflects that agency's approval for manufacture, use, or sale for human administration. In some embodiments, the kit includes an insert leaflet. As used, the term “package leaflet” refers to instructions typically included in commercial packaging of therapeutic products that contain information regarding the indications, use, dosage, administration, contraindications and/or warnings regarding the use of such therapeutic products, as well as instructions for use.

In addition, this application provides kits that can be used in the methods described above. In one embodiment, the kit contains an antibody provided herein, such as an isolated antibody, in one or more containers. In a specific embodiment, the kits provided herein contain substantially isolated C10orf54 antigen as a control. In certain embodiments, the kits provided herein further comprise a control antibody that does not react with the C10orf54 antigen. In another specific embodiment, the kits provided herein contain a means for detecting binding of the modified antibody to the C10orf54 antigen (for example, the antibody may be conjugated to a detectable substrate, such as a fluorescent compound, an enzymatic substrate, a radioactive compound, or a luminescent compound, or to a detectable substrate a second antibody may be conjugated that recognizes the first antibody). In specific embodiments, the kit may include a recombinantly produced or chemically synthesized C10orf54 antigen. The C10orf54 antigen provided in such a kit can also be attached to a solid support. In a more specific embodiment, the detection means of the kit described above includes a solid support to which the C10orf54 antigen is attached. Such a kit may also include an unattached reporter-labeled anti-human antibody. In this embodiment, detection of antibody binding to the C10orf54 antigen can be determined by binding to a reporter-labeled antibody.

The following examples are offered by way of illustration and without limitation.

EXAMPLES

EXAMPLE 1. IDENTIFICATION OF C10ORF54 ON THE SURFACE OF TUMOR CELLS IN ACUTE MYELOGENIC LEUKEMIA (AML)

A total of 14 fresh bone marrow mononuclear cell (BMMC) samples from patients with AML were obtained from AllCells, and an additional 16 frozen samples were from patients from the Fred Hutchinson Cancer Research Center (FHCRC). As a control, 16 fresh BMMC samples from healthy donors were analyzed. To control the quality of individual AML samples, hematoxylin and eosin staining of blast cells in AML samples was performed or AML marker expression was monitored using flow cytometry/FACS analysis. Sample processing was optimized to maximize cell viability during sample isolation. Optimal labeling times for AML samples were determined to ensure efficient labeling without compromising cell integrity.

Target surface antigen profiling was used to identify and quantify the repertoire of cell surface proteins in the samples. The extracellular domains of proteins associated with the cell membranes of intact primary tumor cells with AML were chemically labeled and then chromatographically enriched for the labeled proteins using solid-phase affinity chromatography resin. Eluted proteins were stored at -80°C before mass spectrometry analysis as described below.

sTAg-enriched proteins were identified and quantified using high-performance liquid chromatography coupled with panoramic tandem mass spectrometry (MS). The ThermoFisher LTQ-ORBITRAP VELOS hybrid mass spectrometer, which combines the sensitivity of a linear ion trap with the high resolution and mass accuracy provided by a revolutionary new orbital ion trap mass analyzer (Olsen et al., Mol. Cell Proteomics, 8: 2759- 2769, 2009), coupled to a nanoflow liquid chromatography setup, was used for panoramic, bottom-up proteomics to identify and quantify proteins in fractions enriched in AML cell surface proteins (Yates et al., Annu. Rev. Biomed. Eng., 11: 49-79, 2009). Tryptic digests of enriched surface proteins were separated based on their hydrophobicity online using nanoflow liquid chromatography with dynamic recording of peptide masses and fragmentation spectra using a mass spectrometer. To establish peptide and protein identities, raw MS data were processed using the SEQUEST algorithm running on the Sorcerer 2 fast processing platform (Lundgren et al., Curr. Protoc. Bioinformatics, Chapter 13: Unit 13.3, 2009) to determine the best match between experimental fragmentation spectra and those determined in-silico from the human proteome. The obtained matches were statistically confirmed using the PEPTIDEPROPHET (Keller et al., Anal. Chem., 74: 5383-5392, 2002) and PROTEIN PROPHET (Nesvizhskii et al., Anal. Chem., 75: 4646-4658, 2003) algorithms. implemented using SCAFFOLD software (Proteome software) to ensure that the false positive rate (FDR) is as low as possible and thus only accurately identified proteins are included in the candidate pool.

Relative quantitative levels of identified proteins in sTAg samples were determined using the spectral counting (SC) method (reviewed in Neilson et al., Proteomics, 11: 535-553, 2011). The spectral counting method is based on the empirical demonstration that the number of correlated (positively identified) spectra associated with peptides from each protein strongly correlates with the relative amount of that protein in the original mixture (Liu et al., Anal. Chem., 76: 4193- 4201, 2004). The counting of the spectra of the identified peptides was carried out using a program from the SCAFFOLD software, which displays, sorts and filters the results of mass spectrometry data queried by SEQUEST. The raw data from the spectral counting method were converted to percent normalized spectral abundance factor (%NSAF) values (Zybailov et al., J. Proteome Res., 5: 2339-2347, 2006) to account for differences in protein size and variability in total protein concentration. Individual monoclonal antibodies were used to validate proteomic measurements using quantitative FACS analysis as an independent external criterion to validate sTAg mass spectrometry-based proteomic profiling results related to protein expression on the surface of primary tumor cells (see, e.g., Example 2).

Using sTAg analysis, C10orf54, having the amino acid sequence of SEQ ID NO: 1080, was identified as present on the surface of AML tumor cells. As shown in FIG. 1A, using the sTAg method, C10orf54 was identified in 7 of 30 primary samples with AML with an average %NSAF value of 0.06. In contrast, C10orf54 was not detected in any of the 16 BMMC samples from healthy donors. The AML marker, CD33, was identified in 11 of 30 AML samples with a mean %NSAF of 0.07 and in four of 16 normal BMMC samples with a mean %NSAF of 0.05. In FIG. 1 B shows a selection of sTAg samples shown in FIG. 1A. Based on this analysis, C10orf54 is likely to be expressed to a comparable extent to CD33 in samples obtained from AML patients and is expressed in a significant proportion of AML patients compared with matched normal controls.

EXAMPLE 2. EXPRESSION OF C10ORF54

A. Expression in AML

Flow cytometry studies were performed on 23 primary and 3 normal BM-MNC samples prepared as described in Example 1 using anti-C10orf54 antibodies to analyze the expression profile of C10orf54 in AML. Antibodies were labeled with AF647 or AF488 fluorochromes. Cells were counted and 500,000 cells/stain were used, resuspended in FACS buffer: RPMI medium (Roswell Park Memorial Institute medium), 4% HIFBS (heat inactivated fetal bovine serum), 0.02% NaN ₃ . Antibodies were incubated for 15 minutes at room temperature in the dark and then analyzed using a MACSQuant instrument (Miltenyl Biotec, Auburn, CA). This analysis was performed using FLOWJO software (TreeStar, Ashland, OR). The results of FACS analysis using the anti-C10orf54 antibody 76E1 are shown in FIG. 2.

B. Expression in tumor tissues compared to normal tissues

To determine the expression of the C10orf54 protein in various normal and tumor human tissues, studies were performed using tissue matrices (TMAs).

A variety of formalin-fixed, paraffin-embedded tissues were used, including TMA obtained from US Biomax (Rockville, MD) and Protein Biotechnologies (Ramona, CA). Formalin-fixed, paraffin-embedded sarcoma cells transfected with C10orf54, parental sarcoma cells, and human placenta cells were used as positive and negative controls. Antibody to C10orf54 (Novus Biologicals (Littleton CO80120) catalog no. NBP1-88967 C10orf54/B7-H5/PD-1H) was used at a dilution of 1:150 in citrate buffer, pH 6.0 for antigen retrieval.

Immunohistochemical staining was performed using a Dako Autostainer (Dako North America, Carpenteria, CA93013) at room temperature with PBS washes between steps.

Normal tissue expression of C10orf54 was primarily restricted to immune cells in most tissues assessed. C10orf54-positive blood vessels were observed in central nervous system (CNS) tissues, albeit at higher magnification, and C10orf54 expression appeared to be present on pericytes and immune system cells. Trophoblasts in the placenta were strongly positive for C10orf54. The only epithelial tissue that showed positive expression of C10orf54 was the reactive centers of the amygdala. However, this positive expression may be due to the presence of a large number of positive lymphocytes passing through the epithelium. Tissues with negative expression included glomeruli, renal tubules and ducts, hepatocytes and sinusoidal capillaries of the liver, alveoli and bronchi of the lungs, pancreatic islets and acini, cardiac muscle, prostate gland, ovaries, colon crypts, gastric glands and epithelium, skin glands and epithelium , thymus, uterus, adrenal glands, skeletal muscles, neurons of the central nervous system, bladder epithelium and large vessels.

Thus, overall, TMA studies of normal tissues showed the strongest positive staining for placental trophoblasts and positive staining for immune system cells in the small intestine (lamina propria), spleen, tonsil, ureter, and lung.

Studies of TMA tumor tissues unexpectedly showed the presence of C10orf54-positive cells in more than 99% of tumors with inflammation. These results are summarized in Table 34.

C. Expression in Myeloid Suppressor Cells (MDSCs) To determine C10orf54 expression levels in the MDSC subset (CD11b ⁺ leukocytes) of purified human peripheral blood mononuclear cells (PBMCs) from healthy donors, flow cytometry studies were performed as described below. Expression was assessed and quantified using labeled monoclonal antibody 76E1 in the following MDSC populations: monocytic (CD11b ⁺ /CD14 ⁺ /HLA-DR ^- ), granule cell (CD11b ⁺ /CD15 ⁺ /HLA-DR ^- ) and immature myeloid cells (CD11b ⁺ /CD15 ^- /HLA-DR ^- ). PBMC samples used in these experiments were obtained from ALLCELLS (Emeryville, CA).

Clone 76E1 antibody was labeled using Alexa Fluor 647. PBMC samples were obtained and labeled LIVE/DEAD Yellow (LDY). 100 μl (10 ⁶ cells) was added to the following: human Fc receptor (FcR) blocking reagent; cell line markers; CD11b-PE(phycoerythrin); CD14-APC(allophycocyanin)-Cy7; CD15-PerCP-Cy5.5; HLA-DR-PE-Cy7 and 1 μg of labeled antibody 76E1-AF647. After incubation for 30 minutes at 4°C in the dark, samples were washed and analyzed.

Mean fluorescence intensity (MFI) values were calculated for each sample using a MACSQuant analyzer. To determine C10orf54 copy number, the Quantum Simply Cellular anti-Mouse IgG kit (Bangs Laboratories, 815B) was used.

The percentage of 76E1-AF-647 ⁺ cells found in the three MDSC subsets is summarized in FIG. 26A. Likewise, C10orf54 copy numbers for each MDSC subpopulation are summarized in FIG. 26V.

Using the above analysis, it was possible to identify both Lin ^- /CD11b ⁺ leukocytes and MDSC subpopulations, for which the monocytic-type MDSC population was shown to exhibit the highest level of C10orf54 expression among PBMC samples from healthy subjects.

D. Expression in CD4 ⁺ /CD25 ⁺ T cells

To determine C10orf54 expression levels in naïve CD4 ⁺ /CD25 ⁺ T cells found in human PBMCs, flow cytometry studies were performed as described above. Expression was assessed and quantified using labeled monoclonal antibody 76E1 as described above. CD4 ⁺ /CD25 ⁺ T cells were isolated using the Human CD4 + /CD25 + Regulatory T Cell Isolation Kit (Miltenyi-Biotec, 130-091-301). Aliquots from each isolation stage (PBMC, CD4+ T cells, CD4+/CD25+ T cells) were analyzed for C10orf54 expression. MFI values were quantified using the Quantum Simply Cellular anti-Mouse IgG kit (Bangs Laboratories, 815B). To evaluate this methodology, human PBMC samples were obtained from ALLCELLS.

The analysis described above showed that C10orf54 is minimally expressed in CD4 ⁺ /D25 ⁺ T cells.

E. Expression in human melanoma

To determine the expression of C10orf54 in human melanoma tumor samples and to evaluate a large number of cell subtypes (macrophages, myeloid cells, T cells and tumor cells), immunohistochemical (IHC) staining and double immunofluorescence (IF) staining studies were performed as described below .

Three different types of melanoma were evaluated: two cutaneous soft tissue melanomas (M113044 and OD41239) and one lymph node metastatic melanoma (WD-12972). One soft tissue melanoma specimen (OD41239) was more than 90% tumor, while another soft tissue melanoma and a lymph node (LN) metastatic melanoma were characterized by a strong inflammatory response with fewer tumor cells present.

The antibodies used in this study are listed below in Table 35. In addition, in each melanoma tissue, Gp100, which is preferentially expressed at high levels in melanoma cells, was stained using IHC to determine the number of tumor cells in the tissue samples and the content of C10orf54-positive tumor cells. .

To perform double IF staining, frozen cryostat sections (8 μm) were fixed in a mixture of 75% 200 proof ethanol and 25% acetone for 5 minutes. A mixture of primary antibodies (2 different types, diluted in Dako Part No. S3022; diluted according to Table 35) was added to the samples and incubated for 1 hour. Secondary antibodies were then added at a ratio of 1:200 and incubated for 30 min. Coverslips with Prolong Gold + DAPI (ThermoFisher, part no. 36935) were added and allowed to dry overnight. An Olympus BX52 vertical fluorescence microscope was used to analyze the samples.

To perform IHC staining with the gp100 antibody, frozen cryostat sections (8 μm) were fixed in a mixture of 75% 200 proof ethanol and 25% acetone for 5 minutes. Endogenous peroxidase was blocked by incubation with Bloxall (Vector, cat. no. SP-6000) for 5 minutes. Samples were further blocked using an Avidin and Biotin Blocking Kit (BioLegend, Cat# SIG-31126) for 10 min each and a Protein Block Kit (Dako, Cat# 0909) for 30 min. gp100 primary antibody (Abcam, catalog no. ab37062; ratio 1:100) was added and incubated for 1 hour. Secondary biotinylated anti-rabbit antibody (Vector, catalog no. BA1000) was added at a ratio of 1:200 and incubated for 30 min. Streptavidin-HRP (horseradish peroxidase) conjugate staining was performed using the VECTASTAIN Elite ABC kit (Vector Laboratories, Cat. No. PK6100) for 30 min. DAB (3,3'-diaminobenzidine) staining (Sigma, cat. no. D4418) and counterstaining with Mayer's hematoxylin (EMS, cat. no. 26043-05) were also performed.

The results of the above experiments are briefly formulated below.

Gp100: Almost all tumor cells in all three melanoma tissue samples were C10orf54 negative.

CD3: M113044: a large number of T cells were very weakly C10orf54 positive. Approximately 30% of cells were C10orf54 positive/CD3 negative. OD41239: Very few T cells present and almost all CD3 positive cells were C10orf54 negative. WD-12972: Large numbers of T cells observed. Many of them were also weakly C10orf54 positive. T cells in the tumor were predominantly C10orf54 negative and there were many C10orf54 positive cells that were CD3 negative throughout the tumor tissue.

CD68: M113044: the majority of CD68 positive cells were C10orf54 negative). OD41239: a subset of CD68 positive cells were also C10orf54 positive. WD-12972: CD68-positive cells were mostly C10orf54-negative, although there were also some CD68-negative/C10orf54-positive cells.

CD11b: Almost all CD11b-positive cells were also C10orf54-positive. However, there were C10orf54-positive cells that were CD11b-negative in all three melanoma tumors.

PD-L1: PD-L1 positive cells were also overwhelmingly C10orf54 positive in all three tumors. Again, there were C10orf54 positive cells that were PD-L1 negative in all three melanomas.

To summarize, almost all gp100-positive melanoma tumor cells were C10orf54 negative in all three melanoma samples. There was great variability in the amount of inflammatory cell infiltrate in 3 different melanoma tissue samples. However, almost all CD11b- and PD-L1-positive cells in these melanomas were C10orf54-positive and most CD3-positive T cells were either C10orf54-negative or very weakly C10orf54-positive.

F. Expression in non-small cell lung cancer (NSCLC)

To determine C10orf54 expression levels in PBMCs from NSCLC patients, flow cytometry studies were performed as described below. To evaluate the CD11b, CD33, CD14 and CD15 subpopulations, expression was assessed and quantified using labeled monoclonal antibody 26A. Representative PBMC samples from healthy and clinically diagnosed NSCLC patients used in these studies were obtained from ALLCELLS (Emeryville, CA).

Clone 26A antibody was labeled using Alexa Fluor 647. PBMC samples were obtained. 100 μl (10 ⁶ cells) was added to the following: human FcR blocking reagent; cell line markers; CD11b-PE; CD14-APC-Cy7; CD15-PerCP-Cy5.5; HLA-DR-PE-Cy7 and 1 μg of labeled antibody 26a-AF647. After incubation for 30 minutes at 4°C in the dark, samples were washed, resuspended in DAPI working solution and analyzed.

Mean fluorescence intensity (MFI) values were calculated for each sample using a MACSQuant analyzer. To determine C10orf54 copy number, the Quantum Simply Cellular anti-Mouse IgG kit (Bangs Laboratories, 815B) was used.

C10orf54 expression was assessed in PBMC subsets from the NSCLC sample compared to the healthy patient sample as shown in FIG. 27. These results are summarized in Table 36, which shows the copy number of C10orf54 when expressed in subsets of cells.

In addition, studies using tissue arrays (TMAs) were performed to determine the expression of C10orf54 protein in NSCLC.

A variety of formalin-fixed, paraffin-embedded tissues were used, including TMA obtained from US Biomax (Rockville, MD). Formalin-fixed, paraffin-embedded sarcoma cells transfected with C10orf54 and parental sarcoma cells were used as positive and negative controls. Antibody to C10orf54 (Novus Biologicals (Littleton CO80120), catalog no. NBP1-88967 C10orf54/B7-H5/PD-1H) was used at a 1:150 dilution in citrate buffer, pH 6.0, for antigen retrieval.

Immunohistochemical staining was performed using a Dako Autostainer (Dako North America, Carpenteria, CA93013) at room temperature with PBS washes between steps.

For lung tumor TMAs containing all types of NSCLC tumors, all types of NSCLC were found to be characterized by positive expression of C10orf54. However, the number of samples in these TMAs was relatively small, with the exception of squamous cell carcinoma (SCC), for which a convincing pattern of C10orf54 expression was observed.

SCC subtype was further assessed for four additional TMAs. Additional survival data were available for two TMAs. However, no correlation was observed when these data were analyzed as a function of the percentage of C10orf54-positive cells. For one TMA, epidermal growth factor receptor (EGFR) expression data were also available, but no correlation was observed when analyzed as a function of the percentage of C10orf54-positive cells. For this TMA, the number of samples may have been too small to determine a true correlation. Pooled data for all four TMAs in SCC were also assessed. Samples were divided according to the degree of inflammation present in the analyzed areas of inflammation. When no inflammation was observed, no C10orf54-positive cells were detected. However, it is surprising that the majority of samples with mild to severe inflammation had C10orf54-positive infiltrating cells. For example, in one TMA of SCC, 17% showed no inflammation, 28% showed mild inflammation, and 55% showed moderate inflammation. Of the 28% who showed mild inflammation, 85% were C10orf54 positive, and of the 55% who showed moderate inflammation, 92% were C10orf54 positive.

Thus, the above analyzes indicate an increase in the C10orf54 population in each subset compared to the healthy donor. Similarly, a higher copy number of C10orf54 was observed in samples from NSCLC patients compared to healthy donors. In addition, NSCLC with inflammation was strongly correlated with C10orf54 expression.

EXAMPLE 3. OBTAINING MONOCLONAL ANTIBODIES TO C10ORF54

Antibodies to C10orf54 were generated using the iTAb platform. In this system, a mouse tumor cell line is transduced to stably express a human protein and then implanted subcutaneously into syngeneic mice. Mice are treated with an anti-CD8 antibody to remove cells that mediate the rejection pathway while leaving the humoral immune response unaffected. After this immunization, splenocytes are collected and fused with an immortalized partner cell to produce a hybridoma. Antibodies from these hybridomas are screened in several assays designed to identify a diverse panel of antibodies with good binding properties. The selected antibodies are then developed for in vivo testing as follows.

Mouse sarcoma cell lines expressing C10orf54 were generated by viral infection of the sarcoma cell lines. The PCR-amplified C10orf54 gene was cloned into a mouse stem cell viral expression vector with a neomycin resistance gene and sequenced to confirm identity. To produce viral particles, HEK 293t cells with retroviral packaging proteins were transfected in the presence of FUGENE HD transfection reagent (Roche) with a retroviral expression vector containing the C10orf54 gene. Viral particles collected from the supernatant of culture media 48 hours after transfection were used to infect sarcoma cells. After selection using G418, stable transfectants were pooled and then cloned by limiting dilution. Then, clones were selected and grown in the presence of antibiotics. Clones with the highest levels of C10orf54 expression as measured by flow cytometry were grown and banked. These cell lines were then used to immunize syngeneic mice to generate antibodies and in binding assays to select antibodies, as follows.

For immunization, a mouse sarcoma cell line expressing C10orf54 was implanted subcutaneously into 129s6/SvEv mice, which are syngeneic with the sarcoma line. Mice were reintroduced to the cell line three days before spleen collection. Splenocytes were isolated as single cells and fused with SP2-MIL6 cells using PEG1500. The resulting hybridomas were seeded into 384-well plates and left to grow for ten days.

Antibodies to C10orf54 were initially selected using a cell-based enzyme-linked immunosorbent assay (ELISA) to detect binding to C10orf54. To perform this assay, C10orf54-expressing sarcoma cells were seeded in 384-well plates one day before the assay. Cells were then treated with hybridoma supernatants. After incubation and washing, the presence of bound antibody was detected using peroxidase-conjugated goat anti-mouse IgG (Jackson ImmunResearch Laboratories) followed by the addition of a chemiluminescent substrate (ThermoScientific SuperSignal ELISA Pico Substrate). Hybridomas identified as positive in the initial screening were transferred to wells of a 96-well plate. After growth, supernatants were tested in a similar assay for confirmation.

Antibody isotype was identified using ELISA using isotype-specific goat anti-mouse Fc antibodies. For this assay, C10orf54-expressing cells were seeded in 384-well plates one day before the assay. Cells were then treated with hybridoma supernatants. After incubation and washing, cells were incubated with peroxidase-conjugated goat antibody specific for mouse IgG1 or IgG2a (Jackson ImmunResearch Laboratories), followed by the addition of a chemiluminescent substrate (ThermoScientific SuperSignal ELISA Pico Substrate).

The concentration of antibody in supernatants found to be positive for binding to C10orf54-expressing cells was measured using ELISA. Supernatants were tested in four dilutions. For each antibody, a dilution giving a value within the linear range of the standard curve was used to calculate the antibody concentration in the supernatant. The concentration of antibodies in the supernatants ranged from 1 μg/ml to 500 μg/ml, with approximately 300 supernatants being greater than 10 μg/ml. Twenty-two monoclonal antibodies were selected based on binding to C10orf54 and further analyzed in vitro and in vivo as described herein.

Sequences of selected twenty-two monoclonal antibodies (5B, 46A, 97A, 128A, 146C, 208A, 215A, 26A, 164A, 230A, 76E1, 53A, 259A, 33ZA, 39A, 124A, 175A, 321D, 141A, 51 A, 53A, 305A) are shown below.

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of the 5B antibody are shown below.

Antibody heavy chain variable region 5B with signal sequence:

Antibody light chain variable region 5B with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 46A are shown below.

Antibody 46A heavy chain variable region with signal sequence:

Antibody 46A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 97A are shown below.

Antibody 97A heavy chain variable region with signal sequence:

Antibody 97A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 128A are shown below.

Antibody 128A heavy chain variable region with signal sequence:

Antibody 128A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 146C are shown below.

Variable region of the heavy chain of antibody 146C with signal sequence:

Antibody 146C light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 208A are shown below.

Antibody 208A heavy chain variable region with signal sequence:

Antibody 208A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 215A are shown below.

Antibody 215A heavy chain variable region with signal sequence:

Antibody 215A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 26A are shown below.

Antibody 26A heavy chain variable region with signal sequence:

Antibody 26A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 164A are shown below.

Antibody 164A heavy chain variable region with signal sequence:

Antibody 164A light chain variable region with signal sequence:

Antibody 164A light chain variable region, number 2, with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 230A are shown below.

Antibody 230A heavy chain variable region with signal sequence:

Antibody 230A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 76E1 are shown below.

Variable region of the heavy chain of antibody 76E1 with signal sequence:

Variable region of the light chain of antibody 76E1 with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 53A are shown below.

Antibody 53A heavy chain variable region with signal sequence:

Antibody 53A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 259A are shown below.

Antibody 259A heavy chain variable region with signal sequence:

Antibody 259A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 33A are shown below.

Antibody 33A heavy chain variable region with signal sequence:

Antibody 33A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 39A are shown below.

Antibody 39A heavy chain variable region with signal sequence:

Antibody 39A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 124A are shown below.

Antibody 124A heavy chain variable region with signal sequence:

Antibody 124A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 175A are shown below.

Antibody 175A heavy chain variable region with signal sequence:

Antibody 175A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 321 D are shown below.

Antibody 321D heavy chain variable region with signal sequence:

Antibody 321D light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 141A are shown below.

Antibody 141A heavy chain variable region with signal sequence:

Antibody 141A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 51A are shown below.

Antibody 51A heavy chain variable region with signal sequence:

Antibody 51A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 353A are shown below.

Antibody 353A heavy chain variable region with signal sequence:

Antibody 353A light chain variable region with signal sequence:

The nucleic acid and amino acid sequences for the heavy chain and light chain variable regions of antibody 305A are shown below.

Antibody 305A heavy chain variable region with signal sequence:

Antibody 305A light chain variable region with signal sequence:

The CDR sequences for the selected twenty-two monoclonal antibodies are shown in Tables 12-33 and were used to obtain humanized antibodies kC10ogt54.

EXAMPLE 4. SORTING AND EPITOPE MAPPING OF ANTIBODIES TO C10ORF54

The VH and VK (variable kappa chain) paratope diversity of 22 human C10orf54 antibodies was assessed by analyzing the variable region sequences. Each nucleotide sequence was searched using IMGT/V-Quest (IMGT®, international information system ImMunoGeneTics, http://www.imgt.org (founder and director: Marie-Paule Lefranc, Montpellier, France)), and the germline gene sequence lines with the highest degree of identity to the query sequence were placed in the table (Table 37). Antibodies with the same germline VH and VK gene sequences were placed in the same paratope group (Table 37).

To examine the epitope diversity of anti-human C10orf54 antibodies, 293t cells were transfected using 1 of 10 different C10orf54-expressing constructs that also expressed a fluorescent marker. The C10orf54 proteins and chimeric proteins encoded by the constructs used are shown in Table 38. Two days after transfection, the cells were separated from the tissue culture plate, treated with a solution of anti-human C10orf54 antibody (2 μg/ml), washed, treated with a polyclonal antibody to IgG- Alexa Fluor 647-conjugated mouse Fc was washed and treated with 4',6-diamidino-2-phenylindole dihydrochloride dye to determine viability. After detection of 10,000 live “events” on the flow cytometer, live cells labeled with a fluorescent marker were analyzed for the degree of staining with the human kC10ogm54 antibody. When the average fluorescence intensity relative to the isotype control antibody increased at least 20-fold, the antibody was considered to “color” the C10orf54-expressing construct in question. The results of these sorting experiments and the description of the bins of constructs are shown in Table 39.

The amino acid sequences for the C10orf54 proteins and chimeric proteins encoded by the expression constructs are shown below.

The amino acid sequence for the human C10orf54 protein encoded by the CC1 expression construct is shown below:

The amino acid sequence of the mouse C10orf54 protein encoded by the CC2 expression construct is shown below:

The amino acid sequence of the rat C10orf54 protein encoded by the CVD expression construct is shown below:

The amino acid sequence of the cynomolgus C10orf54 protein encoded by the CC4 expression construct is shown below:

The amino acid sequence of the chimeric protein encoded by the CC5 expression construct is shown below:

The amino acid sequence of the chimeric protein encoded by the CC6 expression construct is shown below:

The amino acid sequence of the chimeric protein encoded by the CC7 expression construct is shown below:

The amino acid sequence of the chimeric protein encoded by the CC8 expression construct is shown below:

The amino acid sequence of the chimeric protein encoded by the CC9 expression construct is shown below:

The amino acid sequence of the chimeric protein encoded by the CC10 expression construct is shown below:

The results of these experiments demonstrate that the anti-C10orf54 antibodies described herein bind to various epitopes of human C10orf54, including AA33-169, AA84-169, AA115-169 and AA84-115.

EXAMPLE 5. OBTAINING HUMANIZED ANTIBODIES

Mouse antibodies prepared as described in Example 3 were selected for sequencing. These selected monoclonal antibodies, designated 76E1, 141A and 175A, were humanized in two ways, as follows. The results of humanization are shown in FIG. 3-8.

In the first humanization method, most of the amino acids in each complementarity determining region (CDR) that were previously identified, the heavy chain variable domain (VH) and light chain variable domain (VL) sequences were converted to alanine. The resulting sequence for VH and for VL, shown in FIG. 9 were used as input for the human subgroup identification algorithm on the Dr. website. Andrew C.R. Martin www.bioinf.org.uk/abs/; this method is a variation taken from Deret, S. et al., SUBIM: a Program for Analyzing the Kabat Database and Determining the Variability Subgroup of a new Immunoglobulin Sequence, Comput. Appl. Biosci., 11: 435-439 (1995). VH antibodies 76E1, VH antibodies 141A and VH antibodies 175A were most similar to subgroup I of human VH immunoglobulin, VL antibodies 76E1 and VL antibodies 175A were most similar to subgroup II of human VL-kappa immunoglobulin, and VL of antibody 141A was most similar to subgroup III Human immunoglobulin VL-kappa. For each mouse VH and VL sequence of antibodies 76E1, 141A and 175A, one human germline VH or VL acceptor sequence was selected from the corresponding subset of human germline sequences and all connecting region sequences assembled using IMGT®, the international information system ImMunoGeneTics , www.imgt.org (founder and director: Marie-Paule Lefranc, Montpellier, France)).

In the second humanization method (Carter et al., Proc. Natl. Acad. Sci. USA, 89: 4285-4289 (1992)) as an acceptor for mouse VH sequences - VH antibodies 76E1, VH antibodies 141A and VH antibodies 175A - human germline immunoglobulin subgroup III VH was used; Subgroup I of human VL-kappa immunoglobulin was used as an acceptor for VL antibody 76E1, VL antibody 141A and VL antibody 175A.

To optimize the binding of a humanized antibody, it may be necessary to change positions of the human germline antibody framework (eg, non-CDR residues in VH and VL) to the corresponding positions of the mouse parental sequence 76E1, 141A, or 175A. Possible changes for each humanized sequence are noted in FIG. 3-8. Possible changes in the CDR sequences of humanized antibodies to alleviate complications caused by deamidation of solvent-exposed asparagine residues, oxidation of solvent-exposed methionine residues, and formation of isoaspartic acid are also noted in FIG. 3-8.

Computational graphics models of the VH and VL domains of mouse antibodies 76E1, 141A and 175A were developed to assist in the selection of CDR residues and framework residues that may require modification. The Swiss-PdB Viewer program was used (Guex, N. and Peitsch, M.C., SWISS-MODEL and the Swiss-PdBViewer: An environment for comparative protein modeling. Electrophoresis, 18: 2714-2723 (1997). Protein Analysis Expert System website (ExPASY) Antibody crystal structures were taken from the Protein Structure Data Bank website (Berman, N.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov , I.N., Bourne P.E., The Protein Data Bank Nucleic Acids Research, 28: 235-242 (2000). The sequences of the VH and VL domains of the humanized antibodies 76E1, 141A and 175A are shown in FIGS.

Additional humanized anti-C10orf54 antibodies containing VH domain, VL domain, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and/or VL CDR3 were generated and are shown in Tables 12-33. For example, individual mouse monoclonal antibodies designated 26A, 128A, 124A and 259A were humanized using the following method, the results of which are shown in FIG. 22A, 22B, 23A, 23B, 24A, 24B, 25A and 25B. The CDR sequences and VH/VL sequences for antibodies designated 26A, 128A, 124A and 259A are shown in Tables 19, 15, 27 and 24, respectively.

The VH and VL sequences of each mouse mAb were used as input to the IgBLAST program on the National Center for Biotechnology Information (NCBI) website (http://www.ncbi.nlm.nih.gov/igblast/; Ye, J. et al., Nucleic Acids Research, 41: W34-W40 (2013)). IgBLAST uses a mouse VH or VL sequence and compares it to a library of known human germline antibody sequences. The databases used were IMGT for human VH genes (F+ORF, 273 germline sequences) and IMGT for human VL-kappa genes (F+ORF, 74 germline sequences). IgBLAST produces the top 10 human germline antibody sequences as scored.

For all four VH antibodies 26A, 128A, 124A and 259A, the germline sequence of the human antibody IGHV1-46 (allele 1) was selected as the acceptor sequence, and the connecting region (J gene) of the heavy chain of the human antibody IGHJ4 (allele 1) was selected from the sequences connecting regions of human antibodies collected using the international information system ImMunoGeneTics, IMGT®, www.imgt.org (see FIGS. 22A, 23A, 24A and 25A).

For VL antibody 26A, the germline sequence of human antibody IGKV43-11 (allele 1) was selected as the acceptor sequence, and the light chain connecting region (J gene) of human antibody IGKJ2 (allele 1) was selected from human antibody connecting region sequences assembled using international information system ImMunoGeneTics, IMGT®, www.imgt.org (see FIG. 22B).

For VL antibody 128A, the human antibody germline sequence IGKV1-39 (allele 1) was selected as the acceptor sequence, and the human antibody light chain sequence IGKJ2 (allele 1) was selected as the connecting region (J gene) (see FIG. 23B).

For VL antibody 124A, the germline sequence of the human antibody IGKV2-30 (allele 1) was selected as the acceptor sequence, and the light chain sequence of the human antibody IGKJ2 (allele 1) was selected as the connecting region (J gene) (see FIG. 24B).

For VL antibody 259A, the germline sequence of the human antibody IGKV2-28 (allele 1) was selected as the acceptor sequence, and the light chain sequence of the human antibody IGKJ2 (allele 1) was selected as the connecting region (J gene) (see FIG. 25B).

EXAMPLE 6. ANTI-TUMOR ACTIVITY

Antibodies to C10orf54 were tested for their antitumor activity in an animal tumor model. For these studies, the Kasumi-3 (acute myeloid leukemia) cell line was obtained from ATCC (CRL-2725) and cultured according to the suppliers' protocols. Animals were obtained from Taconic (Hudson, NY). Studies were carried out with antibodies to C10orf54 on an animal model of tumors.

In these experiments, 4-6 week old female non-obese combined immunodeficiency-diabetic (NOD-SCID) immunodeficient mice were used in the Kasumi-3 tumor model. Mice were injected subcutaneously into the right flank with 1.2 x 10 ⁶ viable cells (Kasumi-3) in a 1:1 mixture of PBS (without magnesium or calcium) and BD Matrigel (BD Biosciences). The total volume administered per mouse was 200 μl, of which 50% was Matrigel (BD Biosciences). After tumor size reached 65-200 mm ³ , mice were randomized. Antibodies were administered once weekly at a dose of 15 mg/kg for four weeks, and body weight and tumor size were measured once and twice weekly, respectively. Tumor volume was calculated as described (van der Horst et al., 2009, Neoplasia, 11(4): 355-364). Experiments were carried out in groups of at least 8 animals per experimental point.

Statistical significance between treatment and control groups was calculated using the Graphpad Prism software package and using a two-tailed Student's t test. A p value less than 0.05 was considered significant. The results of three representative experiments are shown in Table 40. In the case of experiment 1, the tumor volumes at which treatment began were 114.7 mm ³ (day 96). In the case of experiment 2, the tumor volumes at which treatment began were 114.5 mm ³ (day 103). In the case of experiment 1, the tumor volumes at which treatment began were 133 mm ³ (day 34).

As shown in FIG. 10 (also see Table 40, experiment 1), treatment with anti-C10orf54 antibody caused strong tumor growth inhibition in established Kasumi-3 tumors. Treatment with either antibody had no significant effect on body weight, indicating that antibody treatment was not toxic. As shown in FIG. 11 (also see Table 40, experiment 3), repeated treatment with antibody 175A caused strong tumor growth inhibition in established Kasumi-3 tumors.

EXAMPLE 7. PREPARATION AND APPLICATION OF ANTIBODY-DRUG CONJUGATES

Antibody-drug conjugates (ADCs) were prepared and used in secondary ADC assays and ADC assays where anti-C10orf54 antibodies are directly conjugated to a cytotoxin, as illustrated in the following typical general scheme A, where a maleimido group is attached to the cytotoxin (CTX) via a linker ( L):

For example, according to the above diagram, A, L may be one of the following:

(1) -(CH ₂ ) ₅ -C(O)-; (2) -(CH ₂ ) ₅ -C(O)-valine-citrulline; (3) -(CH ₂ ) ₅ -C(O)-valine-alanine; (4) -(CH ₂ ) ₅ -C(O)-valine-citrulline-phenylenyl, where the phenylenyl is substituted with 2 substituents selected from the group consisting of -C(O)OH and -NH ₂ ; (5) -(CH ₂ ) ₅ -C(O)-valine-alanine-phenylenyl, where the phenylenyl is substituted with 2 substituents selected from the group consisting of -C(O)OH and -NH ₂ ; (6) -(CH ₂ CH ₂ )-(CH ₂ CH ₂ O) ₄ -C(O)-valine-citrulline-phenylenyl, where phenylenyl is substituted with 2 substituents selected from the group consisting of -C(O) OH and -NH ₂ ; or (7) -(CH ₂ CH ₂ )-(CH ₂ CH ₂ O) ₄ -C(O)-valine-alanine-phenylenyl, wherein the phenylenyl is substituted with 2 substituents selected from the group consisting of -C(O )OH and -NH ₂ .

For example, according to the above scheme A, L may be one of the following: (1) caproyl ("c"); (2) caproyl-valine-citrulline (“cValCit”); (3) caproyl-valine-alanine (“cValAla”); (4) caproyl-valine-citrulline-p-aminobenzyl (“cValCit-PAB”); (5) caproyl-valine-alanine-p-aminobenzyl (“cValAla-PAB”); (6) (dPEG) ₄ -valine-citrulline-p-aminobenzyl (“dPEG ₄ -ValCit-PAB”); or (7) (dPEG) ₄ -valine-alanine-para-aminobenzyl ("dPEG ₄ -ValAla-PAB").

For example, when an antibody-drug conjugate is prepared using a maleimide group ("m") attached to a cytotoxin, CTX, via a linker, as illustrated in Scheme A above, the antibody-drug conjugate may comprise one of the following: (1) maleimidocaproyl ("mc"); (2) maleimidocaproyl-valine-citrulline (“mcValCit”); (3) maleimidocaproyl-valine-alanine (“mcValAla”); (4) maleimidocaproyl-valine-citrulline-p-aminobenzyl (“mcValCit-PAB”); (5) maleimidocaproyl-valine-alanine-p-aminobenzyl (“mcValAla-PAB”); (6) maleimidocaproyl-(dPEG) ₄ -valine-citrulline-p-aminobenzyl (“m-dPEG4-ValCit-PAB”); or (7) maleimidocaproyl-(dPEG) ₄ -valine-alanine-p-aminobenzyl (“m-dPEG4-ValAla-PAB”).

As illustrated in the following Schemes BF, the antibody-drug conjugate of Scheme A above can be prepared using maleimidocaproyl-monomethyl auristatin F ("mc-MMAF"), maleimidocaproyl-valine-citrulline-p-aminobenzyl-monomethyl auristatin F ("mcValCit-PAB-MMAF"), maleimidocaproyl-valine-citrulline-p-aminobenzyl-monomethyl auristatin E ("mcValCit-PAB-MMAE"), maleimidocaproyl-(dPEG) ₄ -valine-citrulline-p-aminobenzyl-CC1065 ("m- dPEG ₄ -ValCit-PAB-CC1065") or maleimidocaproyl-valine-alanine-pyrrolobenzodiazepine ("mcValAla-PBD").

Typical antibody-drug conjugates are prepared using maleimidocaproyl-monomethyl auristatin F (mc-MMAF), as illustrated in the following Scheme B, where a maleimido group is attached to the cytotoxin (CTX is MMAF) via a linker (L is a caproyl group):

Typical antibody-drug conjugates are also prepared using maleimidocaproyl-valine-citrulline-p-aminobenzyl-

monomethyl auristatin F (mcValCit-PAB-MMAF), as illustrated in the following Scheme C, where a maleimido group is attached to the cytotoxin (CTX is MMAF) via a linker (L is caproyl-valine-citrulline-p-aminobenzyl):

Typical antibody-drug conjugates are also prepared using maleimidocaproyl-valine-citrulline-p-aminobenzyl-monomethyl auristatin E (mcValCit-PAB-MMAE), as illustrated in the following Scheme D, where the maleimido group is attached to the cytotoxin (CTX is MMAE) via linker (L is caproyl-valine-citrulline-p-aminobenzyl):

Typical antibody-drug conjugates are also prepared using maleimidocaproyl-(dPEG) ₄ -valine-citrulline-p-aminobenzyl-CC1065 (m-dPEG ₄ -ValCit-PAB-CC1065), as illustrated in the following Scheme E, where the maleimido group attached to the cytotoxin (CTX is CC1065) via a linker (L is (dPEG) ₄ -valine-citrulline-p-aminobenzyl):

In Scheme E, the structure of the cyclophosphamide, CC1065, is shown in the lower left corner of the diagram, with an arrow indicating the site of attachment (for example, through the free amino group on the CC1065 molecule) to the carbonyl group of the para-aminobenzoate moiety of the linker.

Typical antibody-drug conjugates are also prepared using maleimidocaproyl-valine-alanine-pyrrolobenzodiazepine (mc-ValAla-PBD), as illustrated in the following Scheme F, where a maleimido group is attached to the cytotoxin (CTX is a PBD), via a linker (L is caproyl-valine-alanine):

The ADCs shown in exemplary Schemes B-F were prepared as follows. In sterile 1.7 ml Eppendorf tubes, 20 mg of antibody was reacted at a concentration of 20 mg/ml in phosphate buffered saline (PBS), pH 7.4 (Gibco; free of Mg and Ca) with 1 mM diethylenetriaminepentaacetic acid ( DTPA) as a chelator. Then 2.75 eq. was added. tris(2-carboxyethyl)phosphine hydrochloride (TCEP HCl) solution (Sigma; ampoule concentration 0.5 M) or 50 μl of 100 mM dithiothreitol (DTT) solution at an average drug-to-antibody ratio (DAR) of 4 moles of drug per mole of antibody, and incubated at 37°C for 1 hour so that the content of “unlabeled” or free antibodies was less than 10% of the total antibody content.

A colorimetric assay using dithio-bis-nitrobenzoate (DTNB; Ellman's reagent) was used to estimate the content of free thiols suitable for conjugation (Ellman et al., Biochemical Pharmacology, 7: 88-95 (1961)). The reduced antibody solution was cooled in an ice bath at approximately 0°C for 15 minutes. The linker-cytotoxin conjugate was then added to the reconstituted antibody solution as follows: (1) for regimen B, 60 μl of mc-MMAF from a 10 mM concentrated solution in DMSO was added (9.74 mg in 1.074 ml DMSO to a concentration of 10 mM); (2) for scheme C, 60 μl of mcValCit-PAB-MMAF from a 10 mM concentrated solution in DMSO was added (9.4 mg in 707 μl DMSO to a concentration of 10 mM); (3) for scheme D, 60 μl of mcValCit-PAB-MMAE from a 10 mM concentrated solution in DMSO was added (3.24 mg in 247 μl DMSO to a concentration of 10 mM); (4) for scheme E, 60 μl of ts-dPEG4-ValCit-PAB-CC1065 was added from a 10 mM concentrated solution in DMSO (3.8 mg in 258 μl DMSO to a concentration of 10 mM); and (5) for scheme F, 60 μl of mc-ValAla-PBD from a 10 mM concentrated solution in DMSO was added. After adding the linker-cytotoxin conjugate to the reconstituted antibody solution, the solution was incubated on a roller plate in a refrigerator at 4°C overnight (or alternatively at 37°C for 2 hours) to prepare the ADC. The DTNB assay was repeated to demonstrate the absence of remaining free thiols (a colorless solution indicates no free thiols and a yellow color indicates the presence of remaining free thiols and incomplete conjugation of the starting material). ADC concentration was determined using a NanoDrop spectrophotometer. The crude ADC was purified using either PD-10 gel chromatography (SEC) separation or SEC chromatography on a Sephadex G-200 column, eluting with an appropriate running buffer or buffer to obtain the final composition. Purified ADC was stored at 4°C.

The hydrophobic interaction chromatography (HIC) method, a variant of high performance liquid chromatography (HPLC), was used to determine the average drug content of the ADC. Using an Agilent 1200 binary pump HPLC system coupled to an Agilent 6130b electrospray mass spectrometer, an NPR Butyl-C4 column from Tosoh (2.1 mm × 75 mm) was used with a binary gradient at a flow rate of 0.8 mL/min with detection at 220 nm, 254 nm and 280 nm, using a diode array detector with the ability to register in the ultraviolet and visible regions of the spectrum. Mobile phase A was 1.5 M sodium sulfate in 1xPBS, mobile phase B was 1xPBS with 25% isopropanol, eluting with a 0-100% linear gradient in an amount of 10-12 column volumes with an initial equilibration of 5 minutes and washing with 100% mobile phase B for 5 minutes at the end of each HPLC analysis. The "unlabeled" or free antibody eluted first along the linear gradient, with peaks corresponding to increasing average drug content in the order of hydrophobicity, which correlates with increasing antibody content of the starting material. Retention times for free antibody were confirmed by assay using a standard injection of 20 μl of a concentrated solution (1 mg/ml) of antibody. By co-eluting free antibody and ADC, the relative amounts of each were finally confirmed.

In FIG. 12 shows the results of a secondary ADC assay using anti-C10orf54 antibodies in a cell viability assay using a C10orf54-expressing sarcoma line. Antibodies to C10orf54 were incubated at a 2:1 ratio with secondary goat anti-mouse MMAF-conjugated antibody. Cells were seeded at 1000 cells/well and incubated in the presence of antibodies for 72 hours. Depletion of these C10orf54-expressing sarcoma cells was accomplished using anti-C10orf54 antibodies tested in a concentration-dependent manner.

In FIG. 13-14 show the activity of unconjugated anti-C10orf54 antibodies and anti-C10orf54 antibodies directly conjugated to MMAE in cell viability assays using C10orf54-expressing sarcoma lines. To perform these assays, cells can be seeded in various numbers into wells and incubated for various periods of time in the presence or absence of antibodies to C10orf54 and ADC. For example, for the analyzes shown in FIG. 13, cells were seeded at 1000 cells/well and incubated in the presence of antibodies for 72 hours. In these in vitro cell-based assays, MMAF-conjugated anti-C10orf54 antibodies killed sarcoma cells in a concentration-dependent manner.

In FIG. 15 shows the results of treatment with anti-C10orf54 antibodies and ADCs (eg, unconjugated and MMAF-conjugated anti-C10orf54 antibodies) in an animal tumor model (eg, xenograft model) of C10orf54-expressing and parental sarcoma lines.

EXAMPLE 8. PREPARATION AND USE OF ADDITIONAL ANTIBODY-DRUG CONJUGATES

Additional antibody-drug conjugates of formula (Ia) or (Ib) of the present invention can be prepared as illustrated by formula (Ia) in the following Scheme G and formula (Ib) in the following Scheme H:

Additional antibody-drug conjugates of the present invention can be prepared, wherein the antibody-drug conjugates have formula (Ic1):

or a pharmaceutically acceptable salt thereof,

Where:

A is an antibody, wherein the antibody is an anti-C10orf54 antibody, possibly a humanized anti-C10orf54 antibody;

the two cysteine residues depicted are formed by the opening of the cysteine-cysteine disulfide bond in A;

L is a cleavable or non-cleavable linker;

CTX is a cytotoxin linked to an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond; And

n is equal to an integer from 1 to 4.

For example, antibody-drug conjugates of formula (Ic1) are prepared wherein CTX is monomethyl auristatin F (MMAF), L is -( _CH2 ) _5C (O)-, and n is 4.

For example, antibody-drug conjugates of formula (Ic1) are prepared, wherein the antibody-drug conjugate has the following formula:

where A is an anti-C10orf54 antibody, possibly a humanized anti-C10orf54 antibody, and n is 4.

For example, antibody-drug conjugates of formula (Ic1) are those wherein CTX is monomethyl auristatin E (MMAE), L is -(CH ₂ ) ₅ C(O)-Val-Ala-PAB-OC(O)- or -(CH ₂ ) ₅ C(O)-Val-Cit-PAB-O-C(O)-, and n is 4.

For example, antibody-drug conjugates of formula (Ic1) are those having the following formula:

where A is an anti-C10orf54 antibody, possibly a humanized anti-C10orf54 antibody, and n is 4.

For example, antibody-drug conjugates of formula (Ic1) are those wherein CTX is pyrrolobenzodiazepine (PBD), L is -(CH ₂ ) ₅ C(O)-Val-Ala-PAB-OC(O)- or - (CH ₂ ) ₅ C(O)-Val-Cit-PAB-O-C(O)-, and n is 4.

For example, antibody-drug conjugates of formula (Ic1) are those that have one of the following formulas:

And

Antibody-drug conjugates of formula (Ic1) are prepared using linker-cytotoxin conjugates of formula (IIa) below:

or an enantiomer, diastereomer or mixtures thereof;

Where:

L is a cleavable or non-cleavable linker; And

CTX is a cytotoxin linked to an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond.

For example, antibody-drug conjugates of formula (Ic1) are prepared using anti-C10orf54 antibodies (eg, humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate of formula (Ia) wherein CTX is MMAF and L is -( _CH2 ) ₅ C(O)-.

For example, antibody-drug conjugates of formula (Ic1) were prepared using anti-C10orf54 antibodies (e.g., humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate that has the following structure:

For example, antibody-drug conjugates of formula (Ic1) are prepared using anti-C10orf54 antibodies (eg, humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate of formula (IIa) wherein CTX is MMAE and L is -(CH ₂ ) ₅ C(O)-Val-Ala-PAB-O-C(O)- or -(CH ₂ ) ₅ C(O)-Val-Cit-PAB-OC(O).

For example, antibody-drug conjugates of formula (Ic1) are prepared using anti-C10orf54 antibodies (e.g., humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate that has the following structure:

For example, antibody-drug conjugates of formula (1c1) are prepared using anti-C10orf54 antibodies (eg, humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate of formula (IIa) wherein CTX is PBD and L is -(CH ₂ ) ₅ C(O)-Val-Ala-, -(CH ₂ ) ₅ C(O)-Val-Cit-, -(CH ₂ ) ₅ C(O)-Val-Ala-PAB-OC(O) - or -(CH ₂ ) ₅ C(O)-Val-Cit-PAB-OC(O)-.

For example, antibody-drug conjugates of formula (Ic1) are prepared using anti-C10orf54 antibodies (e.g., humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate that has one of the following structures:

Additional antibody-drug conjugates of the present invention can be prepared, wherein the antibody-drug conjugates have formula (Ic2):

or a pharmaceutically acceptable salt thereof,

Where:

A is an antibody, wherein the antibody is an anti-C10orf54 antibody, possibly a humanized anti-C10orf54 antibody;

the two cysteine residues depicted are formed by the opening of the cysteine-cysteine disulfide bond in A;

L is a cleavable or non-cleavable linker;

CTX is a cytotoxin linked to an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond; And

n is equal to an integer from 1 to 4.

For example, antibody-drug conjugates of formula (Ic2) are prepared wherein CTX is monomethyl auristatin F (MMAF), L is -( _CH2 ) _5C (O)-, and n is 4.

For example, antibody-drug conjugates of formula (Ic2) are prepared, wherein the antibody-drug conjugate has the following formula:

where A is an anti-C10orf54 antibody, possibly a humanized anti-C10orf54 antibody, and n is 4.

For example, antibody-drug conjugates of formula (Ic2) are those wherein CTX is monomethyl auristatin E (MMAE), L is -(CH ₂ ) ₅ C(O)-Val-Ala-PAB-OC(O)- or -(CH ₂ ) ₅ C(O)-Val-Cit-PAB-O-C(O)-, and n is 4.

For example, antibody-drug conjugates of formula (Ic2) are those having the following formula:

where A is an anti-C10orf54 antibody, possibly a humanized anti-C10orf54 antibody, and n is 4.

For example, antibody-drug conjugates of formula (Ic2) are those wherein CTX is pyrrolobenzodiazepine (PBD), L is -( _CH2 ) _5C (O)-Val-Ala-PAB-OC(O)- or - (CH ₂ ) ₅ C(O)-Val-Cit-PAB-O-C(O)-, and n is 4.

For example, antibody-drug conjugates of formula (Ic2) are those that have one of the following formulas:

And

Antibody-drug conjugates of formula (Ic2) are prepared using linker-cytotoxin conjugates of one of the following formulas (IIb) and (IIc):

or an enantiomer, diastereomer or mixtures thereof;

Where:

L is a cleavable or non-cleavable linker; And

CTX is a cytotoxin linked to an L amide bond, a carbamate bond, a disulfide bond, an ether bond, a thioether bond, or an ester bond.

For example, antibody-drug conjugates of formula (Ic2) are prepared using anti-C10orf54 antibodies (eg, humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate of formula (IIb) or (IIc), where CTX is MMAF and L is -(CH ₂ ) ₅ C(O)-.

For example, antibody-drug conjugates of formula (Ic2) are prepared using anti-C10orf54 antibodies (e.g., humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate that has one of the following structures:

And

For example, antibody-drug conjugates of formula (Ic2) are prepared using anti-C10orf54 antibodies (eg, humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate of formula (IIb) or (IIc), where CTX is MMAE and L is -(CH ₂ ) ₅ C(O)-Val-Ala-RAV-O-C(O)- or -(CH ₂ ) ₅ C(O)-Val-Cit-PAB-OC(O)-.

For example, antibody-drug conjugates of formula (Ic2) are prepared using anti-C10orf54 antibodies (e.g., humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate that has one of the following structures:

And

For example, antibody-drug conjugates of formula (Ic2) are prepared using anti-C10orf54 antibodies (e.g., humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate of formula (IIb) or (IIc), where CTX is PBD and L is -(CH ₂ ) ₅ C(O)-Val-Ala-, -(CH ₂ ) ₅ C(O)-Val-Cit-, -(CH ₂ ) ₅ C(O)-Val-Ala-PAB-OC (O)- or -(CH ₂ ) ₅ C(O)-Val-Cit-PAB-OC(O)-.

For example, antibody-drug conjugates of formula (Ic2) are prepared using anti-C10orf54 antibodies (e.g., humanized anti-C10orf54 antibodies) using a linker-cytotoxin conjugate that has one of the following structures:

And

The antibody-drug conjugates described in this example and in this specification are prepared where one or more interchain disulfide bonds in the antibody are used for conjugation (eg, four interchain disulfide bonds as depicted above in typical Schemes F and G). Antibody-drug conjugates, where one or more interchain disulfide bonds in the antibody are used for conjugation, as set forth herein, are characterized by a preferred antibody to drug ratio of four.

Cell viability experiments were performed using human AML cell lines such as OCI/AML3, PL21 and P31/FUJ. For primary ADC assays, myeloid cell lines were subcultured in RPMI or minimal maintenance medium (MEM) (LifeTech) supplemented with 10–20% fetal bovine serum (LifeTech), according to established practice. For toxicity assays, cells were seeded in 384-well plates (Greiner) at 3000 cells per well in 50 μl of medium.

For primary ADC assays, serial dilutions of DBM(C6)MMAF-conjugated anti-C10orf54 antibodies were prepared from 100–300 nM solutions in RPMI and added to appropriate wells in duplicate using an iPipette liquid handling device (Apricot Designs). Cell plates were then incubated for three days followed by lysis in Cell-Titer Glo assay reagent (Promega).

For primary ADC assays, luminescence was quantified on a Synergy HT plate reader (BioTek) and the results were plotted. IC ₅₀ values are calculated by fitting a four-parameter sigmoidal curve (GraphPad). The results of typical assays of primary ADCs using three myeloid cell lines are shown as IC ₅₀ (nM) values in Table 41. For example, the ADCs presented in Table 41 were generated by conjugating humanized antibody variants to a linker-toxin conjugate such as DBM-( C6)-MMAF as described in Example 8. The results indicate that both the OCI/AML3 and P31/FUJ cell lines were sensitive to the anti-C10orf54 antibody-based ADC, while the PL21 cell line was less sensitive.

It is intended that the above-described embodiments of the present invention are only exemplary, and those skilled in the art will be aware of, or be able to determine without anything other than routine experimentation, numerous equivalents to the specific techniques set forth herein. All such equivalents are considered to be within the scope of the present invention and are covered by the following claims. In addition, as used in this specification and claims, the singular forms described in the English version by the articles "a," "an" and "the" include the plural forms unless the content clearly dictates otherwise. Thus, for example, reference to “antibody” includes a mixture of two or more such antibodies, and the like. Moreover, those of ordinary skill in the art will recognize that operating sequences must be set out in some particular order for the purpose of explanation and claims, but the present invention contemplates various modifications beyond such particular order.

EXAMPLE 9. FUNCTIONAL ANALYSIS

The following experiments were performed to determine the optimal culture conditions and activation of naïve T cells, provided that this activation could be reversed by administration of antibodies to C10orf54. Once the optimal conditions are determined, they can be used in further screening for antibodies to C10orf54, such as the antibodies described in this application. Optimal concentrations of anti-CD3 antibodies, anti-CD28 antibodies, C10orf54-Fc and T cells were determined.

The CellTiter-Glo luminescent cell viability assay was used to determine the viability of T cells cultured under various conditions. T cell activation was achieved by precoating the plates with anti-CD3 antibodies followed by co-stimulation with anti-CD28 antibodies in solution. Initial conditions were based on data presented in Wang et al., Biofunctions of three new B7 family members, https://www.mdsystems.com (December 10, 2015).

T cell concentration appears to be an important characteristic for anti-CD3/anti-CD28-dependent T cell stimulation. Only at the largest number tested, 50,000 cells per well of a 384-well plate, was this relationship demonstrated and used for all further steps. The minimum concentration of anti-CD3 antibody at which activation close to the maximum level was achieved was 5 μg/ml. At this specific concentration of anti-CD3 antibodies, a concentration-dependent effect of C10orf54-Fc on T cell proliferation was observed. With stronger activation achieved using magnetic beads coated with CD2/CD3/CD28, no such effect was observed.

It was shown that the minimum concentration of anti-CD28 antibody at which T-cell proliferation close to the maximum level was achieved was approximately 3-4 μg/ml. A concentration-dependent effect of C10orf54-Fc on T cell proliferation was observed across the entire range tested for the KCD28 antibody. As a result, a point of 3.2 μg/ml was selected for further stages.

Pan T cells behaved similarly to naïve T cells. However, naive T cells were more sensitive to inhibition by C10orf54-Fc than pan T cells (FIGS. 30A-30C).

Thus, based on the analysis described above, the optimized conditions for culturing and activating naive T cells are: a concentration of 5 μg/ml for anti-CD3 antibodies and 3.2 μg/ml for anti-CD28 antibodies. The moderate level of activation made it possible to eliminate this activation by introducing C10orf54-Fc, making this assay useful for evaluating antibodies to C10orf54.

To determine whether antibodies to C10orf54 enhance T cell stimulation, additional in vitro assays were performed as described below.

Antibodies to C10orf54 described in this application were immobilized on the plate at various concentrations. Naive T cells were stimulated by adding soluble anti-CD28 antibodies at a concentration of 5 μg/ml and contacting naïve T cells with immobilized anti-CD3 antibodies at a concentration of 3.2 μg/ml in the same plate where anti-C10orf54 antibodies were present. Increased T cell stimulation was recorded by IL-2 secretion, interferon-γ (IFN-γ) secretion, and ^3H -thymidine incorporation (an indicator of cell proliferation).

The effect of anti-C10orf54 antibodies on T cell stimulation is summarized in Table 42 below.

In addition, to determine whether antibodies to C10orf54 induce T cell proliferation, in vitro assays were performed as described below.

The C10orf54-Fc construct described above was immobilized on the plate at various concentrations. As a positive control, an IgG-Fc construct was also immobilized on a separate plate. Naive T cells were stimulated by adding soluble anti-CD28 antibodies at a concentration of 5 μg/ml and contacting naive T cells with immobilized anti-CD3 antibodies at a concentration of 3.2 μg/ml in the same plate where either the C10orf54-Fc construct was present , or IgG-Fc as control. In addition, soluble anti-C10orf54 antibodies (26A or 175A, described herein) were added to further enhance T cell stimulation. Increased T cell stimulation was recorded by IL-2 secretion, IFN-γ secretion and ^3H -thymidine incorporation (an indicator of cell proliferation).

Anti-C10orf54 antibody 26A attenuated C10orf54-mediated suppression of naïve T cell proliferation as well as IL-2 and IFN-γ secretion. These results are shown in FIG. 29.

To determine whether C10orf54 inhibits T cell stimulation of naïve T cells, CD4+ T cells, and CD8+ T cells, additional in vitro assays were performed as described below.

The C10orf54-Fc construct described above was immobilized on the plate at various concentrations. As a positive control, an IgG-Fc construct was also immobilized on a separate plate. T cells were stimulated by adding soluble anti-CD28 antibodies at a concentration of 5 μg/ml and contacting the T cells with immobilized anti-CD3 antibodies at a concentration of 3.2 μg/ml in the same plate where either the C10orf54-Fc construct or IgG-Fc as control. Inhibition of T cell stimulation was recorded by the incorporation of ³ H-thymidine (an indicator of cell proliferation).

The immobilized C10orf54-Fc construct at a concentration of 10 μg/ml inhibited anti-CD3/anti-CD28-stimulated naïve T cells and also inhibited CD4+ or CD8+ T cells as measured by ^3H -thymidine incorporation. These results are shown in FIG. 28. In additional assays, anti-C10orf54 antibodies, such as 26A, are added to the assay to attenuate C10orf54-mediated suppression of naïve T cells, CD4 ⁺ T cells, or CD8 ⁺ T cells.

The contents of all references provided herein are hereby incorporated by reference. Other embodiments are presented in the following claims.

--->

SEQUENCE LISTING

<110> Igenica Biotherapeutics, Inc.

<120> ANTI-C10ORF54 ANTIBODIES AND USES THEREOF

<130> 13390-028-228

<140> TBA

<141> 2015-12-11

<150>US 62/090,880

<151> 2014-12-11

<160> 1923

<170> FastSEQ for Windows Version 4.0

<210> 1

<211> 118

<212>PRT

<213> Murine

<220>

<223> Murine antibody 76E1 VH domain

<400> 1

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

1 5 10 15

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

20 25 30

Asn Met Asn Trp Val Lys Gln Ser Asn Gly Lys Ser Leu Glu Trp Ile

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ala Thr Ser Thr Met Ile Thr Pro Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Thr Leu Thr Val Ser Ser

115

<210> 2

<211> 121

<212>PRT

<213> Murine

<220>

<223> Murine antibody 141A VH domain

<400> 2

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr

65 70 75 80

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

85 90 95

Ala Gly Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ala

115 120

<210> 3

<211> 119

<212>PRT

<213> Murine

<220>

<223> Murine antibody 175A VH domain

<400> 3

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr

65 70 75 80

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

85 90 95

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

100 105 110

Thr Ser Val Thr Val Ser Ser

115

<210> 4

<211> 112

<212>PRT

<213> Murine

<220>

<223> Murine antibody 76E1 VL domain

<400> 4

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

1 5 10 15

Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Asn Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly

85 90 95

Ser His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 5

<211> 106

<212>PRT

<213> Murine

<220>

<223> Murine antibody 141A VL domain

<400> 5

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu

65 70 75 80

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

85 90 95

Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 6

<211> 112

<212>PRT

<213> Murine

<220>

<223> Murine antibody 175A VH domain

<400> 6

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

1 5 10 15

Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly

85 90 95

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

100 105 110

<210> 7

<211> 98

<212>PRT

<213> Homo sapiens

<220>

<223> Human germline Immunoglobulin (IMGT IGHV1-18) Heavy chain

<400> 7

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg

<210> 8

<211> 98

<212>PRT

<213> Homo sapiens

<220>

<223> Human germline Immunoglobulin (IMGT IGHV3-48) Heavy chain

<400> 8

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Tyr Ile Ser Ser Ser Ser Ser Thr Ile Tyr Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg

<210> 9

<211> 100

<212>PRT

<213> Homo sapiens

<220>

<223> Human germline Immunoglobulin (IMGT IGKV2-28) light chain

<400> 9

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Leu Gln Thr Pro

100

<210> 10

<211> 95

<212>PRT

<213> Homo sapiens

<220>

<223> Human germline Immunoglobulin (IMGT IGKV1-39) light chain

<400> 10

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

<210> 11

<211> 96

<212>PRT

<213> Homo sapiens

<220>

<223> Human germline Immunoglobulin (IMGT IGKV3-20) light chain

<400> 11

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

<210> 12

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 12

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

Lys Asp Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

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

85 90 95

Ala Arg Ser Thr Met Ile Thr Pro Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 13

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 13

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Ser Thr Met Ile Thr Pro Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 14

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 14

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Asn Leu Lys Phe

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Ser Thr Met Ile Thr Pro Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 15

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 15

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Ser Thr Met Ile Thr Pro Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 16

<211> 121

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 16

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 17

<211> 121

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 17

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 18

<211> 121

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 18

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 19

<211> 121

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 19

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

Ala Arg Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 20

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 20

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 21

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 21

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 22

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 22

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 23

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VH domain

<400> 23

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

1 5 10 15

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

20 25 30

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

35 40 45

Ser Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Ala Asp Ser Val

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 24

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VL domain

<400> 24

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ser His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 25

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VL domain

<400> 25

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Ile Val His Ser

20 25 30

Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Lys Pro Gly Lys Ala

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Ser His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 26

<211> 106

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VL domain

<400> 26

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

1 5 10 15

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

20 25 30

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

35 40 45

Ala Thr Ser Asn Leu Ala Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

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

65 70 75 80

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

85 90 95

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 27

<211> 106

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VL domain

<400> 27

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 28

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VL domain

<400> 28

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

1 5 10 15

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

20 25 30

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

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

<210> 29

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody VL domain

<400> 29

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ser Ser Gln Ser Ile Val His Ser

20 25 30

Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Lys Pro Gly Lys Ala

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

<210> 30

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR1

<400> 30

Gly Tyr Ser Phe Thr Gly Tyr Asn Met Asn

1 5 10

<210> 31

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 31

Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Asn Leu Lys Phe Lys

1 5 10 15

Asp

<210> 32

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR3

<400> 32

Ser Thr Met Ile Thr Pro Phe Asp Tyr

15

<210> 33

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1a VH CDR1

<400> 33

Gly Tyr Thr Phe Ser Arg Tyr Trp Ile Glu

1 5 10

<210> 34

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1a VH CDR2

<400> 34

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

1 5 10 15

Gly

<210> 35

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1a VH CDR3

<400> 35

Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly Tyr

1 5 10

<210> 36

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR1

<400> 36

Gly Tyr Thr Phe Ser Thr His Trp Ile Glu

1 5 10

<210> 37

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR2

<400> 37

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

1 5 10 15

Gly

<210> 38

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR3

<400> 38

Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Tyr

1 5 10

<210> 39

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1a VH FR1

<400> 39

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser

20 25

<210> 40

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVK1 VL CDR2

<400> 40

Lys Val Ser Asn Arg Phe Ser

15

<210> 41

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVK2 VL CDR3

<400> 41

Phe Gln Gly Ser His Val Pro Trp Thr

15

<210> 42

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL CDR1

<400> 42

Arg Ala Ser Ser Ser Leu Ser Tyr Met His

1 5 10

<210> 43

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVK2 VL CDR3

<400> 43

Ala Thr Ser Asn Leu Ala Ser

15

<210> 44

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL CDR3

<400> 44

Gln Gln Trp Ser Ser Asn Pro Tyr Thr

15

<210> 45

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> VL CDR1 of a humanized anti-C10orf54 antibody

<400> 45

Arg Ser Ser Gln Ser Ile Val His Ser Asn Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 46

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VL CDR2

<400> 46

Lys Leu Ser Asn Arg Phe Ser

15

<210> 47

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VL CDR3

<400> 47

Phe Gln Gly Ser His Phe Pro Tyr Thr

15

<210> 48

<400> 48

000

<210> 49

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH CDR2

<400> 49

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

1 5 10 15

Gly

<210> 50

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1b VH CDR2

<400> 50

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

1 5 10 15

Gly

<210> 51

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH FR1

<400> 51

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

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser

20 25

<210> 52

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH FR2

<400> 52

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

1 5 10

<210> 53

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1b VH FR3

<400> 53

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

1 5 10 15

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

20 25 30

<210> 54

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH FR4

<400> 54

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser

1 5 10

<210> 55

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3b VH FR1

<400> 55

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 56

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3a VH FR2

<400> 56

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

1 5 10

<210> 57

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 57

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

1 5 10 15

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

20 25 30

<210> 58

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1a VH FR1

<400> 58

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

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser

20 25

<210> 59

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR1

<400> 59

Gly Tyr Ser Phe Thr Gly Tyr Gln Met Asn

1 5 10

<210> 60

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR1

<400> 60

Gly Tyr Ser Phe Thr Gly Tyr Ser Met Asn

1 5 10

<210> 61

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR1

<400> 61

Gly Tyr Ser Phe Thr Gly Tyr Asp Met Asn

1 5 10

<210> 62

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR1

<400> 62

Gly Tyr Ser Phe Thr Gly Tyr Ala Met Asn

1 5 10

<210> 63

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH FR2

<400> 63

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

1 5 10

<210> 64

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH FR2

<400> 64

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

1 5 10

<210> 65

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 65

Asn Ile Glu Pro Tyr Tyr Asp Tyr Thr Ser Tyr Asn Leu Lys Phe Lys

1 5 10 15

Asp

<210> 66

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 66

Asn Ile Ser Pro Tyr Tyr Asp Tyr Thr Ser Tyr Asn Leu Lys Phe Lys

1 5 10 15

Asp

<210> 67

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 67

Asn Ile Ala Pro Tyr Tyr Asp Tyr Thr Ser Tyr Asn Leu Lys Phe Lys

1 5 10 15

Asp

<210> 68

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 68

Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Gln Leu Lys Phe Lys

1 5 10 15

Asp

<210> 69

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 69

Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ser Leu Lys Phe Lys

1 5 10 15

Asp

<210> 70

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 70

Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Asp Leu Lys Phe Lys

1 5 10 15

Asp

<210> 71

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 71

Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Leu Lys Phe Lys

1 5 10 15

Asp

<210> 72

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 72

Asn Ile Glu Pro Tyr Tyr Asp Tyr Thr Ser Tyr Gln Leu Lys Phe Lys

1 5 10 15

Asp

<210> 73

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 73

Asn Ile Glu Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ser Leu Lys Phe Lys

1 5 10 15

Asp

<210> 74

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 74

Asn Ile Glu Pro Tyr Tyr Asp Tyr Thr Ser Tyr Asp Leu Lys Phe Lys

1 5 10 15

Asp

<210> 75

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL FR1

<400> 75

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

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys

20

<210> 76

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL FR2

<400> 76

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

1 5 10 15

<210> 77

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL FR3

<400> 77

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

1 5 10 15

Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys

20 25 30

<210> 78

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL FR4

<400> 78

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

1 5 10

<210> 79

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR1

<400> 79

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys

20

<210> 80

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR2

<400> 80

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

1 5 10 15

<210> 81

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR3

<400> 81

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

1 5 10 15

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

20 25 30

<210> 82

<211> 15

<212>PRT

<213> Homo sapiens

<220>

<223> Joining region IMGT IGHJ4-01

<400> 82

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

1 5 10 15

<210> 83

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 83

Asn Ile Glu Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Leu Lys Phe Lys

1 5 10 15

Asp

<210> 84

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 84

Asn Ile Ser Pro Tyr Tyr Asp Tyr Thr Ser Tyr Gln Leu Lys Phe Lys

1 5 10 15

Asp

<210> 85

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 85

Asn Ile Ser Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ser Leu Lys Phe Lys

1 5 10 15

Asp

<210> 86

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 86

Asn Ile Ser Pro Tyr Tyr Asp Tyr Thr Ser Tyr Asp Leu Lys Phe Lys

1 5 10 15

Asp

<210> 87

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 87

Asn Ile Ser Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Leu Lys Phe Lys

1 5 10 15

Asp

<210> 88

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 88

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

1 5 10 15

Asp

<210> 89

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 89

Asn Ile Ala Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ser Leu Lys Phe Lys

1 5 10 15

Asp

<210> 90

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 90

Asn Ile Ala Pro Tyr Tyr Asp Tyr Thr Ser Tyr Asp Leu Lys Phe Lys

1 5 10 15

Asp

<210> 91

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR1

<400> 91

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

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys

20

<210> 92

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR2

<400> 92

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

1 5 10 15

<210> 93

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR3

<400> 93

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

1 5 10 15

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

20 25 30

<210> 94

<211> 12

<212>PRT

<213> Homo sapiens

<220>

<223> Joining region IMGT IGKJ2-01

<400> 94

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

1 5 10

<210> 95

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH CDR2

<400> 95

Asn Ile Ala Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Leu Lys Phe Lys

1 5 10 15

Asp

<210> 96

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH FR3

<400> 96

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

1 5 10 15

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

20 25 30

<210> 97

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH FR3

<400> 97

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

1 5 10 15

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

20 25 30

<210> 98

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1a VH FR3

<400> 98

Arg Val Thr Met Thr Thr Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 99

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3b VH CDR2

<400> 99

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

1 5 10 15

Gly

<210> 100

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3b VH CDR2

<400> 100

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

1 5 10 15

Gly

<210> 101

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1a VH CDR2

<400> 101

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

1 5 10 15

Gly

<210> 102

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1a VH CDR2

<400> 102

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

1 5 10 15

Gly

<210> 103

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1a VH CDR2

<400> 103

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

1 5 10 15

Gly

<210> 104

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1a VH CDR2

<400> 104

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

1 5 10 15

Gly

<210> 105

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1a VH FR1

<400> 105

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

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser

20 25

<210> 106

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1a VH FR2

<400> 106

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

1 5 10

<210> 107

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1 VH FR3

<400> 107

Arg Ala Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 108

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1 VH FR3

<400> 108

Arg Val Thr Phe Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 109

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1 VH FR3

<400> 109

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

1 5 10 15

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

20 25 30

<210> 110

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1 VH FR3

<400> 110

Arg Ala Thr Phe Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 111

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1 VH FR3

<400> 111

Arg Val Thr Phe Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 112

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1 VH FR3

<400> 112

Arg Ala Thr Met Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 113

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1 VH FR3

<400> 113

Arg Ala Thr Phe Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 114

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH1b VH CDR2

<400> 114

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

1 5 10 15

Gly

<210> 115

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3a VH FR1

<400> 115

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

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 116

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3a VH FR1

<400> 116

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

1 5 10 15

Ser Val Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 117

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3a VH FR1

<400> 117

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

1 5 10 15

Ser Leu Arg Ile Ser Cys Ala Ala Ser

20 25

<210> 118

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3a VH FR1

<400> 118

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

1 5 10 15

Ser Val Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 119

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3a VH FR1

<400> 119

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

1 5 10 15

Ser Val Arg Ile Ser Cys Ala Ala Ser

20 25

<210> 120

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3a VH FR1

<400> 120

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

1 5 10 15

Ser Leu Arg Ile Ser Cys Ala Ala Ser

20 25

<210> 121

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3a VH FR1

<400> 121

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

1 5 10 15

Ser Val Arg Ile Ser Cys Ala Ala Ser

20 25

<210> 122

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3a VH FR2

<400> 122

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

1 5 10

<210> 123

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3a VH FR2

<400> 123

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

1 5 10

<210> 124

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3a VH FR2

<400> 124

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

1 5 10

<210> 125

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 125

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

1 5 10 15

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

20 25 30

<210> 126

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 126

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 127

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 127

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

1 5 10 15

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

20 25 30

<210> 128

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 128

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

1 5 10 15

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

20 25 30

<210> 129

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 129

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

1 5 10 15

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

20 25 30

<210> 130

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 130

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

1 5 10 15

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

20 25 30

<210> 131

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 131

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

1 5 10 15

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

20 25 30

<210> 132

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 132

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 133

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 133

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

1 5 10 15

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

20 25 30

<210> 134

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 134

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

1 5 10 15

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

20 25 30

<210> 135

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 135

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

1 5 10 15

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

20 25 30

<210> 136

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 136

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

1 5 10 15

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

20 25 30

<210> 137

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 137

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

1 5 10 15

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

20 25 30

<210> 138

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 138

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 139

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 139

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 140

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 140

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 141

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 141

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 142

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 142

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 143

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 143

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

1 5 10 15

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

20 25 30

<210> 144

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 144

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

1 5 10 15

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

20 25 30

<210> 145

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 145

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

1 5 10 15

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

20 25 30

<210> 146

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 146

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

1 5 10 15

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

20 25 30

<210> 147

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 147

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

1 5 10 15

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

20 25 30

<210> 148

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 148

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

1 5 10 15

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

20 25 30

<210> 149

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 149

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

1 5 10 15

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

20 25 30

<210> 150

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 150

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 151

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 151

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

1 5 10 15

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

20 25 30

<210> 152

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 152

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

1 5 10 15

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

20 25 30

<210> 153

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 153

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 154

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 154

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 155

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 155

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 156

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 156

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 157

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 157

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 158

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 158

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

1 5 10 15

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

20 25 30

<210> 159

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 159

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

1 5 10 15

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

20 25 30

<210> 160

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 160

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

1 5 10 15

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

20 25 30

<210> 161

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 161

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

1 5 10 15

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

20 25 30

<210> 162

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 162

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

1 5 10 15

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

20 25 30

<210> 163

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 163

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

1 5 10 15

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

20 25 30

<210> 164

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 164

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

1 5 10 15

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

20 25 30

<210> 165

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 165

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

1 5 10 15

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

20 25 30

<210> 166

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 166

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

1 5 10 15

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

20 25 30

<210> 167

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 167

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

1 5 10 15

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

20 25 30

<210> 168

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 168

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 169

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 169

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 170

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 170

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 171

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 171

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 172

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 172

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 173

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 173

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 174

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 174

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 175

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 175

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 176

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 176

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 177

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 177

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 178

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 178

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

1 5 10 15

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

20 25 30

<210> 179

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 179

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

1 5 10 15

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

20 25 30

<210> 180

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 180

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

1 5 10 15

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

20 25 30

<210> 181

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 181

Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 182

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 182

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

1 5 10 15

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

20 25 30

<210> 183

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 183

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

1 5 10 15

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

20 25 30

<210> 184

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 184

Arg Phe Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 185

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 185

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

1 5 10 15

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

20 25 30

<210> 186

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 186

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

1 5 10 15

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

20 25 30

<210> 187

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 187

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 188

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 188

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 189

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 189

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 190

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 190

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 191

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 191

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 192

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 192

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 193

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 193

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 194

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 194

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 195

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 195

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 196

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 196

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 197

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 197

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 198

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 198

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

1 5 10 15

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

20 25 30

<210> 199

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 199

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

1 5 10 15

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

20 25 30

<210> 200

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 200

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

1 5 10 15

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

20 25 30

<210> 201

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 201

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

1 5 10 15

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

20 25 30

<210> 202

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 202

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

1 5 10 15

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

20 25 30

<210> 203

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 203

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

1 5 10 15

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

20 25 30

<210> 204

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 204

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

1 5 10 15

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

20 25 30

<210> 205

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 205

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

1 5 10 15

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

20 25 30

<210> 206

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 206

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

1 5 10 15

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

20 25 30

<210> 207

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 207

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

1 5 10 15

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

20 25 30

<210> 208

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 208

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 209

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 209

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 210

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 210

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 211

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 211

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 212

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 212

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 213

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 213

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 214

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 214

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 215

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 215

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 216

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 216

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 217

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 217

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 218

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 218

Arg Phe Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 219

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 219

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

1 5 10 15

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

20 25 30

<210> 220

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 220

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

1 5 10 15

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

20 25 30

<210> 221

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 221

Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 222

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 222

Arg Phe Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 223

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 223

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 224

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 224

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 225

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 225

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 226

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 226

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 227

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 227

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 228

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 228

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 229

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 229

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 230

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 230

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 231

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 231

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 232

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 232

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 233

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 233

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

1 5 10 15

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

20 25 30

<210> 234

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 234

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

1 5 10 15

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

20 25 30

<210> 235

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 235

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

1 5 10 15

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

20 25 30

<210> 236

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 236

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

1 5 10 15

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

20 25 30

<210> 237

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 237

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

1 5 10 15

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

20 25 30

<210> 238

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 238

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 239

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 239

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 240

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 240

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 241

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 241

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 242

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 242

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 243

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 243

Arg Phe Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 244

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 244

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 245

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 245

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 246

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 246

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 247

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 247

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 248

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 248

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 249

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 249

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

1 5 10 15

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

20 25 30

<210> 250

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 250

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 251

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVH3 VH FR3

<400> 251

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 252

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL FR1

<400> 252

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

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys

20

<210> 253

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 253

Arg Ser Ser Gln Ser Ile Val His Ser Gln Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 254

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 254

Arg Ser Ser Gln Ser Ile Val His Ser Ser Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 255

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 255

Arg Ser Ser Gln Ser Ile Val His Ser Ala Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 256

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 256

Arg Ser Ser Gln Ser Ile Val His Ser Asn Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 257

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 257

Arg Ser Ser Gln Ser Ile Val His Ser Asn Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 258

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 258

Arg Ser Ser Gln Ser Ile Val His Ser Asn Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 259

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 259

Arg Ser Ser Gln Ser Ile Val His Ser Asn Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 260

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 260

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

1 5 10 15

<210> 261

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 261

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

1 5 10 15

<210> 262

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 262

Arg Ser Ser Gln Ser Ile Val His Ser Gln Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 263

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 263

Arg Ser Ser Gln Ser Ile Val His Ser Gln Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 264

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 264

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

1 5 10 15

<210> 265

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 265

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

1 5 10 15

<210> 266

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 266

Arg Ser Ser Gln Ser Ile Val His Ser Ser Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 267

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 267

Arg Ser Ser Gln Ser Ile Val His Ser Ser Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 268

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 268

Arg Ser Ser Gln Ser Ile Val His Ser Ala Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 269

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 269

Arg Ser Ser Gln Ser Ile Val His Ser Ala Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 270

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 270

Arg Ser Ser Gln Ser Ile Val His Ser Ala Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 271

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR1

<400> 271

Arg Ser Ser Gln Ser Ile Val His Ser Ala Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 272

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR2

<400> 272

Lys Leu Ser Gln Arg Phe Ser

15

<210> 273

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR2

<400> 273

Lys Leu Ser Ser Arg Phe Ser

15

<210> 274

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR2

<400> 274

Lys Leu Ser Ala Arg Phe Ser

15

<210> 275

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL CDR2

<400> 275

Lys Leu Ser Asp Arg Phe Ser

15

<210> 276

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK2 VL FR3

<400> 276

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

1 5 10 15

Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys

20 25 30

<210> 277

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR1

<400> 277

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys

20

<210> 278

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR1

<400> 278

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys

20

<210> 279

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR1

<400> 279

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

1 5 10 15

Asp Arg Ala Thr Ile Thr Cys

20

<210> 280

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR1

<400> 280

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

1 5 10 15

Asp Arg Val Thr Ile Thr Cys

20

<210> 281

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR1

<400> 281

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

1 5 10 15

Asp Arg Ala Thr Ile Thr Cys

20

<210> 282

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR1

<400> 282

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

1 5 10 15

Asp Arg Ala Thr Ile Thr Cys

20

<210> 283

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR1

<400> 283

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

1 5 10 15

Asp Arg Ala Thr Ile Thr Cys

20

<210> 284

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR2

<400> 284

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

1 5 10 15

<210> 285

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR3

<400> 285

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

1 5 10 15

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

20 25 30

<210> 286

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR3

<400> 286

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

1 5 10 15

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

20 25 30

<210> 287

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR3

<400> 287

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

1 5 10 15

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

20 25 30

<210> 288

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR3

<400> 288

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

1 5 10 15

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

20 25 30

<210> 289

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR3

<400> 289

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

1 5 10 15

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

20 25 30

<210> 290

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR3

<400> 290

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

1 5 10 15

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

20 25 30

<210> 291

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A-huVK1 VL FR3

<400> 291

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

1 5 10 15

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

20 25 30

<210> 292

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 292

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

1 5 10 15

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

20 25 30

<210> 293

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 293

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

1 5 10 15

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

20 25 30

<210> 294

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 294

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

1 5 10 15

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

20 25 30

<210> 295

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 295

Arg Ala Thr Met Thr Thr Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 296

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 296

Arg Ala Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 297

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 297

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

1 5 10 15

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

20 25 30

<210> 298

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 298

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

1 5 10 15

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

20 25 30

<210> 299

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 299

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

1 5 10 15

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

20 25 30

<210> 300

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 300

Arg Val Thr Met Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 301

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 301

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

1 5 10 15

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

20 25 30

<210> 302

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 302

Arg Val Thr Met Thr Thr Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 303

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 303

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

1 5 10 15

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

20 25 30

<210> 304

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 304

Arg Ala Thr Leu Thr Thr Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 305

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 305

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

1 5 10 15

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

20 25 30

<210> 306

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 306

Arg Ala Thr Met Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 307

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 307

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

1 5 10 15

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

20 25 30

<210> 308

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 308

Arg Ala Thr Met Thr Thr Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 309

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 309

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

1 5 10 15

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

20 25 30

<210> 310

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 310

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

1 5 10 15

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

20 25 30

<210> 311

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 311

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

1 5 10 15

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

20 25 30

<210> 312

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 312

Arg Val Thr Met Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 313

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 313

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

1 5 10 15

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

20 25 30

<210> 314

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 314

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

1 5 10 15

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

20 25 30

<210> 315

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 315

Arg Ala Thr Leu Thr Thr Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 316

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 316

Arg Ala Thr Met Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

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

20 25 30

<210> 317

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 317

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

1 5 10 15

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

20 25 30

<210> 318

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1 VH FR3

<400> 318

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

1 5 10 15

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

20 25 30

<210> 319

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1b VH CDR3

<400> 319

Ser Thr Leu Ile Thr Pro Phe Asp Tyr

15

<210> 320

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1b VH FR4

<400> 320

Trp Gly Gln Gly Thr Leu Leu Thr Val Ser Ser

1 5 10

<210> 321

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1b VH CDR2

<400> 321

Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Gln Lys Leu Gln

1 5 10 15

Gly

<210> 322

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH1b VH CDR2

<400> 322

Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Gln Lys Phe Gln

1 5 10 15

Gly

<210> 323

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR2

<400> 323

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

1 5 10

<210> 324

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR2

<400> 324

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

1 5 10

<210> 325

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR2

<400> 325

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

1 5 10

<210> 326

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR2

<400> 326

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

1 5 10

<210> 327

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 327

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

1 5 10 15

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

20 25 30

<210> 328

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 328

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 329

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 329

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

1 5 10 15

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

20 25 30

<210> 330

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 330

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

1 5 10 15

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

20 25 30

<210> 331

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 331

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

1 5 10 15

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

20 25 30

<210> 332

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 332

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

1 5 10 15

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

20 25 30

<210> 333

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 333

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

1 5 10 15

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

20 25 30

<210> 334

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 334

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

1 5 10 15

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

20 25 30

<210> 335

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 335

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

1 5 10 15

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

20 25 30

<210> 336

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 336

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 337

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 337

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

1 5 10 15

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

20 25 30

<210> 338

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 338

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

1 5 10 15

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

20 25 30

<210> 339

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 339

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

1 5 10 15

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

20 25 30

<210> 340

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 340

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

1 5 10 15

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

20 25 30

<210> 341

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 341

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

1 5 10 15

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

20 25 30

<210> 342

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 342

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

1 5 10 15

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

20 25 30

<210> 343

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 343

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

1 5 10 15

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

20 25 30

<210> 344

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 344

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 345

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 345

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 346

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 346

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 347

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 347

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 348

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 348

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 349

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 349

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 350

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 350

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 351

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 351

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

1 5 10 15

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

20 25 30

<210> 352

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 352

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

1 5 10 15

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

20 25 30

<210> 353

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 353

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

1 5 10 15

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

20 25 30

<210> 354

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 354

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 355

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 355

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

1 5 10 15

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

20 25 30

<210> 356

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 356

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

1 5 10 15

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

20 25 30

<210> 357

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 357

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 358

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 358

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

1 5 10 15

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

20 25 30

<210> 359

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 359

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

1 5 10 15

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

20 25 30

<210> 360

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 360

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

1 5 10 15

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

20 25 30

<210> 361

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 361

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

1 5 10 15

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

20 25 30

<210> 362

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 362

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

1 5 10 15

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

20 25 30

<210> 363

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 363

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

1 5 10 15

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

20 25 30

<210> 364

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 364

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

1 5 10 15

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

20 25 30

<210> 365

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 365

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

1 5 10 15

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

20 25 30

<210> 366

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 366

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 367

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 367

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

1 5 10 15

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

20 25 30

<210> 368

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 368

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

1 5 10 15

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

20 25 30

<210> 369

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 369

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

1 5 10 15

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

20 25 30

<210> 370

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 370

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

1 5 10 15

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

20 25 30

<210> 371

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 371

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

1 5 10 15

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

20 25 30

<210> 372

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 372

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

1 5 10 15

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

20 25 30

<210> 373

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 373

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 374

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 374

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 375

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 375

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 376

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 376

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

1 5 10 15

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

20 25 30

<210> 377

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 377

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 378

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 378

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 379

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 379

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

1 5 10 15

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

20 25 30

<210> 380

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 380

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

1 5 10 15

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

20 25 30

<210> 381

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 381

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

1 5 10 15

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

20 25 30

<210> 382

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 382

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

1 5 10 15

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

20 25 30

<210> 383

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 383

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

1 5 10 15

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

20 25 30

<210> 384

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 384

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

1 5 10 15

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

20 25 30

<210> 385

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 385

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 386

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 386

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

1 5 10 15

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

20 25 30

<210> 387

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 387

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

1 5 10 15

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

20 25 30

<210> 388

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 388

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

1 5 10 15

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

20 25 30

<210> 389

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 389

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

1 5 10 15

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

20 25 30

<210> 390

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 390

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

1 5 10 15

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

20 25 30

<210> 391

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 391

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

1 5 10 15

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

20 25 30

<210> 392

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 392

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

1 5 10 15

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

20 25 30

<210> 393

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 393

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

1 5 10 15

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

20 25 30

<210> 394

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 394

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

1 5 10 15

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

20 25 30

<210> 395

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 395

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

1 5 10 15

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

20 25 30

<210> 396

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 396

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

1 5 10 15

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

20 25 30

<210> 397

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 397

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

1 5 10 15

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

20 25 30

<210> 398

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 398

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

1 5 10 15

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

20 25 30

<210> 399

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 399

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

1 5 10 15

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

20 25 30

<210> 400

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 400

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 401

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 401

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 402

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 402

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 403

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 403

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 404

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 404

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 405

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 405

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 406

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 406

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 407

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 407

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 408

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 408

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 409

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 409

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 410

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 410

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 411

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 411

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 412

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 412

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 413

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 413

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 414

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 414

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 415

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 415

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 416

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 416

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 417

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 417

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 418

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 418

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 419

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 419

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 420

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 420

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 421

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 421

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

1 5 10 15

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

20 25 30

<210> 422

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 422

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

1 5 10 15

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

20 25 30

<210> 423

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 423

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 424

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 424

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

1 5 10 15

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

20 25 30

<210> 425

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 425

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

1 5 10 15

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

20 25 30

<210> 426

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 426

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

1 5 10 15

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

20 25 30

<210> 427

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 427

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 428

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 428

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

1 5 10 15

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

20 25 30

<210> 429

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 429

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

1 5 10 15

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

20 25 30

<210> 430

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 430

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

1 5 10 15

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

20 25 30

<210> 431

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 431

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

1 5 10 15

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

20 25 30

<210> 432

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 432

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

1 5 10 15

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

20 25 30

<210> 433

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 433

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 434

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 434

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 435

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 435

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

1 5 10 15

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

20 25 30

<210> 436

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 436

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 437

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 437

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 438

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 438

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 439

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 439

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 440

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 440

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 441

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 441

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

1 5 10 15

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

20 25 30

<210> 442

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 442

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

1 5 10 15

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

20 25 30

<210> 443

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 443

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

1 5 10 15

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

20 25 30

<210> 444

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 444

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

1 5 10 15

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

20 25 30

<210> 445

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 445

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

1 5 10 15

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

20 25 30

<210> 446

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 446

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 447

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 447

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

1 5 10 15

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

20 25 30

<210> 448

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 448

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

1 5 10 15

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

20 25 30

<210> 449

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 449

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

1 5 10 15

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

20 25 30

<210> 450

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 450

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

1 5 10 15

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

20 25 30

<210> 451

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 451

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

1 5 10 15

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

20 25 30

<210> 452

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 452

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 453

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 453

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 454

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 454

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

1 5 10 15

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

20 25 30

<210> 455

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 455

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

1 5 10 15

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

20 25 30

<210> 456

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 456

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

1 5 10 15

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

20 25 30

<210> 457

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 457

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

1 5 10 15

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

20 25 30

<210> 458

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 458

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

1 5 10 15

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

20 25 30

<210> 459

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 459

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

1 5 10 15

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

20 25 30

<210> 460

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 460

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

1 5 10 15

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

20 25 30

<210> 461

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 461

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

1 5 10 15

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

20 25 30

<210> 462

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 462

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 463

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 463

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 464

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 464

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

1 5 10 15

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

20 25 30

<210> 465

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 465

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 466

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 466

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 467

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 467

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 468

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 468

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

1 5 10 15

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

20 25 30

<210> 469

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 469

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 470

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 470

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 471

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 471

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

1 5 10 15

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

20 25 30

<210> 472

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 472

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 473

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 473

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 474

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 474

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

1 5 10 15

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

20 25 30

<210> 475

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 475

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

1 5 10 15

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

20 25 30

<210> 476

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 476

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 477

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 477

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

1 5 10 15

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

20 25 30

<210> 478

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 478

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

1 5 10 15

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

20 25 30

<210> 479

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 479

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

1 5 10 15

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

20 25 30

<210> 480

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 480

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

1 5 10 15

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

20 25 30

<210> 481

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 481

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

1 5 10 15

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

20 25 30

<210> 482

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 482

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

1 5 10 15

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

20 25 30

<210> 483

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 483

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

1 5 10 15

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

20 25 30

<210> 484

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 484

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

1 5 10 15

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

20 25 30

<210> 485

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 485

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

1 5 10 15

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

20 25 30

<210> 486

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 486

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 487

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 487

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

1 5 10 15

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

20 25 30

<210> 488

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 488

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

1 5 10 15

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

20 25 30

<210> 489

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 489

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

1 5 10 15

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

20 25 30

<210> 490

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 490

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

1 5 10 15

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

20 25 30

<210> 491

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 491

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

1 5 10 15

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

20 25 30

<210> 492

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 492

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 493

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 493

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

1 5 10 15

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

20 25 30

<210> 494

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 494

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 495

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 495

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 496

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 496

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

1 5 10 15

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

20 25 30

<210> 497

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 497

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

1 5 10 15

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

20 25 30

<210> 498

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 498

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

1 5 10 15

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

20 25 30

<210> 499

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 499

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

1 5 10 15

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

20 25 30

<210> 500

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 500

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

1 5 10 15

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

20 25 30

<210> 501

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 501

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

1 5 10 15

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

20 25 30

<210> 502

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 502

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

1 5 10 15

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

20 25 30

<210> 503

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 503

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

1 5 10 15

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

20 25 30

<210> 504

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 504

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

1 5 10 15

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

20 25 30

<210> 505

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 505

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

1 5 10 15

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

20 25 30

<210> 506

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 506

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

1 5 10 15

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

20 25 30

<210> 507

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 507

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

1 5 10 15

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

20 25 30

<210> 508

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 508

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

1 5 10 15

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

20 25 30

<210> 509

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 509

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

1 5 10 15

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

20 25 30

<210> 510

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 510

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

1 5 10 15

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

20 25 30

<210> 511

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 511

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

1 5 10 15

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

20 25 30

<210> 512

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 512

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 513

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 513

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 514

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 514

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 515

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 515

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 516

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 516

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 517

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 517

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 518

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 518

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 519

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 519

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 520

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 520

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 521

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 521

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

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

20 25 30

<210> 522

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 522

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 523

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 523

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

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

20 25 30

<210> 524

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 524

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 525

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 525

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 526

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 526

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 527

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 527

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 528

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 528

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 529

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 529

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 530

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 530

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 531

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 531

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 532

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 532

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 533

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 533

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 534

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 534

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 535

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 535

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 536

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 536

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 537

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 537

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 538

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 538

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 539

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 539

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 540

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 540

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 541

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 541

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 542

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 542

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 543

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 543

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 544

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 544

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 545

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 545

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 546

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 546

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 547

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 547

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 548

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 548

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 549

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 549

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 550

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 550

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 551

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 551

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 552

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 552

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 553

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 553

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 554

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 554

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 555

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 555

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 556

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 556

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 557

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 557

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 558

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 558

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 559

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 559

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 560

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 560

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 561

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 561

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 562

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 562

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 563

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 563

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 564

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 564

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 565

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 565

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 566

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 566

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 567

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 567

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 568

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 568

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 569

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 569

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 570

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 570

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 571

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 571

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 572

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 572

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 573

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 573

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 574

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 574

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 575

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 575

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 576

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 576

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 577

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 577

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 578

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 578

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 579

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 579

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 580

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 580

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 581

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 581

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 582

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 582

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 583

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 583

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 584

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 584

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 585

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 585

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 586

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 586

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 587

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 587

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 588

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 588

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 589

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 589

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 590

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 590

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 591

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 591

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 592

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 592

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 593

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 593

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 594

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 594

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 595

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 595

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 596

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 596

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 597

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 597

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 598

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 598

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 599

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 599

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 600

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 600

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 601

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 601

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 602

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 602

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 603

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 603

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 604

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 604

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 605

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 605

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 606

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 606

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 607

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 607

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 608

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 608

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 609

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 609

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 610

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 610

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 611

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 611

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 612

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 612

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 613

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 613

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 614

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 614

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 615

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 615

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 616

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 616

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 617

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 617

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 618

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 618

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 619

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 619

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 620

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 620

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 621

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 621

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 622

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 622

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 623

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 623

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 624

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 624

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 625

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 625

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 626

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 626

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 627

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 627

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 628

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 628

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 629

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 629

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 630

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 630

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 631

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 631

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 632

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 632

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 633

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 633

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 634

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 634

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 635

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 635

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 636

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 636

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 637

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 637

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 638

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 638

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 639

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 639

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 640

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 640

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 641

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 641

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 642

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 642

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 643

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 643

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 644

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 644

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 645

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 645

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 646

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 646

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 647

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 647

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 648

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 648

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 649

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 649

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 650

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 650

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 651

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 651

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 652

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 652

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 653

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 653

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 654

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 654

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 655

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 655

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 656

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 656

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 657

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 657

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 658

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 658

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 659

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 659

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 660

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 660

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 661

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 661

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 662

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 662

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 663

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 663

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 664

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 664

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 665

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 665

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 666

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 666

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 667

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 667

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 668

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 668

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 669

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 669

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 670

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 670

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 671

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 671

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 672

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 672

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 673

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 673

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 674

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 674

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 675

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 675

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 676

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 676

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 677

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 677

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 678

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 678

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 679

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 679

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 680

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 680

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 681

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 681

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 682

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 682

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 683

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 683

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 684

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 684

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 685

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 685

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 686

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 686

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 687

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 687

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 688

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 688

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 689

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 689

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 690

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 690

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 691

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 691

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 692

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 692

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 693

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 693

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 694

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 694

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 695

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 695

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 696

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 696

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 697

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 697

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 698

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 698

Arg Phe Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 699

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 699

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 700

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 700

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 701

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 701

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 702

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 702

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 703

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 703

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 704

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 704

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 705

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 705

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 706

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 706

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 707

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 707

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 708

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 708

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 709

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 709

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 710

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 710

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 711

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 711

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 712

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 712

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 713

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 713

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 714

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 714

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 715

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 715

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 716

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 716

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 717

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 717

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 718

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 718

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 719

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 719

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 720

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 720

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 721

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 721

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 722

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 722

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 723

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 723

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 724

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 724

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 725

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 725

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 726

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 726

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 727

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 727

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 728

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 728

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 729

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 729

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 730

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 730

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 731

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 731

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 732

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 732

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 733

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 733

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 734

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 734

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 735

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 735

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 736

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 736

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 737

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 737

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 738

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 738

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 739

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 739

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 740

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 740

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 741

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 741

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 742

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 742

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 743

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 743

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 744

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 744

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 745

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 745

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 746

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 746

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 747

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 747

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 748

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 748

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 749

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 749

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 750

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 750

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 751

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 751

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 752

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 752

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 753

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 753

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 754

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 754

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 755

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 755

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 756

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 756

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 757

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 757

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 758

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 758

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 759

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 759

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 760

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 760

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 761

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 761

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 762

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 762

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 763

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 763

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 764

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 764

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 765

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 765

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 766

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 766

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 767

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 767

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 768

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 768

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 769

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 769

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 770

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 770

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 771

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 771

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 772

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 772

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 773

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 773

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 774

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 774

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 775

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 775

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 776

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 776

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 777

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 777

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 778

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 778

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 779

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 779

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 780

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 780

Arg Phe Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 781

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 781

Arg Phe Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 782

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 782

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 783

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 783

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 784

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 784

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 785

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 785

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 786

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 786

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 787

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 787

Arg Phe Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 788

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 788

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 789

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 789

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 790

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 790

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 791

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 791

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 792

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 792

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 793

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 793

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 794

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 794

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 795

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 795

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 796

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 796

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 797

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 797

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 798

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 798

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 799

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 799

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 800

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 800

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 801

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 801

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 802

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 802

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 803

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 803

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 804

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 804

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 805

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 805

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 806

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 806

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 807

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 807

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 808

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 808

Arg Ala Thr Leu Ser Arg Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 809

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 809

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 810

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 810

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 811

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 811

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 812

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 812

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 813

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 813

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 814

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 814

Arg Ala Thr Ile Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 815

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 815

Arg Ala Thr Ile Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 816

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 816

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 817

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 817

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 818

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 818

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 819

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 819

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 820

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 820

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 821

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 821

Arg Phe Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 822

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 822

Arg Phe Thr Leu Ser Arg Asp Lys Ala Ser Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 823

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 823

Arg Phe Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 824

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 824

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 825

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 825

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 826

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 826

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 827

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 827

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 828

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 828

Arg Ala Thr Leu Ser Val Asp Lys Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 829

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 829

Arg Ala Thr Leu Ser Val Asp Asn Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 830

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 830

Arg Ala Thr Leu Ser Arg Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 831

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 831

Arg Ala Thr Ile Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 832

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 832

Arg Phe Thr Leu Ser Val Asp Lys Ala Lys Ser Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 833

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH FR3

<400> 833

Arg Ala Thr Leu Ser Val Asp Lys Ala Ser Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr

20 25 30

<210> 834

<400> 834

000

<210> 835

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH CDR2

<400> 835

Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 836

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH CDR2

<400> 836

Asn Ile Glu Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 837

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH CDR2

<400> 837

Asn Ile Ser Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 838

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH CDR2

<400> 838

Asn Ile Ala Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 839

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH CDR2

<400> 839

Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 840

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH CDR2

<400> 840

Asn Ile Glu Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 841

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH CDR2

<400> 841

Asn Ile Ser Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 842

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVH3 VH CDR2

<400> 842

Asn Ile Ala Pro Tyr Tyr Asp Tyr Thr Ser Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 843

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVK2 VL CDR2

<400> 843

Lys Val Ser Gln Arg Phe Ser

15

<210> 844

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVK2 VL CDR2

<400> 844

Lys Val Ser Ser Arg Phe Ser

15

<210> 845

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVK2 VL CDR2

<400> 845

Lys Val Ser Asp Arg Phe Ser

15

<210> 846

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1-huVK2 VL CDR2

<400> 846

Lys Val Ser Ala Arg Phe Ser

15

<210> 847

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 847

Glu Ile Leu Pro Gly Ser Gly Ser Thr Gln Tyr Asn Glu Lys Phe Lys

1 5 10 15

Gly

<210> 848

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 848

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Asn Glu Lys Phe Lys

1 5 10 15

Gly

<210> 849

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 849

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asp Tyr Asn Glu Lys Phe Lys

1 5 10 15

Gly

<210> 850

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 850

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ala Tyr Asn Glu Lys Phe Lys

1 5 10 15

Gly

<210> 851

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 851

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Gln Glu Lys Phe Lys

1 5 10 15

Gly

<210> 852

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 852

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Ser Glu Lys Phe Lys

1 5 10 15

Gly

<210> 853

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 853

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Asp Glu Lys Phe Lys

1 5 10 15

Gly

<210> 854

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 854

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Ala Glu Lys Phe Lys

1 5 10 15

Gly

<210> 855

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 855

Glu Ile Leu Pro Gly Ser Gly Ser Thr Gln Tyr Gln Glu Lys Phe Lys

1 5 10 15

Gly

<210> 856

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 856

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Ser Glu Lys Phe Lys

1 5 10 15

Gly

<210> 857

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 857

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asp Tyr Asp Glu Lys Phe Lys

1 5 10 15

Gly

<210> 858

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3a VH CDR2

<400> 858

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ala Tyr Ala Glu Lys Phe Lys

1 5 10 15

Gly

<210> 859

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 859

Arg Val Thr Met Thr Thr Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 860

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 860

Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 861

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 861

Arg Ala Thr Met Thr Thr Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 862

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 862

Arg Ala Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 863

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 863

Arg Val Thr Phe Thr Thr Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 864

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 864

Arg Val Thr Phe Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 865

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 865

Arg Val Thr Met Thr Ala Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 866

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 866

Arg Val Thr Met Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 867

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 867

Arg Val Thr Met Thr Thr Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 868

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 868

Arg Ala Thr Phe Thr Thr Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 869

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 869

Arg Ala Thr Phe Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 870

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 870

Arg Ala Thr Met Thr Ala Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 871

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 871

Arg Ala Thr Met Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 872

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 872

Arg Ala Thr Met Thr Thr Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 873

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 873

Arg Val Thr Phe Thr Ala Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 874

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 874

Arg Val Thr Phe Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 875

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 875

Arg Val Thr Phe Thr Thr Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 876

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 876

Arg Val Thr Met Thr Ala Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 877

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 877

Arg Ala Thr Phe Thr Ala Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg

20 25 30

<210> 878

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 878

Arg Ala Thr Phe Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 879

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 879

Arg Ala Thr Phe Thr Thr Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 880

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 880

Arg Ala Thr Met Thr Ala Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 881

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 881

Arg Val Thr Phe Thr Ala Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 882

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1 VH FR3

<400> 882

Arg Ala Thr Phe Thr Ala Asp Thr Asn Thr Ser Thr Ala Tyr Met Glu

1 5 10 15

Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 883

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH CDR3

<400> 883

Glu Glu Val Tyr Glu Gly Tyr Pro Trp Phe Gly Tyr

1 5 10

<210> 884

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH CDR3

<400> 884

Glu Glu Val Tyr Ser Gly Tyr Pro Trp Phe Gly Tyr

1 5 10

<210> 885

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH CDR3

<400> 885

Glu Glu Val Tyr Ala Gly Tyr Pro Trp Phe Gly Tyr

1 5 10

<210> 886

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH CDR2

<400> 886

Glu Ile Leu Pro Gly Ser Gly Ser Thr Gln Tyr Ala Gln Lys Leu Gln

1 5 10 15

Gly

<210> 887

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH CDR2

<400> 887

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Ala Gln Lys Leu Gln

1 5 10 15

Gly

<210> 888

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH CDR2

<400> 888

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asp Tyr Ala Gln Lys Leu Gln

1 5 10 15

Gly

<210> 889

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH CDR2

<400> 889

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ala Tyr Ala Gln Lys Leu Gln

1 5 10 15

Gly

<210> 890

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH CDR2

<400> 890

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Ala Gln Lys Phe Gln

1 5 10 15

Gly

<210> 891

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH CDR2

<400> 891

Glu Ile Leu Pro Gly Ser Gly Ser Thr Gln Tyr Ala Gln Lys Phe Gln

1 5 10 15

Gly

<210> 892

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH CDR2

<400> 892

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Ala Gln Lys Phe Gln

1 5 10 15

Gly

<210> 893

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH CDR2

<400> 893

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln

1 5 10 15

Gly

<210> 894

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH1b VH CDR2

<400> 894

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ala Tyr Ala Gln Lys Phe Gln

1 5 10 15

Gly

<210> 895

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR1

<400> 895

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Met Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 896

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR1

<400> 896

Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Met Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 897

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR1

<400> 897

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Met Gln Pro Gly Gly

1 5 10 15

Ser Val Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 898

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR1

<400> 898

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Met Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Ile Ser Cys Ala Ala Ser

20 25

<210> 899

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR1

<400> 899

Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Met Gln Pro Gly Gly

1 5 10 15

Ser Val Arg Leu Ser Cys Ala Ala Ser

20 25

<210> 900

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR1

<400> 900

Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Met Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Ile Ser Cys Ala Ala Ser

20 25

<210> 901

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR1

<400> 901

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Met Gln Pro Gly Gly

1 5 10 15

Ser Val Arg Ile Ser Cys Ala Ala Ser

20 25

<210> 902

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR1

<400> 902

Glu Val Gln Leu Val Gln Ser Gly Gly Gly Leu Met Gln Pro Gly Gly

1 5 10 15

Ser Val Arg Ile Ser Cys Ala Ala Ser

20 25

<210> 903

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 903

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 904

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 904

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 905

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 905

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 906

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 906

Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 907

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 907

Arg Phe Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 908

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 908

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 909

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 909

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 910

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 910

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 911

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 911

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 912

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 912

Arg Ala Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 913

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 913

Arg Ala Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 914

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 914

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 915

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 915

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 916

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 916

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 917

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 917

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 918

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 918

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 919

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 919

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 920

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 920

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 921

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 921

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 922

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 922

Arg Phe Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 923

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 923

Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 924

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 924

Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 925

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 925

Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 926

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 926

Arg Phe Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 927

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 927

Arg Phe Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 928

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 928

Arg Phe Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 929

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 929

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 930

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 930

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 931

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 931

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 932

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 932

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 933

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 933

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 934

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 934

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 935

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 935

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 936

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 936

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 937

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 937

Arg Ala Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 938

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 938

Arg Ala Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 939

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 939

Arg Ala Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 940

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 940

Arg Ala Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 941

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 941

Arg Ala Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 942

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 942

Arg Ala Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 943

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 943

Arg Ala Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 944

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 944

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 945

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 945

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 946

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 946

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 947

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 947

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 948

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 948

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 949

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 949

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 950

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 950

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 951

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 951

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 952

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 952

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 953

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 953

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 954

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 954

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 955

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 955

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 956

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 956

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 957

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 957

Arg Phe Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 958

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 958

Arg Phe Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 959

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 959

Arg Phe Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 960

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 960

Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 961

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 961

Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 962

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 962

Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 963

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 963

Arg Phe Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 964

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 964

Arg Phe Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 965

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 965

Arg Phe Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 966

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 966

Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 967

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 967

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 968

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 968

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 969

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 969

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 970

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 970

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 971

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 971

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 972

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 972

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 973

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 973

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 974

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 974

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 975

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 975

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 976

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 976

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 977

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 977

Arg Ala Thr Ile Ser Ala Asp Thr Ala Lys Asn Ala Leu Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 978

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 978

Arg Ala Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 979

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 979

Arg Ala Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 980

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 980

Arg Ala Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 981

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 981

Arg Ala Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 982

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 982

Arg Ala Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 983

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 983

Arg Ala Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 984

<211> 32

<212>PRT

<213> Artificial Sequence 141A-huVH3 VH FR3

<220>

<223> humanized antibody

<400> 984

Arg Ala Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 985

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 985

Arg Ala Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 986

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 986

Arg Ala Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 987

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 987

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 988

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 988

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 989

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 989

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 990

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 990

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 991

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 991

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 992

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 992

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 993

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 993

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 994

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 994

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 995

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 995

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 996

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 996

Arg Phe Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 997

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 997

Arg Phe Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 998

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 998

Arg Phe Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 999

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 999

Arg Phe Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1000

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1000

Arg Phe Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1001

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1001

Arg Phe Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1002

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1002

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1003

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1003

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1004

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1004

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1005

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1005

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1006

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1006

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1007

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1007

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1008

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1008

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1009

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1009

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1010

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1010

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1011

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1011

Arg Ala Thr Phe Ser Arg Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1012

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1012

Arg Ala Thr Ile Ser Ala Asp Thr Ala Lys Asn Ala Leu Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1013

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1013

Arg Ala Thr Ile Ser Ala Asp Thr Ala Lys Asn Ala Leu Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1014

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1014

Arg Ala Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1015

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1015

Arg Ala Thr Ile Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1016

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1016

Arg Ala Thr Ile Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1017

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1017

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1018

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1018

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1019

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1019

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1020

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1020

Arg Phe Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1021

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1021

Arg Phe Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1022

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1022

Arg Phe Thr Ile Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1023

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1023

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1024

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1024

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Leu Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1025

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1025

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1026

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1026

Arg Ala Thr Phe Ser Ala Asp Asn Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1027

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1027

Arg Ala Thr Phe Ser Arg Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1028

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1028

Arg Ala Thr Ile Ser Ala Asp Thr Ala Lys Asn Ala Leu Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1029

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1029

Arg Phe Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1030

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3 VH FR3

<400> 1030

Arg Ala Thr Phe Ser Ala Asp Thr Ala Lys Asn Ser Ala Tyr Met Gln

1 5 10 15

Leu Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly

20 25 30

<210> 1031

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR1

<400> 1031

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys

20

<210> 1032

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR1

<400> 1032

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Leu Ser Cys

20

<210> 1033

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR1

<400> 1033

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Met Ser Cys

20

<210> 1034

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR1

<400> 1034

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Leu Ser Cys

20

<210> 1035

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR1

<400> 1035

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Met Ser Cys

20

<210> 1036

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR1

<400> 1036

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Met Ser Cys

20

<210> 1037

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR1

<400> 1037

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Met Ser Cys

20

<210> 1038

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR2

<400> 1038

Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Arg Leu Leu Ile Tyr

1 5 10 15

<210> 1039

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR2

<400> 1039

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Pro Leu Ile Tyr

1 5 10 15

<210> 1040

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR2

<400> 1040

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Trp Ile Tyr

1 5 10 15

<210> 1041

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR2

<400> 1041

Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Arg Pro Leu Ile Tyr

1 5 10 15

<210> 1042

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR2

<400> 1042

Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Arg Leu Trp Ile Tyr

1 5 10 15

<210> 1043

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR2

<400> 1043

Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Pro Trp Ile Tyr

1 5 10 15

<210> 1044

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR2

<400> 1044

Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Arg Pro Trp Ile Tyr

1 5 10 15

<210> 1045

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL CDR2

<400> 1045

Ala Thr Ser Gln Leu Ala Ser

15

<210> 1046

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL CDR2

<400> 1046

Ala Thr Ser Ser Leu Ala Ser

15

<210> 1047

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL CDR2

<400> 1047

Ala Thr Ser Asp Leu Ala Ser

15

<210> 1048

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL CDR2

<400> 1048

Ala Thr Ser Ala Leu Ala Ser

15

<210> 1049

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR3

<400> 1049

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1050

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR3

<400> 1050

Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1051

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR3

<400> 1051

Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Arg Val Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1052

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR3

<400> 1052

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1053

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR3

<400> 1053

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Arg Val Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1054

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR3

<400> 1054

Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Arg Val Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1055

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL FR3

<400> 1055

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Arg Val Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1056

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL CDR3

<400> 1056

Gln Gln Trp Ser Ser Gln Pro Tyr Thr

15

<210> 1057

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK3 VL CDR3

<400> 1057

Gln Gln Trp Ser Ser Ser Pro Tyr Thr

15

<210> 1058

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody

<400> 1058

Gln Gln Trp Ser Ser Ala Pro Tyr Thr

15

<210> 1059

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK1 VL FR1

<400> 1059

Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys

20

<210> 1060

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK1 VL FR1

<400> 1060

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Met Thr Cys

20

<210> 1061

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK1 VL FR1

<400> 1061

Asp Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Met Thr Cys

20

<210> 1062

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK1 VL FR2

<400> 1062

Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Pro Leu Ile Tyr

1 5 10 15

<210> 1063

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK1 VL FR2

<400> 1063

Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Trp Ile Tyr

1 5 10 15

<210> 1064

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK1 VL FR2

<400> 1064

Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Leu Ile Tyr

1 5 10 15

<210> 1065

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK1 VL FR2

<400> 1065

Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Lys Leu Trp Ile Tyr

1 5 10 15

<210> 1066

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK1 VL FR2

<400> 1066

Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Pro Trp Ile Tyr

1 5 10 15

<210> 1067

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK1 VL FR2

<400> 1067

Trp Tyr Gln Gln Lys Pro Gly Lys Ser Pro Lys Pro Trp Ile Tyr

1 5 10 15

<210> 1068

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK1 VL FR3

<400> 1068

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

20 25 30

<210> 1069

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVK1 VL FR3

<400> 1069

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Ser Val Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

20 25 30

<210> 1070

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3b VH CDR2

<400> 1070

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 1071

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3b VH CDR2

<400> 1071

Glu Ile Leu Pro Gly Ser Gly Ser Thr Gln Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 1072

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3b VH CDR2

<400> 1072

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asp Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 1073

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3b VH CDR2

<400> 1073

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ala Tyr Ala Asp Ser Val Lys

1 5 10 15

Gly

<210> 1074

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3b VH CDR2

<400> 1074

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Ala Asp Ser Phe Lys

1 5 10 15

Gly

<210> 1075

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3b VH CDR2

<400> 1075

Glu Ile Leu Pro Gly Ser Gly Ser Thr Gln Tyr Ala Asp Ser Phe Lys

1 5 10 15

Gly

<210> 1076

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3b VH CDR2

<400> 1076

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Ala Asp Ser Phe Lys

1 5 10 15

Gly

<210> 1077

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3b VH CDR2

<400> 1077

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asp Tyr Ala Asp Ser Phe Lys

1 5 10 15

Gly

<210> 1078

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A-huVH3b VH CDR2

<400> 1078

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ala Tyr Ala Asp Ser Phe Lys

1 5 10 15

Gly

<210> 1079

<211> 311

<212>PRT

<213> Homo sapiens

<220>

<223> C10orf54 polypeptide

<400> 1079

Met Gly Val Pro Thr Ala Leu Glu Ala Gly Ser Trp Arg Trp Gly Ser

1 5 10 15

Leu Leu Phe Ala Leu Phe Leu Ala Ala Ser Leu Gly Pro Val Ala Ala

20 25 30

Phe Lys Val Ala Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Val Thr Leu Thr Cys Arg Leu Leu Gly Pro Val Asp Lys Gly His

50 55 60

Asp Val Thr Phe Tyr Lys Thr Trp Tyr Arg Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Thr Cys Ser Glu Arg Arg Pro Ile Arg Asn Leu Thr Phe Gln Asp

85 90 95

Leu His Leu His His Gly Gly His Gln Ala Ala Asn Thr Ser His Asp

100 105 110

Leu Ala Gln Arg His Gly Leu Glu Ser Ala Ser Asp His His Gly Asn

115 120 125

Phe Ser Ile Thr Met Arg Asn Leu Thr Leu Leu Asp Ser Gly Leu Tyr

130 135 140

Cys Cys Leu Val Val Glu Ile Arg His His His Ser Glu His Arg Val

145 150 155 160

His Gly Ala Met Glu Leu Gln Val Gln Thr Gly Lys Asp Ala Pro Ser

165 170 175

Asn Cys Val Val Tyr Pro Ser Ser Ser Gln Asp Ser Glu Asn Ile Thr

180 185 190

Ala Ala Ala Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu

195 200 205

Pro Leu Ile Leu Leu Leu Val Tyr Lys Gln Arg Gln Ala Ala Ser Asn

210 215 220

Arg Arg Ala Gln Glu Leu Val Arg Met Asp Ser Asn Ile Gln Gly Ile

225 230 235 240

Glu Asn Pro Gly Phe Glu Ala Ser Pro Pro Ala Gln Gly Ile Pro Glu

245 250 255

Ala Lys Val Arg His Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser

260 265 270

Glu Ser Gly Arg His Leu Leu Ser Glu Pro Ser Thr Pro Leu Ser Pro

275 280 285

Pro Gly Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp

290 295 300

Ser Pro Asn Phe Glu Val Ile

305 310

<210> 1080

<211> 936

<212> DNA

<213> Homo sapiens

<220>

<223> cDNA nucleic acid sequence encoding the C10orf54 polypeptide

<400> 1080

atgggcgtcc ccacggccct ggaggccggc agctggcgct ggggatccct gctcttcgct 60

ctcttcctgg ctgcgtccct aggtccggtg gcagccttca aggtcgccac gccgtattcc 120

ctgtatgtct gtcccgaggg gcagaacgtc accctcacct gcaggctctt gggccctgtg 180

gacaaagggc acgatgtgac cttctacaag acgtggtacc gcagctcgag gggcgaggtg 240

cagacctgct cagagcgccg gcccatccgc aacctcacgt tccaggacct tcacctgcac 300

catggaggcc accaggctgc caacaccagc cacgacctgg ctcagcgcca cgggctggag 360

tcggcctccg accaccatgg caacttctcc atcaccatgc gcaacctgac cctgctggat 420

agcggcctct actgctgcct ggtggtggag atcaggcacc accactcgga gcacagggtc 480

catggtgcca tggagctgca ggtgcagaca ggcaaagatg caccatccaa ctgtgtggtg 540

tacccatcct cctcccagga tagtgaaaac atcacggctg cagccctggc tacgggtgcc 600

tgcatcgtag gaatcctctg cctccccctc atcctgctcc tggtctacaa gcaaaggcag 660

gcagcctcca accgccgtgc ccaggagctg gtgcggatgg acagcaacat tcaagggatt 720

gaaaaccccg gctttgaagc ctcaccacct gcccagggga tacccgaggc caaagtcagg 780

caccccctgt cctatgtggc ccagcggcag ccttctgagt ctgggcggca tctgctttcg 840

gagcccagca cccccctgtc tcctccaggc cccggagacg tcttcttccc atccctggac 900

cctgtccctg actctccaaa ctttgaggtc atctag 936

<210> 1081

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR1 determined by IMGT

<400> 1081

Gly Tyr Thr Phe Ser Thr His Trp

15

<210> 1082

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR2 determined by IMGT

<400> 1082

Ile Leu Pro Gly Ser Gly Ser Thr

15

<210> 1083

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR3 determined by IMGT

<400> 1083

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Tyr

1 5 10

<210> 1084

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VL CDR1 determined by IMGT

<400> 1084

Gln Ser Ile Val His Ser Asn Gly Asn Thr Tyr

1 5 10

<210> 1085

<211> 3

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VL CDR2 determined by IMGT

<400> 1085

Lys Leu Ser

1

<210> 1086

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR1 determined by Kabat

<400> 1086

Thr His Trp Ile Glu

15

<210> 1087

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR1 determined by chothia

<400> 1087

Gly Tyr Thr Phe Ser Thr His

15

<210> 1088

<211> 4

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR2 determined by chothia

<400> 1088

Pro Gly Ser Gly

1

<210> 1089

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR3 determined by chothia

<400> 1089

Leu Leu Tyr Tyr Tyr Ala Met Asp

15

<210> 1090

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VL CDR1 determined by chothia

<400> 1090

Ser Gln Ser Ile Val His Ser Asn Gly Asn Thr Tyr

1 5 10

<210> 1091

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VL CDR3 determined by chothia

<400> 1091

Gly Ser His Phe Pro Tyr

15

<210> 1092

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR1 determined by Contact

<400> 1092

Ser Thr His Trp Ile Glu

15

<210> 1093

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR2 determined by Contact

<400> 1093

Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser

1 5 10

<210> 1094

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR3 determined by Contact

<400> 1094

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp

1 5 10

<210> 1095

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VL CDR1 determined by Contact

<400> 1095

Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr

1 5 10

<210> 1096

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VL CDR2 determined by Contact

<400> 1096

Leu Leu Ile Tyr Lys Leu Ser Asn Arg Phe

1 5 10

<210> 1097

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VL CDR3 determined by Contact

<400> 1097

Phe Gln Gly Ser His Phe Pro Tyr

15

<210> 1098

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 175A VH CDR2 determined by AbM

<400> 1098

Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser

1 5 10

<210> 1099

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VH CDR1 determined by IMGT

<400> 1099

Gly Tyr Ser Phe Thr Gly Tyr Asn

15

<210> 1100

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VH CDR2 determined by IMGT

<400> 1100

Ile Asp Pro Tyr Tyr Asp Tyr Thr

15

<210> 1101

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VH CDR3 determined by IMGT

<400> 1101

Ala Thr Ser Thr Met Ile Thr Pro Phe Asp Tyr

1 5 10

<210> 1102

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VL CDR1 determined by IMGT

<400> 1102

Gln Ser Ile Val His Ser Asn Gly Asn Thr Tyr

1 5 10

<210> 1103

<211> 3

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VL CDR2 determined by IMGT

<400> 1103

Lys Val Ser

1

<210> 1104

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VH CDR1 determined by Kabat

<400> 1104

Gly Tyr Asn Met Asn

15

<210> 1105

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VH CDR1 determined by Chothia

<400> 1105

Gly Tyr Ser Phe Thr Gly Tyr

15

<210> 1106

<211> 4

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VH CDR2 determined by Chothia

<400> 1106

Pro Tyr Tyr Asp

1

<210> 1107

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VH CDR3 determined by Chothia

<400> 1107

Thr Met Ile Thr Pro Phe Asp

15

<210> 1108

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VL CDR1 determined by Chothia

<400> 1108

Ser Gln Ser Ile Val His Ser Asn Gly Asn Thr Tyr

1 5 10

<210> 1109

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VL CDR3 determined by Chothia

<400> 1109

Gly Ser His Val Pro Trp

15

<210> 1110

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VH CDR1 determined by Contact

<400> 1110

Thr Gly Tyr Asn Met Asn

15

<210> 1111

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VH CDR2 determined by Contact

<400> 1111

Trp Ile Gly Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser

1 5 10

<210> 1112

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VH CDR3 determined by Contact

<400> 1112

Ala Thr Ser Thr Met Ile Thr Pro Phe Asp

1 5 10

<210> 1113

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VL CDR1 determined by Contact

<400> 1113

Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr

1 5 10

<210> 1114

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VL CDR2 determined by Contact

<400> 1114

Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe

1 5 10

<210> 1115

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VL CDR3 determined by Contact

<400> 1115

Phe Gln Gly Ser His Val Pro Trp

15

<210> 1116

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 76E1 VH CDR2 determined by AbM

<400> 1116

Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser

1 5 10

<210> 1117

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VH CDR1 determined by IMGT

<400> 1117

Gly Tyr Thr Phe Ser Arg Tyr Trp

15

<210> 1118

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VH CDR2 determined by IMGT

<400> 1118

Ile Leu Pro Gly Ser Gly Ser Thr

15

<210> 1119

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VH CDR3 determined by IMGT

<400> 1119

Ala Gly Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly Tyr

1 5 10

<210> 1120

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VL CDR1 determined by IMGT

<400> 1120

Ser Ser Leu Ser Tyr

15

<210> 1121

<211> 3

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VL CDR2 determined by IMGT

<400> 1121

Ala Thr Ser

1

<210> 1122

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VH CDR1 determined by Kabat

<400> 1122

Arg Tyr Trp Ile Glu

15

<210> 1123

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VH CDR1 determined by Chothia

<400> 1123

Gly Tyr Thr Phe Ser Arg Tyr

15

<210> 1124

<211> 4

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VH CDR2 determined by Chothia

<400> 1124

Pro Gly Ser Gly

1

<210> 1125

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VH CDR3 determined by Chothia

<400> 1125

Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly

1 5 10

<210> 1126

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VL CDR1 determined by Chothia

<400> 1126

Ser Ser Ser Leu Ser Tyr

15

<210> 1127

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VL CDR3 determined by Chothia

<400> 1127

Trp Ser Ser Asn Pro Tyr

15

<210> 1128

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VH CDR1 determined by Contact

<400> 1128

Ser Arg Tyr Trp Ile Glu

15

<210> 1129

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VH CDR2 determined by Contact

<400> 1129

Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn

1 5 10

<210> 1130

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VH CDR3 determined by Contact

<400> 1130

Ala Gly Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly

1 5 10

<210> 1131

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VL CDR1 determined by Contact

<400> 1131

Ser Tyr Met His Trp Tyr

15

<210> 1132

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VL CDR2 determined by Contact

<400> 1132

Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala

1 5 10

<210> 1133

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VL CDR3 determined by Contact

<400> 1133

Gln Gln Trp Ser Ser Asn Pro Tyr

15

<210> 1134

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized antibody 141A VH CDR2 determined by Contact

<400> 1134

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn

1 5 10

<210> 1135

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> VH of humanized antibody hu76E1

<400> 1135

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr

20 25 30

Asn Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Asn Leu Lys Phe

50 55 60

Lys Asp Arg Val Thr Met Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Thr Ser Thr Met Ile Thr Pro Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 1136

<211> 121

<212>PRT

<213> Artificial Sequence

<220>

<223> VH of humanized antibody hu141A

<400> 1136

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Arg Tyr

20 25 30

Trp Ile Glu Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Gly Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1137

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> VH of humanized antibody hu175A

<400> 1137

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Thr His

20 25 30

Trp Ile Glu Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 1138

<211> 121

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus sequences of VH of humanized antibodies

between hu76E1 and hu175A

<220>

<221> VARIANT

<222> 31

<223> Xaa = Arg or Thr

<220>

<221> VARIANT

<222> 32

<223> Xaa = Tyr or His

<220>

<221> VARIANT

<222> 59

<223> Xaa = Asn or Ser

<220>

<221> VARIANT

<222> 99, 100, 101, 102, 103, 104, 105, 106, 107

<223> Xaa = Any Amino Acid

<220>

<221> VARIANT

<222> 108

<223> Xaa = Met or Phe

<220>

<221> VARIANT

<222> 109

<223> Xaa = Gly or Asp

<400> 1138

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Xaa Xaa

20 25 30

Trp Ile Glu Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Xaa Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ser

115 120

<210> 1139

<211> 106

<212>PRT

<213> Artificial Sequence

<220>

<223> VL of humanized antibody hu76E1

<400> 1139

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Ser Ser Leu Ser Tyr Met

20 25 30

His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Pro Trp Ile Tyr

35 40 45

Ala Thr Ser Asn Leu Ala Ser Gly Ile Pro Asp Arg Phe Ser Gly Ser

50 55 60

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu

65 70 75 80

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Tyr Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1140

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> VL of humanized antibody hu141A

<400> 1140

Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser

20 25 30

Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln Gly

85 90 95

Ser His Val Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1141

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> VL of humanized antibody hu175A

<400> 1141

Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser

20 25 30

Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Lys Leu Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln Gly

85 90 95

Ser His Phe Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1142

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus sequences of VL of humanized antibodies

between hu76E1 and hu175A

<220>

<221> VARIANT

<222> 56

<223> Xaa = Val or Leu

<220>

<221> VARIANT

<222> 99

<223> Xaa = Val or Phe

<220>

<221> VARIANT

<222> 101

<223> Xaa = Trp or Tyr

<400> 1142

Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser

20 25 30

Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Lys Xaa Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln Gly

85 90 95

Ser His Xaa Pro Xaa Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1143

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> pseudo-sequences of VH domains of murine antibodies 76E1

<400> 1143

Glu Val Gln Leu Leu Gln Ser Gly Pro Glu Leu Glu Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Ala Ala Ala

20 25 30

Ala Ala Ala Trp Val Lys Gln Ser Asn Gly Lys Ser Leu Glu Trp Ile

35 40 45

Gly Ala Ile Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala

50 55 60

Ala Ala Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Gln Leu Lys Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Thr Ala Ala Ala Ala Ala Ala Phe Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Thr Leu Thr Val Ser Ser

115

<210> 1144

<211> 121

<212>PRT

<213> Artificial Sequence

<220>

<223> pseudo-sequences of VH domains of murine antibodies 141A

<400> 1144

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ala Ala Ala

20 25 30

Ala Ala Ala Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile

35 40 45

Gly Ala Ile Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala

50 55 60

Ala Ala Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Gly Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ala

115 120

<210> 1145

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> pseudo-sequences of VH domains of murine antibodies 175A

<400> 1145

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ala Ala Ala

20 25 30

Ala Ala Ala Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile

35 40 45

Gly Ala Ile Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala

50 55 60

Ala Ala Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Ala Ala Ala Ala Ala Tyr Ala Met Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Ser Val Thr Val Ser Ser

115

<210> 1146

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> pseudo-sequences of VL domains of murine antibodies 76E1

<400> 1146

Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly

1 5 10 15

Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ala Ala Ala Ala

20 25 30

Ala Ala Ala Ala Ala Ala Ala Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Lys Leu Leu Ile Tyr Ala Ala Ala Ala Ala Ala Ala Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Asn Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Ala Gln Ala

85 90 95

Ala Ala Ala Pro Ala Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1147

<211> 106

<212>PRT

<213> Artificial Sequence

<220>

<223> pseudo-sequences of VL domains of murine antibodies 141A

<400> 1147

Gln Ile Val Leu Ser Gln Ser Pro Ala Ile Leu Ser Ala Ser Pro Gly

1 5 10 15

Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ala Ala Ala Ala Ala Ala

20 25 30

Ala Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr

35 40 45

Ala Ala Ala Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser

50 55 60

Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu

65 70 75 80

Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Ala Ala Ala Ala Pro Ala Thr

85 90 95

Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1148

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> pseudo-sequences of VL domains of murine antibodies 175A

<400> 1148

Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly

1 5 10 15

Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ala Ala Ala Ala

20 25 30

Ala Ala Ala Ala Ala Ala Ala Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Lys Leu Leu Ile Tyr Ala Ala Ala Ala Ala Ala Ala Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Ala Gln Ala

85 90 95

Ala Ala Ala Pro Ala Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1149

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> VH CDR1 of a humanized anti-C10orf54 antibody

<220>

<221> VARIANT

<222> 6

<223> Xaa = Arg or Thr

<220>

<221> VARIANT

<222> 7

<223> Xaa = Tyr or His

<400> 1149

Gly Tyr Thr Phe Ser Xaa Xaa Trp Ile Glu

1 5 10

<210> 1150

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> VH CDR2 of a humanized anti-C10orf54 antibody

<220>

<221> VARIANT

<222> 10

<223> Xaa = Asn or Ser

<400> 1150

Glu Ile Leu Pro Gly Ser Gly Ser Thr Xaa Tyr Asn Glu Lys Phe Lys

1 5 10 15

Gly

<210> 1151

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> VH CDR3 of a humanized anti-C10orf54 antibody

<220>

<221> VARIANT

<222> 1, 2, 3, 4, 5, 6, 7, 8, 9

<223> Xaa = Any Amino Acid

<220>

<221> VARIANT

<222> 10

<223> Xaa = Met or Phe

<220>

<221> VARIANT

<222> 11

<223> Xaa = Gly or Asp

<400> 1151

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Tyr

1 5 10

<210> 1152

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> VL CDR2 of a humanized anti-C10orf54 antibody

<220>

<221> VARIANT

<222> 2

<223> Xaa = Val or Leu

<400> 1152

Lys Xaa Ser Asn Arg Phe Ser

15

<210> 1153

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> VL CDR3 of a humanized anti-C10orf54 antibody

<220>

<221> VARIANT

<222> 6

<223> Xaa = Val or Phe

<220>

<221> VARIANT

<222> 8

<223> Xaa = Trp or Tyr

<400> 1153

Phe Gln Gly Ser His Xaa Pro Xaa Thr

15

<210> 1154

<211> 408

<212> DNA

<213> Artificial Sequence

<220>

<223> 5B heavy chain variable region with signal sequence

<400> 1154

atgggttgga gctgtatcat cttctttctg gtagcaacag ctacaggtgt gcactcccag 60

gtccagctgc agcagtctgg ggctgagctg gtgaggcctg gggtctcagt gaagatttcc 120

tgcaagggtt ctggctacac attcactgat tatggtatgc actgggtgaa gcagagtcat 180

gcaaagagtc tagagtggat tggaattatt gatacttact atggtgatgc tacctacaac 240

cagaagttca agggcaaggc cacgatgact gtagacaaat cctccagcac agcctatatg 300

gaacttgcca gactgacatc tgaggattct gccatctatt actgtgcaag aagggctggg 360

aatgctatgg actactgggg tcaaggaacc tcagtcaccg tctcctca 408

<210> 1155

<211> 136

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B heavy chain variable region with signal sequence

<400> 1155

Met Gly Trp Ser Cys Ile Ile Phe Phe Leu Val Ala Thr Ala Thr Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg

20 25 30

Pro Gly Val Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe

35 40 45

Thr Asp Tyr Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu

50 55 60

Glu Trp Ile Gly Ile Ile Asp Thr Tyr Tyr Gly Asp Ala Thr Tyr Asn

65 70 75 80

Gln Lys Phe Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Ser

85 90 95

Thr Ala Tyr Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile

100 105 110

Tyr Tyr Cys Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln

115 120 125

Gly Thr Ser Val Thr Val Ser Ser

130 135

<210> 1156

<211> 381

<212> DNA

<213> Artificial Sequence

<220>

<223> 5B light chain variable region with signal sequence

<400> 1156

atgaagtcac agacccaggt cttcgtattt ctactgctct gtgtgtctgg tgctcatggg 60

aatattgtga tgacccagac tcccaaattc ctgcttgtat cagcaggaga cagggttacc 120

ataacctgca aggccagtca gagtgtgagt aatgatgtag cttggtacca acagaagcca 180

gggcagtctc ctaaactgct gatatactat gcatccaatc gctacactgg agtccctgat 240

cgcttcactg gcagtggata tgggacggat ttcactttca ccatcagcac tgtgcaggct 300

gaagacctgg cagtttattt ctgtcagcag gattatagct ctcctcggac gttcggtgga 360

ggcaccaagc tggaaatcaa a 381

<210> 1157

<211> 127

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B light chain variable region with signal sequence

<400> 1157

Met Lys Ser Gln Thr Gln Val Phe Val Phe Leu Leu Leu Cys Val Ser

1 5 10 15

Gly Ala His Gly Asn Ile Val Met Thr Gln Thr Pro Lys Phe Leu Leu

20 25 30

Val Ser Ala Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser

35 40 45

Val Ser Asn Asp Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro

50 55 60

Lys Leu Leu Ile Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp

65 70 75 80

Arg Phe Thr Gly Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser

85 90 95

Thr Val Gln Ala Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr

100 105 110

Ser Ser Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

115 120 125

<210> 1158

<211> 408

<212> DNA

<213> Artificial Sequence

<220>

<223> 46A heavy chain variable region with signal sequence

<400> 1158

atgggttgga gctgtatcgt cttctttctg gtagcaacag ctacaggtgt gcactcccag 60

gtccagctgc agcaggccgg gggtgagctg gtgaggcctg gggtctcagt gaagatttcc 120

tgcaagggtt ctggctacac attcactgat tatggtatgc actgggtgaa gcagagtcat 180

gcaaagagtc tagagtggat tggaattatt aatacttact atggggatgc tacctacaac 240

cagaagttca agggcaaggc cacaatgact gtagacaaat cctccagcac agcctatatg 300

gaacttgcca gactgacatc tgaggattct gccatctatt actgtgcaag aagggctggg 360

actgctatgg actactgggg tcaaggaacc tcagtcaccg tctcctca 408

<210> 1159

<211> 136

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A heavy chain variable region with signal sequence

<400> 1159

Met Gly Trp Ser Cys Ile Val Phe Phe Leu Val Ala Thr Ala Thr Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ala Gly Gly Glu Leu Val Arg

20 25 30

Pro Gly Val Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe

35 40 45

Thr Asp Tyr Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu

50 55 60

Glu Trp Ile Gly Ile Ile Asn Thr Tyr Tyr Gly Asp Ala Thr Tyr Asn

65 70 75 80

Gln Lys Phe Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Ser

85 90 95

Thr Ala Tyr Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile

100 105 110

Tyr Tyr Cys Ala Arg Arg Ala Gly Thr Ala Met Asp Tyr Trp Gly Gln

115 120 125

Gly Thr Ser Val Thr Val Ser Ser

130 135

<210> 1160

<211> 381

<212> DNA

<213> Artificial Sequence

<220>

<223> 46A light chain variable region with signal sequence

<400> 1160

atgaagtcac agacccaggt cttcgtattt ctactgctct gtgtgtctgg tggtcatggg 60

agtattgtga tgacccagac tcccaaattc ctgcttgtat cagcaggaga cagggttacc 120

ataacctgca aggccagtca gagtgtgagt aatgatgtag cttggtacca acagaagcca 180

gggcagtctc ctaaactgct gatatactat gcatccaatc gctacactgg agtccctgat 240

cgcttcactg gcagtggata tgggacggat ttcactttca ccatcagcac tgtgcaggct 300

gaagacctgg cagtttattt ctgtcagcag gattatggct ctcctcggac gttcggtgga 360

ggcaccaagc tggaaatcaa a 381

<210> 1161

<211> 127

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A light chain variable region with signal sequence

<400> 1161

Met Lys Ser Gln Thr Gln Val Phe Val Phe Leu Leu Leu Cys Val Ser

1 5 10 15

Gly Gly His Gly Ser Ile Val Met Thr Gln Thr Pro Lys Phe Leu Leu

20 25 30

Val Ser Ala Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser

35 40 45

Val Ser Asn Asp Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro

50 55 60

Lys Leu Leu Ile Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp

65 70 75 80

Arg Phe Thr Gly Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser

85 90 95

Thr Val Gln Ala Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr

100 105 110

Gly Ser Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

115 120 125

<210> 1162

<211> 408

<212> DNA

<213> Artificial Sequence

<220>

<223> 97A heavy chain variable region with signal sequence

<400> 1162

atgggttgga gctgtatcat cttctttctg gtagcaacag ctacaggtgt gcactcccag 60

gtccagctgc agcagtctgg ggctgagctg gtgaggcctg gggtctcagt gaagatttcc 120

tgcaagggtt ctggctacac attcactgat tatggtatgc actgggtgaa gcagagtcat 180

gcaaagagtc tagagtggat tggagttatt gatacttact atggtgatgc tagtaacaac 240

cagaagttca agggcaaggc cacaatgact gtagacaaat cctccagcac agcctatatg 300

gaacttgcca gactgacatc tgaggattct gccatctatt actgtgcaag aagggctggg 360

aatgctatgg actactgggg tcaaggaacc tcagtcaccg tctcctca 408

<210> 1163

<211> 136

<212>PRT

<213> Artificial Sequence

<220>

<223> 97A heavy chain variable region with signal sequence

<400> 1163

Met Gly Trp Ser Cys Ile Ile Phe Phe Leu Val Ala Thr Ala Thr Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg

20 25 30

Pro Gly Val Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe

35 40 45

Thr Asp Tyr Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu

50 55 60

Glu Trp Ile Gly Val Ile Asp Thr Tyr Tyr Gly Asp Ala Ser Asn Asn

65 70 75 80

Gln Lys Phe Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Ser

85 90 95

Thr Ala Tyr Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile

100 105 110

Tyr Tyr Cys Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln

115 120 125

Gly Thr Ser Val Thr Val Ser Ser

130 135

<210> 1164

<211> 381

<212> DNA

<213> Artificial Sequence

<220>

<223> 97A light chain variable region with signal sequence

<400> 1164

atgaagtcac agacccaggt cttcgtattt ctactgctct gtgtgtctgg tgctcatggg 60

agtattgtga tgacccagac tcccaaattc ctgcttgtat cagcaggaga cagggttgcc 120

ataacctgca aggccagtca gagtgtgagt aatgatgtag cttggtacca acagaagcca 180

gggcagtctc ctaaactgct gatatactat gcatccaatc gctacactgg agtccctgat 240

cgcttcactg gcagtggata tgggacggat ttcactttca ccatcagcac tgtgcaggct 300

gaagacctgg cagtttattt ctgtcagcag gattatggct ctcctcggac gttcggtgga 360

ggcaccaagc tggaaatcaa a 381

<210> 1165

<211> 127

<212>PRT

<213> Artificial Sequence

<220>

<223> 97A light chain variable region with signal sequence

<400> 1165

Met Lys Ser Gln Thr Gln Val Phe Val Phe Leu Leu Leu Cys Val Ser

1 5 10 15

Gly Ala His Gly Ser Ile Val Met Thr Gln Thr Pro Lys Phe Leu Leu

20 25 30

Val Ser Ala Gly Asp Arg Val Ala Ile Thr Cys Lys Ala Ser Gln Ser

35 40 45

Val Ser Asn Asp Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro

50 55 60

Lys Leu Leu Ile Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp

65 70 75 80

Arg Phe Thr Gly Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser

85 90 95

Thr Val Gln Ala Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr

100 105 110

Gly Ser Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

115 120 125

<210> 1166

<211> 366

<212> DNA

<213> Artificial Sequence

<220>

<223> 128A heavy chain variable region with signal sequence

<400> 1166

atgggttgga gctgtatcat cttctttctg gtagcaacag ctacaggtgt gcactcccag 60

gtccagctgc agcagtctgg ggctgagctg gtgaggcctg gggtctcagt gaagatttcc 120

tgcaagggtt ctggctacac attcactgat tatggtatgc actgggtgaa gcagagtcat 180

gcaaagagtc tagagtggat tggacttatt gatacttact atggtgatgc tacctacaac 240

cacaaattca agggcaaggc cacgatgact gtagacaaat cctccagaac agcctatatg 300

gaacttgcca gactgacatc tgaggattct gccatctatt actgtgcaag aagggctggg 360

aatgct 366

<210> 1167

<211> 136

<212>PRT

<213> Artificial Sequence

<220>

<223> 128A heavy chain variable region with signal sequence

<400> 1167

Met Gly Trp Ser Cys Ile Ile Phe Phe Leu Val Ala Thr Ala Thr Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg

20 25 30

Pro Gly Val Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe

35 40 45

Thr Asp Tyr Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu

50 55 60

Glu Trp Ile Gly Leu Ile Asp Thr Tyr Tyr Gly Asp Ala Thr Tyr Asn

65 70 75 80

His Lys Phe Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Arg

85 90 95

Thr Ala Tyr Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile

100 105 110

Tyr Tyr Cys Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln

115 120 125

Gly Thr Ser Val Thr Ala Ser Ser

130 135

<210> 1168

<211> 381

<212> DNA

<213> Artificial Sequence

<220>

<223> 128A light chain variable region with signal sequence

<400> 1168

atgaagtcac agacccaggt cttcgtattt ctactgctct gtgtgtctgg tactcatggg 60

aatattgcga tgacccagac tcccaaattc ctgcttgtat cagcaggaga cagggttacc 120

ataacctgca aggccagtca gagtgtgagt aatgatatag cttggtacca acagaagcca 180

ggacagtctc ctagattgct gatatactat gcatccaatc gctacactgg agtccctgat 240

cgcttcactg gcagtggata tgggacggat ttcactttca ccatcagcac tgtgcaggct 300

gaagacctgg cagtttattt ctgtcagcag gattatagct ctcctcggac gttcggtgga 360

ggcaccaagc tggaaatcaa a 381

<210> 1169

<211> 127

<212>PRT

<213> Artificial Sequence

<220>

<223> 128A light chain variable region with signal sequence

<400> 1169

Met Lys Ser Gln Thr Gln Val Phe Val Phe Leu Leu Leu Cys Val Ser

1 5 10 15

Gly Thr His Gly Asn Ile Ala Met Thr Gln Thr Pro Lys Phe Leu Leu

20 25 30

Val Ser Ala Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser

35 40 45

Val Ser Asn Asp Ile Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro

50 55 60

Arg Leu Leu Ile Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp

65 70 75 80

Arg Phe Thr Gly Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser

85 90 95

Thr Val Gln Ala Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr

100 105 110

Ser Ser Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

115 120 125

<210> 1170

<211> 408

<212> DNA

<213> Artificial Sequence

<220>

<223> 146C heavy chain variable region with signal sequence

<400> 1170

atgggttgga gctgtatcat cttctttctg gtagcaacag ctacaggtgt gcactcccag 60

gtccagctgc agcagtctgg ggctgagctg gtgaggcctg gggtctcagt gaagatttcc 120

tgcaagggtt ctggctacac attcactgat tatggtatgc actgggtgaa gcagagtcat 180

gcaaagagtc tagagtggat tggacttatt gatacttact atggtgatgc tacctacaac 240

cacaaattca agggcaaggc cacgatgact gtagacaaat cctccagaac agcctatatg 300

gaacttgcca gactgacatc tgaggattct gccatctatt actgtgcaag aagggctggg 360

aatgctatgg actactgggg tcaaggaacc tcagtcaccg cctcctca 408

<210> 1171

<211> 136

<212>PRT

<213> Artificial Sequence

<220>

<223> 146C heavy chain variable region with signal sequence

<400> 1171

Met Gly Trp Ser Cys Ile Ile Phe Phe Leu Val Ala Thr Ala Thr Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg

20 25 30

Pro Gly Val Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe

35 40 45

Thr Asp Tyr Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu

50 55 60

Glu Trp Ile Gly Leu Ile Asp Thr Tyr Tyr Gly Asp Ala Thr Tyr Asn

65 70 75 80

His Lys Phe Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Arg

85 90 95

Thr Ala Tyr Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile

100 105 110

Tyr Tyr Cys Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln

115 120 125

Gly Thr Ser Val Thr Ala Ser Ser

130 135

<210> 1172

<211> 381

<212> DNA

<213> Artificial Sequence

<220>

<223> 146C light chain variable region with signal sequence

<400> 1172

atgaagtcac agacccaggt cttcgtattt ctactgctct gtgtgtctgg tactcatggg 60

aatattgcga tgacccagac tcccaaattc ctgcttgtat cagcaggaga cagggttacc 120

ataacctgca aggccagtca gagtgtgagt aatgatatag cttggtacca acagaagcca 180

ggacagtctc ctagattgct gatatactat gcatccaatc gctacactgg agtccctgat 240

cgcttcactg gcagtggata tgggacggat ttcactttca ccatcagcac tgtgcaggct 300

gaagacctgg cagtttattt ctgtcagcag gattatagct ctcctcggac gttcggtgga 360

ggcaccaagc tggaaatcaa a 381

<210> 1173

<211> 127

<212>PRT

<213> Artificial Sequence

<220>

<223> 146C light chain variable region with signal sequence

<400> 1173

Met Lys Ser Gln Thr Gln Val Phe Val Phe Leu Leu Leu Cys Val Ser

1 5 10 15

Gly Thr His Gly Asn Ile Ala Met Thr Gln Thr Pro Lys Phe Leu Leu

20 25 30

Val Ser Ala Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser

35 40 45

Val Ser Asn Asp Ile Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro

50 55 60

Arg Leu Leu Ile Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp

65 70 75 80

Arg Phe Thr Gly Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser

85 90 95

Thr Val Gln Ala Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr

100 105 110

Ser Ser Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

115 120 125

<210> 1174

<211> 408

<212> DNA

<213> Artificial Sequence

<220>

<223> 208A heavy chain variable region with signal sequence

<400> 1174

atgggttgga gctgtatcat cttctttctg gtagcaacag ctacaggtgt gcactcccag 60

gtccagctgc agcagtctgg ggctgagctg gtgaggcctg gggtctcagt gaagatttcc 120

tgcaagggtt ctggctacac attcactgat tatggtatgc actgggtgaa gcagagtcat 180

gcaaagagtc tagagtggat tggagttatt gatacttact atggtgatgc tggctacaac 240

cagaagttca agggcaaggc cacaatgact gtagacaaat cctccagcac agcctatatg 300

gaacttgcca gactgacatc tgaggattct gccatctatt actgtgcaag aagggctgga 360

aatgctatgg actactgggg tcaaggaacc tcagtcaccg tctcctca 408

<210> 1175

<211> 136

<212>PRT

<213> Artificial Sequence

<220>

<223> 208A heavy chain variable region with signal sequence

<400> 1175

Met Gly Trp Ser Cys Ile Ile Phe Phe Leu Val Ala Thr Ala Thr Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg

20 25 30

Pro Gly Val Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe

35 40 45

Thr Asp Tyr Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu

50 55 60

Glu Trp Ile Gly Val Ile Asp Thr Tyr Tyr Gly Asp Ala Gly Tyr Asn

65 70 75 80

Gln Lys Phe Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Ser

85 90 95

Thr Ala Tyr Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile

100 105 110

Tyr Tyr Cys Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln

115 120 125

Gly Thr Ser Val Thr Val Ser Ser

130 135

<210> 1176

<211> 381

<212> DNA

<213> Artificial Sequence

<220>

<223> 208A light chain variable region with signal sequence

<400> 1176

atgaagtcac agacccaggt cttcgtattt ctactgctct gtgtgtctgg tgctcttggg 60

agtattgtga tgacccagac tcccaaattc ctgcttgtat cagcaggaga cagggtcacc 120

ataacctgca aggccagtca gagtgtgagt aatgatgttg cttggtacca acagaagcca 180

gggcagtctc ctaaactgct gatatactat gcatccaatc gctacactgg agtccctgat 240

cgcttcactg gcagtggata tgggacggat ttcactttca ccatcagcac tgtgcaggct 300

gaggacctgg cagtttattt ctgtcagcag gattatagct ctcctcggac gttcggtgga 360

ggcaccaagc tggaaatcaa a 381

<210> 1177

<211> 127

<212>PRT

<213> Artificial Sequence

<220>

<223> 208A light chain variable region with signal sequence

<400> 1177

Met Lys Ser Gln Thr Gln Val Phe Val Phe Leu Leu Leu Cys Val Ser

1 5 10 15

Gly Ala Leu Gly Ser Ile Val Met Thr Gln Thr Pro Lys Phe Leu Leu

20 25 30

Val Ser Ala Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser

35 40 45

Val Ser Asn Asp Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro

50 55 60

Lys Leu Leu Ile Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp

65 70 75 80

Arg Phe Thr Gly Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser

85 90 95

Thr Val Gln Ala Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr

100 105 110

Ser Ser Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

115 120 125

<210> 1178

<211> 411

<212> DNA

<213> Artificial Sequence

<220>

<223> 215A heavy chain variable region with signal sequence

<400> 1178

atgggatgga gctggatctt tctcttcctc ctgtcaggaa ctgcaggtgt ccactctgag 60

gtccagctgc agcagtctgg acctgagttg gtgaagcctg gtgcttcaat gaagatatcc 120

tgcaaggctt ctggtttctc tttcactggc tacaccatga actgggtgaa gcagagccat 180

ggaaagaacc ttgagtggat tggacttatt agtccttaca atggtggtac tagctacaac 240

cagaagttca agggcaaggc cacattaact gtagataagt catccagcac agcctacatg 300

gagctcctca gtctgacatc tgaggactct gcagtctatt actgtgcaag aagggcctac 360

ggctatgcta tggactactg gggtcaagga acctcagtca ccgtctcctc a 411

<210> 1179

<211> 137

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A heavy chain variable region with signal sequence

<400> 1179

Met Gly Trp Ser Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly

1 5 10 15

Val His Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys

20 25 30

Pro Gly Ala Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Phe Ser Phe

35 40 45

Thr Gly Tyr Thr Met Asn Trp Val Lys Gln Ser His Gly Lys Asn Leu

50 55 60

Glu Trp Ile Gly Leu Ile Ser Pro Tyr Asn Gly Gly Thr Ser Tyr Asn

65 70 75 80

Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser

85 90 95

Thr Ala Tyr Met Glu Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Arg Ala Tyr Gly Tyr Ala Met Asp Tyr Trp Gly

115 120 125

Gln Gly Thr Ser Val Thr Val Ser Ser

130 135

<210> 1180

<211> 384

<212> DNA

<213> Artificial Sequence

<220>

<223> 215A light chain variable region with signal sequence

<400> 1180

atggattttc aagtgcagat tttcagcttc ctgctaatca gtgcctcagt catactgtcc 60

agaggacaaa ttgttctcac ccagtctcca gcaatcatgt ctgcatctcc aggggagaag 120

gtcaccatga cctgcagtgc cagctcaagt gtaagttaca tgttctggta ccagcagaag 180

ccaggatcct cccccagact cctgatttat gacacatcca acctggcttc tggagtccct 240

cttcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag ccgaatggag 300

gctgaggatg ctgccactta ttactgccag cagtggagta gttacccatt cacgttcggc 360

tcggggacaa agttggaaat aaaa 384

<210> 1181

<211> 128

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A light chain variable region with signal sequence

<400> 1181

Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser

1 5 10 15

Val Ile Leu Ser Arg Gly Gln Ile Val Leu Thr Gln Ser Pro Ala Ile

20 25 30

Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser

35 40 45

Ser Ser Val Ser Tyr Met Phe Trp Tyr Gln Gln Lys Pro Gly Ser Ser

50 55 60

Pro Arg Leu Leu Ile Tyr Asp Thr Ser Asn Leu Ala Ser Gly Val Pro

65 70 75 80

Leu Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile

85 90 95

Ser Arg Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp

100 105 110

Ser Ser Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys

115 120 125

<210> 1182

<211> 411

<212> DNA

<213> Artificial Sequence

<220>

<223> 26A heavy chain variable region with signal sequence

<400> 1182

atgggatgga gctggatctt tctcttcctc ctgtcaggaa ctgcaggtgt ccactctgag 60

gtccagctgc agcagtctgg acctgagctg gtgaagcctg gtgcttcaat gaagatatcc 120

tgcaaggctt ctggtttctc attcactggc tacaccatga actgggtgaa gcagagccat 180

gtaaagaacc ttgagtggat tggacttatt agtccttaca atggtggtac tagctacaac 240

cagaagttca agggcaaggc cacattaact gtagacaagt catccagcac agcctacatg 300

gagctcctca gtctgacatc tgaggactct gcagtctatt actgtgcaag aagggcctac 360

ggctatgcta tggactactg gggtcaagga acctcagtca ccgtctcctc a 411

<210> 1183

<211> 137

<212>PRT

<213> Artificial Sequence

<220>

<223> 26A heavy chain variable region with signal sequence

<400> 1183

Met Gly Trp Ser Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly

1 5 10 15

Val His Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys

20 25 30

Pro Gly Ala Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Phe Ser Phe

35 40 45

Thr Gly Tyr Thr Met Asn Trp Val Lys Gln Ser His Val Lys Asn Leu

50 55 60

Glu Trp Ile Gly Leu Ile Ser Pro Tyr Asn Gly Gly Thr Ser Tyr Asn

65 70 75 80

Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser

85 90 95

Thr Ala Tyr Met Glu Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Arg Ala Tyr Gly Tyr Ala Met Asp Tyr Trp Gly

115 120 125

Gln Gly Thr Ser Val Thr Val Ser Ser

130 135

<210> 1184

<211> 384

<212> DNA

<213> Artificial Sequence

<220>

<223> 26A light chain variable region with signal sequence

<400> 1184

atggattttc aagtgcagat tttcagcttc ctgctaatca gtgcctcagt catactgtcc 60

agaggacaaa ttgttctcac ccagtctcca gcaatcatgt ctgcatctcc aggggagaag 120

gtcaccatga cctgcagtgc cagctcaagt gtaagttaca tgtactggta ccagcagaag 180

ccaggatcct cccccagact cctgatttat gacacatcca acctggcttc tggagtccct 240

cttcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag ccgaatggag 300

gctgaggatg ctgccactta ttactgccag cagtggagta gttacccatt cacgttcggc 360

tcggggacaa agttggaaat aaaa 384

<210> 1185

<211> 128

<212>PRT

<213> Artificial Sequence

<220>

<223> 26A light chain variable region with signal sequence

<400> 1185

Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser

1 5 10 15

Val Ile Leu Ser Arg Gly Gln Ile Val Leu Thr Gln Ser Pro Ala Ile

20 25 30

Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser

35 40 45

Ser Ser Val Ser Tyr Met Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Ser

50 55 60

Pro Arg Leu Leu Ile Tyr Asp Thr Ser Asn Leu Ala Ser Gly Val Pro

65 70 75 80

Leu Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile

85 90 95

Ser Arg Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp

100 105 110

Ser Ser Tyr Pro Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys

115 120 125

<210> 1186

<211> 417

<212> DNA

<213> Artificial Sequence

<220>

<223> 164A heavy chain variable region with signal sequence

<400> 1186

atgggatgga cctggatctt tattttaatc ctgtcagtaa ctacaggtgt ccactctgag 60

gtccagctgc agcagtctgg acctgagttg gagaagcctg gcgcttcagt gaagatatcc 120

tgcaaggctt ctggttactc attcactggc tacaacatga actgggtgaa gcagagcaat 180

ggaaagagcc ttgagtggat tggaaatatt gatccttact atggtagtgc tagctacaac 240

cagaaattca agggcaaggc cacattgact gtagacaaat cctccaccac agcctacatg 300

cagctcaaga gcctgacatc tgaagactct gcagtctatt actgtacaag aagtaattat 360

ggttactacg ggtacttcga tgtctggggc gcagggacca cggtcaccgt ctcctca 417

<210> 1187

<211> 139

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A heavy chain variable region with signal sequence

<400> 1187

Met Gly Trp Thr Trp Ile Phe Ile Leu Ile Leu Ser Val Thr Thr Gly

1 5 10 15

Val His Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Glu Lys

20 25 30

Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe

35 40 45

Thr Gly Tyr Asn Met Asn Trp Val Lys Gln Ser Asn Gly Lys Ser Leu

50 55 60

Glu Trp Ile Gly Asn Ile Asp Pro Tyr Tyr Gly Ser Ala Ser Tyr Asn

65 70 75 80

Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr

85 90 95

Thr Ala Tyr Met Gln Leu Lys Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Thr Arg Ser Asn Tyr Gly Tyr Tyr Gly Tyr Phe Asp Val

115 120 125

Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser

130 135

<210> 1188

<211> 396

<212> DNA

<213> Artificial Sequence

<220>

<223> 164A light chain variable region with signal sequence

<400> 1188

atggaatcac agactcaggt cttcctctcc ctgctgctct gggtatctgg tacctgtggg 60

aacattatga tgacacagtc gccatcatct ctggctgtgt ctgcaggaga aaaggtcact 120

atgagctgta agtccagtca aagtgtttta tacagttcaa atcagaagaa ctacttggcc 180

tggtaccagc agaaaccagg gcagtctcct aaactgctga tctattgggc atccactagg 240

gaatctggtg tccctgatcg cttcacaggc agtggatctg ggacagattt tactcttact 300

atcagcagtg tacaagctga agacctggca gtttattact gtcatcaatt cctctcctcg 360

tacacgttcg gaggggggac caagctggaa atgaaa 396

<210> 1189

<211> 132

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A light chain variable region with signal sequence

<400> 1189

Met Glu Ser Gln Thr Gln Val Phe Leu Ser Leu Leu Leu Trp Val Ser

1 5 10 15

Gly Thr Cys Gly Asn Ile Met Met Thr Gln Ser Pro Ser Ser Leu Ala

20 25 30

Val Ser Ala Gly Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser

35 40 45

Val Leu Tyr Ser Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln

50 55 60

Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg

65 70 75 80

Glu Ser Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp

85 90 95

Phe Thr Leu Thr Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr

100 105 110

Tyr Cys His Gln Phe Leu Ser Ser Tyr Thr Phe Gly Gly Gly Thr Lys

115 120 125

Leu Glu Met Lys

130

<210> 1190

<211> 390

<212> DNA

<213> Artificial Sequence

<220>

<223> 164A light chain variable region number 2 with signal sequence

<400> 1190

atggattttc aggtgcagat tttcagcttc ctgttaatca gtgtctcagt cataatgtcc 60

agaggagaaa atgtgctgac ccagtctcca gcaatcatgg ctgcatctcc aggggagaag 120

gtcaccatga cctgcagtgc cagctcaagt gtaagttcta gtaacttgca ctggtaccag 180

cagaagtcag gcacttctac caaattctgg atttatagga catccaacct ggcttcagaa 240

gtcccagctc ccttcagtgg cagtgggtct gggacctctt actctcttac aatcagcagc 300

gtggaggccg aagatgctgc cacttattac tgccagcagt ggagtggtta cccacggacg 360

ttcggtggag gcaccaagct ggaaatcaaa 390

<210> 1191

<211> 130

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A light chain variable region number 2 with signal sequence

<400> 1191

Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Val Ser

1 5 10 15

Val Ile Met Ser Arg Gly Glu Asn Val Leu Thr Gln Ser Pro Ala Ile

20 25 30

Met Ala Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser

35 40 45

Ser Ser Val Ser Ser Ser Asn Leu His Trp Tyr Gln Gln Lys Ser Gly

50 55 60

Thr Ser Thr Lys Phe Trp Ile Tyr Arg Thr Ser Asn Leu Ala Ser Glu

65 70 75 80

Val Pro Ala Pro Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu

85 90 95

Thr Ile Ser Ser Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln

100 105 110

Gln Trp Ser Gly Tyr Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu

115 120 125

Ile Lys

130

<210> 1192

<211> 139

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A heavy chain variable region with signal sequence

<400> 1192

Met Gly Trp Thr Trp Ile Phe Ile Leu Ile Leu Ser Val Thr Thr Gly

1 5 10 15

Val His Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Glu Lys

20 25 30

Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe

35 40 45

Thr Gly Ser Asn Met Asn Trp Val Lys Gln Asn Asn Gly Lys Ser Leu

50 55 60

Glu Trp Ile Gly Asn Ile Asp Pro Tyr Tyr Gly Tyr Thr Thr Tyr Asn

65 70 75 80

Gln Lys Phe Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser

85 90 95

Thr Ala Tyr Met Gln Leu Lys Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Asp Tyr Asp Tyr Ala Leu Gly Tyr Phe Asp Val

115 120 125

Trp Gly Ala Gly Thr Thr Val Thr Val Ser Ser

130 135

<210> 1193

<211> 393

<212> DNA

<213> Artificial Sequence

<220>

<223> 230A light chain variable region with signal sequence

<400> 1193

atgaagttgc ctgttaggct gttggtgctg atgttctgga ttcctgcttc cagcagtgat 60

gttgtgatga cccaaactcc actctccctg cctgtcagtc ttggagatca agcctccatc 120

tcttgcagat ctagtcagag ccttgtacac agtaatggaa acacctattt acattggtac 180

ctgcagaagc caggccagtc tccaaagctc ctgatctaca aagtttccaa ccgattttct 240

ggggtcccag acaggttcag tggcagtgga tcagggacag atttcacact caagatcagc 300

agagtggagg ctgaggatct gggagtttat ttctgctctc aaagtacaca tgttccgtac 360

acgttcggag gggggaccaa gctggaaata aaa 393

<210> 1194

<211> 131

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A light chain variable region with signal sequence

<400> 1194

Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala

1 5 10 15

Ser Ser Ser Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val

20 25 30

Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu

35 40 45

Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro

50 55 60

Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser

65 70 75 80

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

85 90 95

Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys

100 105 110

Ser Gln Ser Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu

115 120 125

Glu Ile Lys

130

<210> 1195

<211> 411

<212> DNA

<213> Artificial Sequence

<220>

<223> 76E1 heavy chain variable region with signal sequence

<400> 1195

atgggatgga cctggatctt tattttaatc ctgtcagtaa ctacaggtgt ccactctgag 60

gtccagctgc tgcagtctgg acctgagctg gagaagcctg gcgcttcagt gaagatatcc 120

tgcaaggctt ctggttactc attcactggc tacaacatga actgggtgaa gcagagcaat 180

ggaaagagcc ttgagtggat tggaaatatt gatccttact atgattatac tagttacaac 240

ctgaagttca aggacaaggc cacattgact gtagacaaat cctccagcac agcctacatg 300

cagctcaaga gcctgacatc tgaggactct gcagtctatt actgtgcaac ctctactatg 360

attactccct ttgactactg gggccaaggc accactctca cagtctcctc a 411

<210> 1196

<211> 137

<212>PRT

<213> Artificial Sequence

<220>

<223> 76E1 heavy chain variable region with signal sequence

<400> 1196

Met Gly Trp Thr Trp Ile Phe Ile Leu Ile Leu Ser Val Thr Thr Gly

1 5 10 15

Val His Ser Glu Val Gln Leu Leu Gln Ser Gly Pro Glu Leu Glu Lys

20 25 30

Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe

35 40 45

Thr Gly Tyr Asn Met Asn Trp Val Lys Gln Ser Asn Gly Lys Ser Leu

50 55 60

Glu Trp Ile Gly Asn Ile Asp Pro Tyr Tyr Asp Tyr Thr Ser Tyr Asn

65 70 75 80

Leu Lys Phe Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser

85 90 95

Thr Ala Tyr Met Gln Leu Lys Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Thr Ser Thr Met Ile Thr Pro Phe Asp Tyr Trp Gly

115 120 125

Gln Gly Thr Thr Leu Thr Val Ser Ser

130 135

<210> 1197

<211> 393

<212> DNA

<213> Artificial Sequence

<220>

<223> 76E1 light chain variable region with signal sequence

<400> 1197

atgaagttgc ctgttaggct gttggtgctg atgttctgga ttcctgcttc cagcagtgat 60

gttttgatga cccaaactcc actctccctg cctgtcagtc ttggagatca agcctccatc 120

tcttgcagat ctagtcagag cattgtacat agtaatggaa acacctattt agaatggtac 180

ctgcagaaac caggccagtc tccaaagctc ctgatctaca aagtttccaa ccgattttct 240

ggggtcccag acaggttcag tggcagtgga tcagggacag atttcacact caagatcaac 300

agagtggagg ctgaagatct gggagtttat tactgctttc aaggttcaca tgttccgtgg 360

acgttcggtg gaggcaccaa gctggaaatc aaa 393

<210> 1198

<211> 131

<212>PRT

<213> Artificial Sequence

<220>

<223> 76E1 light chain variable region with signal sequence

<400> 1198

Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala

1 5 10 15

Ser Ser Ser Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val

20 25 30

Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile

35 40 45

Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro

50 55 60

Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser

65 70 75 80

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

85 90 95

Leu Lys Ile Asn Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys

100 105 110

Phe Gln Gly Ser His Val Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu

115 120 125

Glu Ile Lys

130

<210> 1199

<211> 408

<212> DNA

<213> Artificial Sequence

<220>

<223> 53A heavy chain variable region with signal sequence

<400> 1199

atggaatgga gttggatatt tctctttctc ctgtcaggaa ctgcaggtgt ccactctgag 60

gtccagctgc agcagtctgg acctgagctg gtaaagcctg gggcttcagt gaagatgtcc 120

tgcaaggctt ctggatacac attcactagc tattttatgc actgggtgaa gcagaagcct 180

gggcagggcc ttgagtggat tggatatatt tatccttaca atgatggtac taagtacaat 240

gagaagttca aaggcaaggc cacactgact tcagacaaat cctccagcac agcctacatg 300

gagctcagca gcctgacctc tgaggactct gcggtctatt actgtgcaag atttgattac 360

gacaccctgc gatactgggg ccaaggcacc actctcacag tctcctca 408

<210> 1200

<211> 136

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A heavy chain variable region with signal sequence

<400> 1200

Met Glu Trp Ser Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly

1 5 10 15

Val His Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys

20 25 30

Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe

35 40 45

Thr Ser Tyr Phe Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu

50 55 60

Glu Trp Ile Gly Tyr Ile Tyr Pro Tyr Asn Asp Gly Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser

85 90 95

Thr Ala Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Phe Asp Tyr Asp Thr Leu Arg Tyr Trp Gly Gln

115 120 125

Gly Thr Thr Leu Thr Val Ser Ser

130 135

<210> 1201

<211> 396

<212> DNA

<213> Artificial Sequence

<220>

<223> 53A light chain variable region with signal sequence

<400> 1201

atgaagctgc ctgttctgct agtggtgctg ctattgttca cgagtccagc ctcaagtagt 60

gatgttgttc tgacccaaac tccactctct ctgcctgtca atattggaga tcaagcctct 120

atctcttgca agtctactaa gagtcttctg aatagtgatg gattcactta tttggactgg 180

tacctgcaga agccaggcca gtctccacag ctcctaatat atttggtttc taatcgattt 240

tctggagttc cagacaggtt cagtggcagt gggtcaggaa cagatttcac actcaagatc 300

agcagagtgg aggctgagga tttgggagtt tattattgct tccagagtaa ctattttccg 360

tggacgttcg gtggaggcac caagctggaa atcaaa 396

<210> 1202

<211> 132

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A light chain variable region with signal sequence

<400> 1202

Met Lys Leu Pro Val Leu Leu Val Val Leu Leu Leu Phe Thr Ser Pro

1 5 10 15

Ala Ser Ser Ser Asp Val Val Leu Thr Gln Thr Pro Leu Ser Leu Pro

20 25 30

Val Asn Ile Gly Asp Gln Ala Ser Ile Ser Cys Lys Ser Thr Lys Ser

35 40 45

Leu Leu Asn Ser Asp Gly Phe Thr Tyr Leu Asp Trp Tyr Leu Gln Lys

50 55 60

Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Leu Val Ser Asn Arg Phe

65 70 75 80

Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

85 90 95

Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr

100 105 110

Cys Phe Gln Ser Asn Tyr Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys

115 120 125

Leu Glu Ile Lys

130

<210> 1203

<211> 408

<212> DNA

<213> Artificial Sequence

<220>

<223> 259A heavy chain variable region with signal sequence

<400> 1203

atggaatgga gttggatatt tctctttctc ctgtcaggaa ctgcaggtgt ccactctgag 60

gtccagctgc agcagtctgg acctgagctg gtaaagcctg gggcttcagt gaagatgtcc 120

tgcaaggctt ctggatacac attcactagc tattttatgc actgggtgaa gcagaagcct 180

gggcagggcc ttgagtggat tggatatatt tatccttaca atgatggtac taagtacaat 240

gagaagttca aaggcaaggc cacactgact tcagacaaat cctccagcac agcctacatg 300

gacctcagca gcctgacctc tgaagactct gcggtctatt actgtgcaag atttgattac 360

gacaccctgc gatactgggg ccaaggcacc actctcacag tctcctca 408

<210> 1204

<211> 136

<212>PRT

<213> Artificial Sequence

<220>

<223> 259A heavy chain variable region with signal sequence

<400> 1204

Met Glu Trp Ser Trp Ile Phe Leu Phe Leu Leu Ser Gly Thr Ala Gly

1 5 10 15

Val His Ser Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys

20 25 30

Pro Gly Ala Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe

35 40 45

Thr Ser Tyr Phe Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu

50 55 60

Glu Trp Ile Gly Tyr Ile Tyr Pro Tyr Asn Asp Gly Thr Lys Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser

85 90 95

Thr Ala Tyr Met Asp Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Phe Asp Tyr Asp Thr Leu Arg Tyr Trp Gly Gln

115 120 125

Gly Thr Thr Leu Thr Val Ser Ser

130 135

<210> 1205

<211> 396

<212> DNA

<213> Artificial Sequence

<220>

<223> 259A light chain variable region with signal sequence

<400> 1205

atgaagctgc ctgttctgct agtggtgctg ctattgttca cgagtccagc ctcaagtagt 60

gatgttgttc tgacccaaac tccactctct ctgcctgtca atattggaga tcaagcctct 120

atctcttgca agtctactaa gagtcttctg aatagtgatg gattcactta tttggactgg 180

tacctgcaga agccaggcca gtctccacag ctcctaatat atttgatttc taatcgattt 240

tctggagttc cagacaggtt cagtggcagt gggtcaggaa cagatttcac actcaagatc 300

agcagagtgg aggctgagga tttgggagtt tattattgct tccagagtaa ctattttccg 360

tggacgttcg gtggaggcac caagctggaa atcaaa 396

<210> 1206

<211> 132

<212>PRT

<213> Artificial Sequence

<220>

<223> 259A light chain variable region with signal sequence

<400> 1206

Met Lys Leu Pro Val Leu Leu Val Val Leu Leu Leu Phe Thr Ser Pro

1 5 10 15

Ala Ser Ser Ser Asp Val Val Leu Thr Gln Thr Pro Leu Ser Leu Pro

20 25 30

Val Asn Ile Gly Asp Gln Ala Ser Ile Ser Cys Lys Ser Thr Lys Ser

35 40 45

Leu Leu Asn Ser Asp Gly Phe Thr Tyr Leu Asp Trp Tyr Leu Gln Lys

50 55 60

Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr Leu Ile Ser Asn Arg Phe

65 70 75 80

Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe

85 90 95

Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr

100 105 110

Cys Phe Gln Ser Asn Tyr Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys

115 120 125

Leu Glu Ile Lys

130

<210> 1207

<211> 414

<212> DNA

<213> Artificial Sequence

<220>

<223> 33A heavy chain variable region with signal sequence

<400> 1207

atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60

gttcagctgc agcagtctgg agctgagctg atgaagcctg gggcctcagt gaagatatcc 120

tgcaaggcta ctggctacac attcagtagc tactggatag agtgggtaaa gcagaggcct 180

ggacatggcc ttgagtggat tggagagatt ttacctggaa gtggtagtac tagctacaat 240

gagaagttca agggcaaggc cacattcact gcagatacat cctccaacac agcctacatg 300

caactcagcg gcctgacatc tgaggactct gccgtctatt actgtgcaag atggttacta 360

tattactatg ctatggtcta ctggggtcaa ggaacctcag tcaccgtctc ctca 414

<210> 1208

<211> 138

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A heavy chain variable region with signal sequence

<400> 1208

Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys

20 25 30

Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe

35 40 45

Ser Ser Tyr Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu

50 55 60

Glu Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn

85 90 95

Thr Ala Tyr Met Gln Leu Ser Gly Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Val Tyr Trp

115 120 125

Gly Gln Gly Thr Ser Val Thr Val Ser Ser

130 135

<210> 1209

<211> 393

<212> DNA

<213> Artificial Sequence

<220>

<223> 33A light chain variable region with signal sequence

<400> 1209

atgaagttgc ctgttaggct gttggtgctg atgttctgga ttcctgcttc cagcagtgat 60

gttttgatga cccaaactcc actctccctg cctgtcagtc ttggagatca agcctccatc 120

tcttgcagat ctagtcagag cattgtacat agtaatggaa acacctattt agaatggtac 180

ctgcagaaac caggccagtc tccaaagctc ctgatctaca aagtttccaa ccgattttct 240

ggggtcccag acaggttcag tggcagtgga tcagggacag atttcacact caagatcagc 300

agagtggagg ctgaggatct gggagtttat tactgctttc aaggttcaca tgttccgtac 360

acgttcggag gggggaccaa gctggaaata aaa 393

<210> 1210

<211> 131

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A light chain variable region with signal sequence

<400> 1210

Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala

1 5 10 15

Ser Ser Ser Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val

20 25 30

Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile

35 40 45

Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro

50 55 60

Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser

65 70 75 80

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

85 90 95

Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys

100 105 110

Phe Gln Gly Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu

115 120 125

Glu Ile Lys

130

<210> 1211

<211> 414

<212> DNA

<213> Artificial Sequence

<220>

<223> 39A heavy chain variable region with signal sequence

<400> 1211

atggaatgga cctgggtctg tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60

gttcagctgc agcagtctgg agctgagctg atgaagcctg gggcctcagt gaagatatcc 120

tgcaaggcta ctggctacac attcagtagt aactggatag agtgggtaaa gcagaggcct 180

ggacatggcc ttgagtggat tggagagatt ttacctggaa gtggcagtac tagctacaat 240

gagaagttca agggcaaggc cacattcact gcagatacat cctccaacac agcctacatg 300

cagctcagca gcctgacatc tgaagactct gccgtctatt actgtgcaag atggttacta 360

tattactatg ctatggacta ctggggtcaa ggaacctcag tcaccgtctc ctca 414

<210> 1212

<211> 138

<212>PRT

<213> Artificial Sequence

<220>

<223> 39A heavy chain variable region with signal sequence

<400> 1212

Met Glu Trp Thr Trp Val Cys Leu Phe Leu Leu Ser Val Thr Ala Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys

20 25 30

Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe

35 40 45

Ser Ser Asn Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu

50 55 60

Glu Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn

85 90 95

Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Ser Val Thr Val Ser Ser

130 135

<210> 1213

<211> 393

<212> DNA

<213> Artificial Sequence

<220>

<223> 39A light chain variable region with signal sequence

<400> 1213

atgaagttgc ctgttaggct gttggtgctg atgttctgga ttcctgcttc cagcagtgat 60

gttttgatga cccaaactcc actctccctg cctgtcagtc ttggagatcc agcctccatc 120

tcttgcagat ctagtcagag cattgtacat aataatggaa acacctattt agaatggtac 180

ctgcagaaac caggccagtc tccaaagctc ctgatctaca aagtttccaa ccgattttct 240

ggggtcccag acaggttcag tggcagtgga tcagggacag atttcacact caagatcagc 300

agagtggagg ctgaggatct gggagtttat tactgctttc aaggttcaca tgttccgtac 360

acgttcggag gggggaccaa gctggaaata aaa 393

<210> 1214

<211> 131

<212>PRT

<213> Artificial Sequence

<220>

<223> 39A light chain variable region with signal sequence

<400> 1214

Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala

1 5 10 15

Ser Ser Ser Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val

20 25 30

Ser Leu Gly Asp Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile

35 40 45

Val His Asn Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro

50 55 60

Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser

65 70 75 80

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

85 90 95

Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys

100 105 110

Phe Gln Gly Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu

115 120 125

Glu Ile Lys

130

<210> 1215

<211> 414

<212> DNA

<213> Artificial Sequence

<220>

<223> 124A heavy chain variable region with signal sequence

<400> 1215

atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60

gttcagctgc agcagtctgg agctgagctg atgaagcctg gggcctcagt gaagatatcc 120

tgcaaggcta ctggctacac attcagtagc aactggatag agtgggtaaa gcagaggcct 180

ggacatggcc ttgagtggat gggagagatt ttacctggaa gtggcagtac tagctacaat 240

gagaagttca agggcaaggc cacattcact gcagatacat cctccaacac agcctacatg 300

cagctcagca gcctgacatc tgaagactct gccgtctatt actgtgcaag atggttacta 360

tattactatg ctatggactt ctggggtcaa ggaacctcag tcaccgtctc ctca 414

<210> 1216

<211> 138

<212>PRT

<213> Artificial Sequence

<220>

<223> 124A heavy chain variable region with signal sequence

<400> 1216

Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys

20 25 30

Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe

35 40 45

Ser Ser Asn Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu

50 55 60

Glu Trp Met Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn

85 90 95

Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Phe Trp

115 120 125

Gly Gln Gly Thr Ser Val Thr Val Ser Ser

130 135

<210> 1217

<211> 393

<212> DNA

<213> Artificial Sequence

<220>

<223> 124A light chain variable region with signal sequence

<400> 1217

atgaagttgc ctgttaggct gttggtgctg atgttctgga ttcctgcttc cagcagtgat 60

gttttgatga cccaaactcc actctccctg cctgtcagtc ttggagatca agcctccatc 120

tcttgcagat ctagtcagag cattgtacat aataatggaa acacctattt agaatggtac 180

ctgcagaaac caggccagtc tccaaagctc ctgatctaca aagtttccaa ccgattttct 240

ggggtcccag acaggttcag tggcagtgga tcagggacag atttcacact caagatcagc 300

agagtggagg ctgaggatct gggagtttat tactgctttc aaggttcaca tgttccgtac 360

acgttcggag gggggaccaa gctggaaata aaa 393

<210> 1218

<211> 131

<212>PRT

<213> Artificial Sequence

<220>

<223> 124A light chain variable region with signal sequence

<400> 1218

Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala

1 5 10 15

Ser Ser Ser Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val

20 25 30

Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile

35 40 45

Val His Asn Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro

50 55 60

Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser

65 70 75 80

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

85 90 95

Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys

100 105 110

Phe Gln Gly Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu

115 120 125

Glu Ile Lys

130

<210> 1219

<211> 414

<212> DNA

<213> Artificial Sequence

<220>

<223> 175A heavy chain variable region with signal sequence

<400> 1219

atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60

gttcagctgc agcagtctgg agctgagctg atgaagcctg gggcctcagt gaagatatcc 120

tgcaaggcta ctggctacac attcagtacc cactggatag agtgggtaaa gcagaggcct 180

ggacatggcc ttgagtggat tggagagatt ttacctggaa gtggtagtac tagctacaat 240

gagaagttca agggcaaggc cacattcact gcagatacat cctccaacac agcctacatg 300

caactcagca gcctgacatc tgaggactct gccgtctatt actgtgcaag atggttacta 360

tattactatg ctatggacta ctggggtcaa ggaacctcag tcaccgtctc ctca 414

<210> 1220

<211> 138

<212>PRT

<213> Artificial Sequence

<220>

<223> 175A heavy chain variable region with signal sequence

<400> 1220

Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys

20 25 30

Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe

35 40 45

Ser Thr His Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu

50 55 60

Glu Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn

85 90 95

Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Ser Val Thr Val Ser Ser

130 135

<210> 1221

<211> 393

<212> DNA

<213> Artificial Sequence

<220>

<223> 175A light chain variable region with signal sequence

<400> 1221

atgaagttgc ctgttaggct gttggtgctg atgttctgga ttcctgcttc cagcagtgat 60

gttttgatga cccaaactcc actctccctg cctgtcagtc ttggagatca agcctccatc 120

tcttgcagat ctagtcagag cattgtacat agtaatggaa acacctattt agaatggtac 180

ctgcagaaac caggccagtc tccaaagctc ctgatctaca aactttccaa ccgattttct 240

ggggtcccag acaggttcag tggcagtgga tcagggacag atttcacact caagatcagc 300

agagtggagg ctgaggatct gggagtttat tactgctttc aaggttcaca ttttccgtac 360

acgttcggag gggggaccaa gctggaaata aaa 393

<210> 1222

<211> 131

<212>PRT

<213> Artificial Sequence

<220>

<223> 175A light chain variable region with signal sequence

<400> 1222

Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala

1 5 10 15

Ser Ser Ser Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val

20 25 30

Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile

35 40 45

Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro

50 55 60

Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Leu Ser Asn Arg Phe Ser

65 70 75 80

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

85 90 95

Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys

100 105 110

Phe Gln Gly Ser His Phe Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu

115 120 125

Glu Ile Lys

130

<210> 1223

<211> 414

<212> DNA

<213> Artificial Sequence

<220>

<223> 321D heavy chain variable region with signal sequence

<400> 1223

atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60

gttcagctgc agcagtctgg agctgagctg atgaagcctg gggccgcagt gaagatatcc 120

tgcaaggcta ctggctacac attcagtagc cactggatag agtgggtaaa gcagaggcct 180

ggacatggcc ttgagtggat tggagagatt ttacctggaa gtggtagtac tgactacaat 240

gagaagttca agggcaaggc cacattcact gcagatacat cctccaacac agcctacatg 300

caactcagca gcctgacatc tgaggactct gccgtctatt actgtgcaag atggttacta 360

tattactatg ctatggacta ctggggtcaa ggaacctcag tcaccgtctc ctca 414

<210> 1224

<211> 138

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D heavy chain variable region with signal sequence

<400> 1224

Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys

20 25 30

Pro Gly Ala Ala Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe

35 40 45

Ser Ser His Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu

50 55 60

Glu Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Asp Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn

85 90 95

Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Tyr Trp

115 120 125

Gly Gln Gly Thr Ser Val Thr Val Ser Ser

130 135

<210> 1225

<211> 393

<212> DNA

<213> Artificial Sequence

<220>

<223> 321D light chain variable region with signal sequence

<400> 1225

atgaagttgc ctgttaggct gttggtgctg atgttctgga ttcctgcttc cagcagtgat 60

gttttgatga cccaaactcc actctccctg cctgtcagtc ttggagatca agcctccatc 120

tcttgcagat ctagtcagag cattgtacat agtaatggaa acacctattt agaatggtac 180

ctgcagaaac caggccagtc tccaaagctc ctgatctaca aagtttccaa ccgattttct 240

ggggtcccag acaggttcag tggcagtgga tcagggacag atttcacact caagatcacc 300

agagtggagg ctgaggatct gggagtttat tactgctttc aaggttcaca tgttccgttc 360

acgttcggag gggggaccaa gctggaaata aaa 393

<210> 1226

<211> 131

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D light chain variable region with signal sequence

<400> 1226

Met Lys Leu Pro Val Arg Leu Leu Val Leu Met Phe Trp Ile Pro Ala

1 5 10 15

Ser Ser Ser Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val

20 25 30

Ser Leu Gly Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile

35 40 45

Val His Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro

50 55 60

Gly Gln Ser Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser

65 70 75 80

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

85 90 95

Leu Lys Ile Thr Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys

100 105 110

Phe Gln Gly Ser His Val Pro Phe Thr Phe Gly Gly Gly Thr Lys Leu

115 120 125

Glu Ile Lys

130

<210> 1227

<211> 420

<212> DNA

<213> Artificial Sequence

<220>

<223> 141A heavy chain variable region with signal sequence

<400> 1227

atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60

gttcagctgc agcagtctgg agctgagctg atgaagcctg gggcctcagt gaagatatcc 120

tgcaaggcta ctggctacac attcagtagg tactggatag agtgggtaaa gcagaggcct 180

ggacatggcc ttgagtggat tggagagatt ttacctggaa gtggtagtac taactacaat 240

gagaagttca agggcaaggc cacattcact gcagatacat cctccaacac agcctacatg 300

caactcagca gcctgacatc tgaggactct gccgtctatt actgtgcagg agaggaagtc 360

tatgatggtt acccctggtt tggttactgg ggccaaggga ctctggtcac tgtctctgca 420

<210> 1228

<211> 140

<212>PRT

<213> Artificial Sequence

<220>

<223> 141A heavy chain variable region with signal sequence

<400> 1228

Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys

20 25 30

Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe

35 40 45

Ser Arg Tyr Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu

50 55 60

Glu Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn

85 90 95

Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Gly Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly

115 120 125

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala

130 135 140

<210> 1229

<211> 384

<212> DNA

<213> Artificial Sequence

<220>

<223> 141A light chain variable region with signal sequence

<400> 1229

atggattttc aagtgcagat tttcagcttc ctgctaatca gtgcttcagt cataatgtcc 60

agaggacaaa ttgttctctc ccagtctcca gcaatcctgt ctgcatctcc aggggagaag 120

gtcacaatga cttgcagggc cagctcaagt ttaagttaca tgcactggta ccagcagaag 180

ccaggatcct cccccaaacc ctggatttat gccacatcca acctggcttc tggagtccct 240

gctcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag cagagtggag 300

gctgaagatg ctgccactta ttactgccag cagtggagta gtaacccgta cacgttcgga 360

ggggggacca agctggaaat aaaa 384

<210> 1230

<211> 128

<212>PRT

<213> Artificial Sequence

<220>

<223> 141A light chain variable region with signal sequence

<400> 1230

Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser

1 5 10 15

Val Ile Met Ser Arg Gly Gln Ile Val Leu Ser Gln Ser Pro Ala Ile

20 25 30

Leu Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser

35 40 45

Ser Ser Leu Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Ser Ser

50 55 60

Pro Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile

85 90 95

Ser Arg Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp

100 105 110

Ser Ser Asn Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

115 120 125

<210> 1231

<211> 420

<212> DNA

<213> Artificial Sequence

<220>

<223> 51A heavy chain variable region with signal sequence

<400> 1231

atggaatgga cctgggtctt tctcttcctc ctgtcagtaa ctgcaggtgt ccactcccag 60

gttcagctgc agcagtctgg agctgagctg atgaagcctg gggcctcagt gaagatatcc 120

tgcaaggcta ctggctacac attcagtagg tactggatag agtgggtaaa gcagaggcct 180

ggacatggcc ttgagtggat tggagagatt ttacctggaa gtggtagtac taactacaat 240

gagaagttca agggcaaggc cacattcact gcagatacat cctccaacac agcctacatg 300

caactcagca gcctgacatc tgaggactct gccgtctatt actgtgcaag cgaggaagtc 360

tatgatggtt acccctggtt tggttactgg ggccaaggga ctctggtcac tgtctctgca 420

<210> 1232

<211> 140

<212>PRT

<213> Artificial Sequence

<220>

<223> 51A heavy chain variable region with signal sequence

<400> 1232

Met Glu Trp Thr Trp Val Phe Leu Phe Leu Leu Ser Val Thr Ala Gly

1 5 10 15

Val His Ser Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys

20 25 30

Pro Gly Ala Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe

35 40 45

Ser Arg Tyr Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu

50 55 60

Glu Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Asn

65 70 75 80

Glu Lys Phe Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn

85 90 95

Thr Ala Tyr Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val

100 105 110

Tyr Tyr Cys Ala Ser Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly

115 120 125

Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala

130 135 140

<210> 1233

<211> 384

<212> DNA

<213> Artificial Sequence

<220>

<223> 51A light chain variable region with signal sequence

<400> 1233

atggattttc aagtgcagat tttcagcttc ctgctaatca gtgcttcagt cataatgtcc 60

agaggacaaa ttgttctctc ccagtctcca gcaatcctgt ctgcatctcc aggggagaag 120

gtcacaatga cttgcagggc cagctcaagt ttaagttaca tgcactggta ccagcagagg 180

ccaggatcct cccccaaacc ctggatttat gccacatcca acctggcttc tggagtccct 240

gctcgcttca gtggcagtgg gtctgggacc tcttactctc tcacaatcag cagagtggag 300

gctgaagatg ctgccactta ttactgccag cagtggagta gtaacccgta cacgttcgga 360

ggggggacca agctggaaat aaaa 384

<210> 1234

<211> 128

<212>PRT

<213> Artificial Sequence

<220>

<223> 51A light chain variable region with signal sequence

<400> 1234

Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser

1 5 10 15

Val Ile Met Ser Arg Gly Gln Ile Val Leu Ser Gln Ser Pro Ala Ile

20 25 30

Leu Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Arg Ala Ser

35 40 45

Ser Ser Leu Ser Tyr Met His Trp Tyr Gln Gln Arg Pro Gly Ser Ser

50 55 60

Pro Lys Pro Trp Ile Tyr Ala Thr Ser Asn Leu Ala Ser Gly Val Pro

65 70 75 80

Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile

85 90 95

Ser Arg Val Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp

100 105 110

Ser Ser Asn Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

115 120 125

<210> 1235

<211> 423

<212> DNA

<213> Artificial Sequence

<220>

<223> 353A heavy chain variable region with signal sequence

<400> 1235

atggattttg ggctgatttt ttttattgtt gctcttttaa aaggggtcca gtgtgaggtg 60

aagcttctcg agtctggagg tggcctggtg cagcctggag gatccctgaa actctcctgt 120

gcagcctcag gattcgattt tagtagatac tggatgaatt gggtccggca ggctccagg 180

aaagggctag aatggattgg agaaattaat ccagatagca gtacgataaa ctatacgcca 240

tctctaaagg ataaattcat catctccaga gacaacgcca aaaatacgct gtacctgcaa 300

atgagcaaag tgagatatga ggacacagcc ctttattact gtgcaagacc gggggaaatt 360

tattactacg gtagttactg gtttgcttac tggggccaag ggactctggt cactgtctct 420

gca 423

<210> 1236

<211> 141

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A heavy chain variable region with signal sequence

<400> 1236

Met Asp Phe Gly Leu Ile Phe Phe Ile Val Ala Leu Leu Lys Gly Val

1 5 10 15

Gln Cys Glu Val Lys Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro

20 25 30

Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser

35 40 45

Arg Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu

50 55 60

Trp Ile Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Thr Pro

65 70 75 80

Ser Leu Lys Asp Lys Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Thr

85 90 95

Leu Tyr Leu Gln Met Ser Lys Val Arg Tyr Glu Asp Thr Ala Leu Tyr

100 105 110

Tyr Cys Ala Arg Pro Gly Glu Ile Tyr Tyr Tyr Gly Ser Tyr Trp Phe

115 120 125

Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala

130 135 140

<210> 1237

<211> 393

<212> DNA

<213> Artificial Sequence

<220>

<223> 353A light chain variable region with signal sequence

<400> 1237

atggagtcag acacactcct gctatgggtg ctgctgctct gggttccagg ctccactggt 60

gacattgtgc tcacccaatc tccagcttct ttggctgtgt ctctagggca gagagccacc 120

atctcctgca gagccagtga aagtgttgaa tattatggca caagtttaat gcagtggttc 180

caacagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa cgtagaatct 240

agggtccctg ccaggtttag tggcagtggg tctgggacag acttcagcct caacatccat 300

cctgtggagg aggatgatat tgcaatgtat ttctgtcagc aaagtaggaa ggatccttgg 360

acattcggtg gaggcaccaa gctggaaatc aaa 393

<210> 1238

<211> 131

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A light chain variable region with signal sequence

<400> 1238

Met Glu Ser Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro

1 5 10 15

Gly Ser Thr Gly Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala

20 25 30

Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Arg Ala Ser Glu Ser

35 40 45

Val Glu Tyr Tyr Gly Thr Ser Leu Met Gln Trp Phe Gln Gln Lys Pro

50 55 60

Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Val Glu Ser

65 70 75 80

Arg Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ser

85 90 95

Leu Asn Ile His Pro Val Glu Glu Asp Asp Ile Ala Met Tyr Phe Cys

100 105 110

Gln Gln Ser Arg Lys Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu

115 120 125

Glu Ile Lys

130

<210> 1239

<211> 408

<212> DNA

<213> Artificial Sequence

<220>

<223> 305A heavy chain variable region with signal sequence

<400> 1239

atgaaagtgt tgagtctgtt gtacctgttg acagccattc ctggtatcct gtctgatgta 60

cagcttcagg agtcaggacc tggcctcgtg aaaccttctc agtctctgtc tctcacctgc 120

tctgtcactg gctactccat caccagtggt tattactgga actggatccg gcagtttcca 180

ggaaacaaac tggaatggat gggctacata agctacgacg gtagcaataa ctacaaccca 240

tctctcaaaa atcgaatctc catcactcgt gacacatcta agaaccagtt tttcctgaag 300

ttgaattctg tgactactga ggacacagct acatattact gtgcaagacg gcatgattac 360

ctctcctttg cttactgggg ccaagggact ctggtcattg tctctgca 408

<210> 1240

<211> 136

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A heavy chain variable region with signal sequence

<400> 1240

Met Lys Val Leu Ser Leu Leu Tyr Leu Leu Thr Ala Ile Pro Gly Ile

1 5 10 15

Leu Ser Asp Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro

20 25 30

Ser Gln Ser Leu Ser Leu Thr Cys Ser Val Thr Gly Tyr Ser Ile Thr

35 40 45

Ser Gly Tyr Tyr Trp Asn Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu

50 55 60

Glu Trp Met Gly Tyr Ile Ser Tyr Asp Gly Ser Asn Asn Tyr Asn Pro

65 70 75 80

Ser Leu Lys Asn Arg Ile Ser Ile Thr Arg Asp Thr Ser Lys Asn Gln

85 90 95

Phe Phe Leu Lys Leu Asn Ser Val Thr Thr Glu Asp Thr Ala Thr Tyr

100 105 110

Tyr Cys Ala Arg Arg His Asp Tyr Leu Ser Phe Ala Tyr Trp Gly Gln

115 120 125

Gly Thr Leu Val Ile Val Ser Ala

130 135

<210> 1241

<211> 393

<212> DNA

<213> Artificial Sequence

<220>

<223> 305A light chain variable region with signal sequence

<400> 1241

atggagacag acacaatcct gctatgggtg ctgctgctct gggttccagg ctccactggt 60

gacattgtgc tgacccaatc tccagcttct ttggctgtgt ctctagggca gagggccacc 120

atctcctgca aggccagcca aagtgttgat tatgatggtg atagttatat gaactggtac 180

caacagaaac caggacagcc acccaaactc ctcatctatg ctgcatccaa tctagaatct 240

gggatcccag ccaggtttag tggcagtggg tctgggacag acttcaccct caacatccat 300

cctgtggagg aggaggatgc tgcaacctat tactgtcagc aaagtgatga ggatccgtac 360

acgttcggag gggggaccaa gctggaaata aaa 393

<210> 1242

<211> 131

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A light chain variable region with signal sequence

<400> 1242

Met Glu Thr Asp Thr Ile Leu Leu Trp Val Leu Leu Leu Trp Val Pro

1 5 10 15

Gly Ser Thr Gly Asp Ile Val Leu Thr Gln Ser Pro Ala Ser Leu Ala

20 25 30

Val Ser Leu Gly Gln Arg Ala Thr Ile Ser Cys Lys Ala Ser Gln Ser

35 40 45

Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro

50 55 60

Gly Gln Pro Pro Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser

65 70 75 80

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

85 90 95

Leu Asn Ile His Pro Val Glu Glu Glu Asp Ala Ala Thr Tyr Tyr Cys

100 105 110

Gln Gln Ser Asp Glu Asp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu

115 120 125

Glu Ile Lys

130

<210> 1243

<211> 309

<212>PRT

<213> Artificial Sequence

<220>

<223> mouse C10orf54 protein encoded by the CC2 expression

construct

<400> 1243

Met Gly Val Pro Ala Val Pro Glu Ala Ser Ser Pro Arg Trp Gly Thr

1 5 10 15

Leu Leu Leu Ala Ile Phe Leu Ala Ala Ser Arg Gly Leu Val Ala Ala

20 25 30

Phe Lys Val Thr Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Ala Thr Leu Thr Cys Arg Ile Leu Gly Pro Val Ser Lys Gly His

50 55 60

Asp Val Thr Ile Tyr Lys Thr Trp Tyr Leu Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Met Cys Lys Glu His Arg Pro Ile Arg Asn Phe Thr Leu Gln His

85 90 95

Leu Gln His His Gly Ser His Leu Lys Ala Asn Ala Ser His Asp Gln

100 105 110

Pro Gln Lys His Gly Leu Glu Leu Ala Ser Asp His His Gly Asn Phe

115 120 125

Ser Ile Thr Leu Arg Asn Val Thr Pro Arg Asp Ser Gly Leu Tyr Cys

130 135 140

Cys Leu Val Ile Glu Leu Lys Asn His His Pro Glu Gln Arg Phe Tyr

145 150 155 160

Gly Ser Met Glu Leu Gln Val Gln Ala Gly Lys Gly Ser Gly Ser Thr

165 170 175

Cys Met Ala Ser Asn Glu Gln Asp Ser Asp Ser Ile Thr Ala Ala Ala

180 185 190

Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu Pro Leu Ile

195 200 205

Leu Leu Leu Val Tyr Lys Gln Arg Gln Val Ala Ser His Arg Arg Ala

210 215 220

Gln Glu Leu Val Arg Met Asp Ser Ser Asn Thr Gln Gly Ile Glu Asn

225 230 235 240

Pro Gly Phe Glu Thr Thr Pro Pro Phe Gln Gly Met Pro Glu Ala Lys

245 250 255

Thr Arg Pro Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser Glu Ser

260 265 270

Gly Arg Tyr Leu Leu Ser Asp Pro Ser Thr Pro Leu Ser Pro Pro Gly

275 280 285

Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp Ser Pro

290 295 300

Asn Ser Glu Ala Ile

305

<210> 1244

<211> 309

<212>PRT

<213> Artificial Sequence

<220>

<223> rat C10orf54 protein encoded by the CC3 expression

construct

<400> 1244

Met Gly Val Pro Thr Val Pro Glu Ala Ser Ser Leu Arg Trp Gly Thr

1 5 10 15

Leu Leu Leu Thr Ile Phe Leu Ala Ala Ser Arg Gly Leu Val Ala Ala

20 25 30

Ile Lys Val Thr Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Val Thr Leu Thr Cys Arg Ile Leu Asp Ser Val Ser Lys Gly His

50 55 60

Asp Ala Asn Phe Leu Lys Thr Trp Phe Leu Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Val Cys Lys Glu His Arg Pro Ile Arg Asn Phe Ile Ser His His

85 90 95

Gln His His Arg Ser His Pro Ala Val Asn Ala Ser His Asp Gln Pro

100 105 110

Gln Lys His Gly Leu Glu Ile Ala Tyr Asp Asn His Gly Asn Phe Ser

115 120 125

Ile Thr Leu His Asn Val Thr Leu Ser Asp Ser Gly Leu Tyr Cys Cys

130 135 140

Leu Val Ile Glu Val Lys His His His Pro Glu Arg Arg Leu Tyr Gly

145 150 155 160

Tyr Met Glu Leu Gln Val Gln Thr Gly Lys Gly Ser Ala Ser Thr Cys

165 170 175

Thr Ala Tyr Pro Pro Asn Glu Gln Asp Ser Asp Ser Ile Thr Ala Ala

180 185 190

Ala Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu Pro Leu

195 200 205

Ile Leu Leu Leu Val Tyr Lys Gln Arg Gln Ala Ala Ser His Arg Arg

210 215 220

Ala Gln Glu Leu Val Arg Met Asp Ser Asn Thr Gln Gly Ile Glu Asn

225 230 235 240

Pro Gly Tyr Glu Thr Thr Pro Pro Phe Gln Gly Met Pro Glu Ala Lys

245 250 255

Thr Arg Pro Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser Glu Ser

260 265 270

Gly Arg His Leu Leu Ser Asp Pro Ser Thr Pro Leu Ser Pro Pro Gly

275 280 285

Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp Ser Pro

290 295 300

Asn Ser Glu Ala Ile

305

<210> 1245

<211> 311

<212>PRT

<213> Artificial Sequence

<220>

<223> cynomolgus C10orf54 protein encoded by the CC4

expression construct

<400> 1245

Met Gly Val Pro Thr Ala Pro Glu Ala Gly Cys Trp Arg Trp Gly Ser

1 5 10 15

Leu Leu Phe Ala Leu Phe Leu Ala Ala Ser Leu Gly Pro Val Ala Ala

20 25 30

Phe Lys Val Ala Thr Leu Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Val Thr Leu Thr Cys Arg Val Phe Gly Pro Val Asp Lys Gly His

50 55 60

Asp Val Thr Phe Tyr Lys Thr Trp Tyr Arg Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Thr Cys Ser Glu Arg Arg Pro Ile Arg Asn Leu Thr Phe Gln Asp

85 90 95

Leu His Leu His His Gly Gly His Gln Ala Ala Asn Thr Ser His Asp

100 105 110

Leu Ala Gln Arg His Gly Leu Glu Ser Ala Ser Asp His His Gly Asn

115 120 125

Phe Ser Ile Thr Met Arg Asn Leu Thr Leu Leu Asp Ser Gly Leu Tyr

130 135 140

Cys Cys Leu Val Val Glu Ile Arg His His His Ser Glu His Arg Val

145 150 155 160

His Gly Ala Met Glu Leu Gln Val Gln Thr Gly Lys Asp Ala Pro Ser

165 170 175

Ser Cys Val Ala Tyr Pro Ser Ser Ser Gln Glu Ser Glu Asn Ile Thr

180 185 190

Ala Ala Ala Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu

195 200 205

Pro Leu Ile Leu Leu Leu Val Tyr Lys Gln Arg Gln Ala Ala Ser Asn

210 215 220

Arg Arg Ala Gln Glu Leu Val Arg Met Asp Ser Asn Thr Gln Gly Ile

225 230 235 240

Glu Asn Pro Gly Phe Glu Ala Ser Ser Pro Ala Gln Gly Ile Leu Glu

245 250 255

Ala Lys Val Arg His Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser

260 265 270

Glu Ser Gly Arg His Leu Leu Ser Glu Pro Gly Thr Pro Leu Ser Pro

275 280 285

Pro Gly Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp

290 295 300

Ser Pro Asn Phe Glu Val Ile

305 310

<210> 1246

<211> 310

<212>PRT

<213> Artificial Sequence

<220>

<223> chimeric protein encoded by the CC5 expression construct

<400> 1246

Met Gly Val Pro Thr Ala Leu Glu Ala Gly Ser Trp Arg Trp Gly Ser

1 5 10 15

Leu Leu Phe Ala Leu Phe Leu Ala Ala Ser Leu Gly Pro Val Ala Ala

20 25 30

Phe Lys Val Ala Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Val Thr Leu Thr Cys Arg Leu Leu Gly Pro Val Asp Lys Gly His

50 55 60

Asp Val Thr Phe Tyr Lys Thr Trp Tyr Arg Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Thr Cys Ser Glu Arg Arg Pro Ile Arg Asn Leu Thr Phe Gln Asp

85 90 95

Leu His Leu His His Gly Gly His Gln Ala Ala Asn Thr Ser His Asp

100 105 110

Leu Ala Gln Arg His Gly Leu Glu Ser Ala Ser Asp His His Gly Asn

115 120 125

Phe Ser Ile Thr Met Arg Asn Leu Thr Leu Leu Asp Ser Gly Leu Tyr

130 135 140

Cys Cys Leu Val Val Glu Ile Arg His His His Ser Glu His Arg Val

145 150 155 160

His Gly Ala Met Glu Leu Gln Val Gln Ala Gly Lys Gly Ser Gly Ser

165 170 175

Thr Cys Met Ala Ser Asn Glu Gln Asp Ser Asp Ser Ile Thr Ala Ala

180 185 190

Ala Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu Pro Leu

195 200 205

Ile Leu Leu Leu Val Tyr Lys Gln Arg Gln Val Ala Ser His Arg Arg

210 215 220

Ala Gln Glu Leu Val Arg Met Asp Ser Ser Asn Thr Gln Gly Ile Glu

225 230 235 240

Asn Pro Gly Phe Glu Thr Thr Pro Pro Phe Gln Gly Met Pro Glu Ala

245 250 255

Lys Thr Arg Pro Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser Glu

260 265 270

Ser Gly Arg Tyr Leu Leu Ser Asp Pro Ser Thr Pro Leu Ser Pro Pro

275 280 285

Gly Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp Ser

290 295 300

Pro Asn Ser Glu Ala Ile

305 310

<210> 1247

<211> 310

<212>PRT

<213> Artificial Sequence

<220>

<223> chimeric protein encoded by the CC6 expression construct

<400> 1247

Met Gly Val Pro Ala Val Pro Glu Ala Ser Ser Pro Arg Trp Gly Thr

1 5 10 15

Leu Leu Leu Ala Ile Phe Leu Ala Ala Ser Arg Gly Leu Val Ala Ala

20 25 30

Phe Lys Val Thr Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Ala Thr Leu Thr Cys Arg Ile Leu Gly Pro Val Ser Lys Gly His

50 55 60

Asp Val Thr Ile Tyr Lys Thr Trp Tyr Leu Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Met Cys Lys Glu His Arg Pro Ile Arg Asn Phe Thr Leu Gln His

85 90 95

Leu Gln His His Gly Ser His Leu Lys Ala Asn Ala Ser His Asp Gln

100 105 110

Pro Gln Lys His Gly Leu Glu Leu Ala Ser Asp His His Gly Asn Phe

115 120 125

Ser Ile Thr Leu Arg Asn Val Thr Pro Arg Asp Ser Gly Leu Tyr Cys

130 135 140

Cys Leu Val Ile Glu Leu Lys Asn His His Pro Glu Gln Arg Phe Tyr

145 150 155 160

Gly Ser Met Glu Leu Gln Val Gln Thr Gly Lys Asp Ala Pro Ser Asn

165 170 175

Cys Val Val Tyr Pro Ser Ser Ser Gln Asp Ser Glu Asn Ile Thr Ala

180 185 190

Ala Ala Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu Pro

195 200 205

Leu Ile Leu Leu Leu Val Tyr Lys Gln Arg Gln Ala Ala Ser Asn Arg

210 215 220

Arg Ala Gln Glu Leu Val Arg Met Asp Ser Asn Ile Gln Gly Ile Glu

225 230 235 240

Asn Pro Gly Phe Glu Ala Ser Pro Pro Ala Gln Gly Ile Pro Glu Ala

245 250 255

Lys Val Arg His Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser Glu

260 265 270

Ser Gly Arg His Leu Leu Ser Glu Pro Ser Thr Pro Leu Ser Pro Pro

275 280 285

Gly Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp Ser

290 295 300

Pro Asn Phe Glu Val Ile

305 310

<210> 1248

<211> 309

<212>PRT

<213> Artificial Sequence

<220>

<223> chimeric protein encoded by the CC7 expression construct

<400> 1248

Met Gly Val Pro Thr Ala Leu Glu Ala Gly Ser Trp Arg Trp Gly Ser

1 5 10 15

Leu Leu Phe Ala Leu Phe Leu Ala Ala Ser Leu Gly Pro Val Ala Ala

20 25 30

Phe Lys Val Ala Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Val Thr Leu Thr Cys Arg Leu Leu Gly Pro Val Asp Lys Gly His

50 55 60

Asp Val Thr Phe Tyr Lys Thr Trp Tyr Arg Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Thr Cys Lys Glu His Arg Pro Ile Arg Asn Phe Thr Leu Gln His

85 90 95

Leu Gln His His Gly Ser His Leu Lys Ala Asn Ala Ser His Asp Gln

100 105 110

Pro Gln Lys His Gly Leu Glu Leu Ala Ser Asp His His Gly Asn Phe

115 120 125

Ser Ile Thr Leu Arg Asn Val Thr Pro Arg Asp Ser Gly Leu Tyr Cys

130 135 140

Cys Leu Val Ile Glu Leu Lys Asn His His Pro Glu Gln Arg Phe Tyr

145 150 155 160

Gly Ser Met Glu Leu Gln Val Gln Ala Gly Lys Gly Ser Gly Ser Thr

165 170 175

Cys Met Ala Ser Asn Glu Gln Asp Ser Asp Ser Ile Thr Ala Ala Ala

180 185 190

Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu Pro Leu Ile

195 200 205

Leu Leu Leu Val Tyr Lys Gln Arg Gln Val Ala Ser His Arg Arg Ala

210 215 220

Gln Glu Leu Val Arg Met Asp Ser Ser Asn Thr Gln Gly Ile Glu Asn

225 230 235 240

Pro Gly Phe Glu Thr Thr Pro Pro Phe Gln Gly Met Pro Glu Ala Lys

245 250 255

Thr Arg Pro Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser Glu Ser

260 265 270

Gly Arg Tyr Leu Leu Ser Asp Pro Ser Thr Pro Leu Ser Pro Pro Gly

275 280 285

Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp Ser Pro

290 295 300

Asn Ser Glu Ala Ile

305

<210> 1249

<211> 311

<212>PRT

<213> Artificial Sequence

<220>

<223> chimeric protein encoded by the CC8 expression construct

<400> 1249

Met Gly Val Pro Ala Val Pro Glu Ala Ser Ser Pro Arg Trp Gly Thr

1 5 10 15

Leu Leu Leu Ala Ile Phe Leu Ala Ala Ser Arg Gly Leu Val Ala Ala

20 25 30

Phe Lys Val Thr Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Ala Thr Leu Thr Cys Arg Ile Leu Gly Pro Val Ser Lys Gly His

50 55 60

Asp Val Thr Ile Tyr Lys Thr Trp Tyr Leu Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Met Cys Ser Glu Arg Arg Pro Ile Arg Asn Leu Thr Phe Gln Asp

85 90 95

Leu His Leu His His Gly Gly His Gln Ala Ala Asn Thr Ser His Asp

100 105 110

Leu Ala Gln Arg His Gly Leu Glu Ser Ala Ser Asp His His Gly Asn

115 120 125

Phe Ser Ile Thr Met Arg Asn Leu Thr Leu Leu Asp Ser Gly Leu Tyr

130 135 140

Cys Cys Leu Val Val Glu Ile Arg His His His Ser Glu His Arg Val

145 150 155 160

His Gly Ala Met Glu Leu Gln Val Gln Thr Gly Lys Asp Ala Pro Ser

165 170 175

Asn Cys Val Val Tyr Pro Ser Ser Ser Gln Asp Ser Glu Asn Ile Thr

180 185 190

Ala Ala Ala Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu

195 200 205

Pro Leu Ile Leu Leu Leu Val Tyr Lys Gln Arg Gln Ala Ala Ser Asn

210 215 220

Arg Arg Ala Gln Glu Leu Val Arg Met Asp Ser Asn Ile Gln Gly Ile

225 230 235 240

Glu Asn Pro Gly Phe Glu Ala Ser Pro Pro Ala Gln Gly Ile Pro Glu

245 250 255

Ala Lys Val Arg His Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser

260 265 270

Glu Ser Gly Arg His Leu Leu Ser Glu Pro Ser Thr Pro Leu Ser Pro

275 280 285

Pro Gly Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp

290 295 300

Ser Pro Asn Phe Glu Val Ile

305 310

<210> 1250

<211> 310

<212>PRT

<213> Artificial Sequence

<220>

<223> chimeric protein encoded by the CC9 expression construct

<400> 1250

Met Gly Val Pro Thr Ala Leu Glu Ala Gly Ser Trp Arg Trp Gly Ser

1 5 10 15

Leu Leu Phe Ala Leu Phe Leu Ala Ala Ser Leu Gly Pro Val Ala Ala

20 25 30

Phe Lys Val Ala Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Val Thr Leu Thr Cys Arg Leu Leu Gly Pro Val Asp Lys Gly His

50 55 60

Asp Val Thr Phe Tyr Lys Thr Trp Tyr Arg Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Thr Cys Lys Glu His Arg Pro Ile Arg Asn Phe Thr Leu Gln His

85 90 95

Leu Gln His His Gly Ser His Leu Lys Ala Asn Ala Ser His Asp Gln

100 105 110

Pro Gln Lys His Gly Leu Glu Ser Ala Ser Asp His His Gly Asn Phe

115 120 125

Ser Ile Thr Met Arg Asn Leu Thr Leu Leu Asp Ser Gly Leu Tyr Cys

130 135 140

Cys Leu Val Val Glu Ile Arg His His His Ser Glu His Arg Val His

145 150 155 160

Gly Ala Met Glu Leu Gln Val Gln Thr Gly Lys Asp Ala Pro Ser Asn

165 170 175

Cys Val Val Tyr Pro Ser Ser Ser Gln Asp Ser Glu Asn Ile Thr Ala

180 185 190

Ala Ala Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu Pro

195 200 205

Leu Ile Leu Leu Leu Val Tyr Lys Gln Arg Gln Ala Ala Ser Asn Arg

210 215 220

Arg Ala Gln Glu Leu Val Arg Met Asp Ser Asn Ile Gln Gly Ile Glu

225 230 235 240

Asn Pro Gly Phe Glu Ala Ser Pro Pro Ala Gln Gly Ile Pro Glu Ala

245 250 255

Lys Val Arg His Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser Glu

260 265 270

Ser Gly Arg His Leu Leu Ser Glu Pro Ser Thr Pro Leu Ser Pro Pro

275 280 285

Gly Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp Ser

290 295 300

Pro Asn Phe Glu Val Ile

305 310

<210> 1251

<211> 310

<212>PRT

<213> Artificial Sequence

<220>

<223> chimeric protein encoded by the CC10 expression construct

<400> 1251

Met Gly Val Pro Ala Val Pro Glu Ala Ser Ser Pro Arg Trp Gly Thr

1 5 10 15

Leu Leu Leu Ala Ile Phe Leu Ala Ala Ser Arg Gly Leu Val Ala Ala

20 25 30

Phe Lys Val Thr Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Ala Thr Leu Thr Cys Arg Ile Leu Gly Pro Val Ser Lys Gly His

50 55 60

Asp Val Thr Ile Tyr Lys Thr Trp Tyr Leu Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Met Cys Ser Glu Arg Arg Pro Ile Arg Asn Leu Thr Phe Gln Asp

85 90 95

Leu His Leu His His Gly Gly His Gln Ala Ala Asn Thr Ser His Asp

100 105 110

Leu Ala Gln Arg His Gly Leu Glu Leu Ala Ser Asp His His Gly Asn

115 120 125

Phe Ser Ile Thr Leu Arg Asn Val Thr Pro Arg Asp Ser Gly Leu Tyr

130 135 140

Cys Cys Leu Val Ile Glu Leu Lys Asn His His Pro Glu Gln Arg Phe

145 150 155 160

Tyr Gly Ser Met Glu Leu Gln Val Gln Ala Gly Lys Gly Ser Gly Ser

165 170 175

Thr Cys Met Ala Ser Asn Glu Gln Asp Ser Asp Ser Ile Thr Ala Ala

180 185 190

Ala Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu Pro Leu

195 200 205

Ile Leu Leu Leu Val Tyr Lys Gln Arg Gln Val Ala Ser His Arg Arg

210 215 220

Ala Gln Glu Leu Val Arg Met Asp Ser Ser Asn Thr Gln Gly Ile Glu

225 230 235 240

Asn Pro Gly Phe Glu Thr Thr Pro Pro Phe Gln Gly Met Pro Glu Ala

245 250 255

Lys Thr Arg Pro Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser Glu

260 265 270

Ser Gly Arg Tyr Leu Leu Ser Asp Pro Ser Thr Pro Leu Ser Pro Pro

275 280 285

Gly Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp Ser

290 295 300

Pro Asn Ser Glu Ala Ile

305 310

<210> 1252

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 5B

<400> 1252

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Val

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu Glu Trp Ile

35 40 45

Gly Ile Ile Asp Thr Tyr Tyr Gly Asp Ala Thr Tyr Asn Gln Lys Phe

50 55 60

Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

100 105 110

Val Thr Val Ser Ser

115

<210> 1253

<211> 107

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 5B

<400> 1253

Asn Ile Val Met Thr Gln Thr Pro Lys Phe Leu Leu Val Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser Val Ser Asn Asp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile

35 40 45

Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly

50 55 60

Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser Thr Val Gln Ala

65 70 75 80

Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr Ser Ser Pro Arg

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1254

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 46A

<400> 1254

Gln Val Gln Leu Gln Gln Ala Gly Gly Glu Leu Val Arg Pro Gly Val

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu Glu Trp Ile

35 40 45

Gly Ile Ile Asn Thr Tyr Tyr Gly Asp Ala Thr Tyr Asn Gln Lys Phe

50 55 60

Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Gly Thr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

100 105 110

Val Thr Val Ser Ser

115

<210> 1255

<211> 107

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 46A

<400> 1255

Ser Ile Val Met Thr Gln Thr Pro Lys Phe Leu Leu Val Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser Val Ser Asn Asp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile

35 40 45

Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly

50 55 60

Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser Thr Val Gln Ala

65 70 75 80

Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr Gly Ser Pro Arg

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1256

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 97A

<400> 1256

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Val

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu Glu Trp Ile

35 40 45

Gly Val Ile Asp Thr Tyr Tyr Gly Asp Ala Ser Asn Asn Gln Lys Phe

50 55 60

Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

100 105 110

Val Thr Val Ser Ser

115

<210> 1257

<211> 107

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 97A

<400> 1257

Ser Ile Val Met Thr Gln Thr Pro Lys Phe Leu Leu Val Ser Ala Gly

1 5 10 15

Asp Arg Val Ala Ile Thr Cys Lys Ala Ser Gln Ser Val Ser Asn Asp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile

35 40 45

Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly

50 55 60

Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser Thr Val Gln Ala

65 70 75 80

Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr Gly Ser Pro Arg

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1258

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 128A

<400> 1258

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Val

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu Glu Trp Ile

35 40 45

Gly Leu Ile Asp Thr Tyr Tyr Gly Asp Ala Thr Tyr Asn His Lys Phe

50 55 60

Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Arg Thr Ala Tyr

65 70 75 80

Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

100 105 110

Val Thr Ala Ser Ser

115

<210> 1259

<211> 107

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 128A

<400> 1259

Asn Ile Ala Met Thr Gln Thr Pro Lys Phe Leu Leu Val Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser Val Ser Asn Asp

20 25 30

Ile Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Arg Leu Leu Ile

35 40 45

Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly

50 55 60

Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser Thr Val Gln Ala

65 70 75 80

Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr Ser Ser Pro Arg

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1260

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 146C

<400> 1260

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Val

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu Glu Trp Ile

35 40 45

Gly Leu Ile Asp Thr Tyr Tyr Gly Asp Ala Thr Tyr Asn His Lys Phe

50 55 60

Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Arg Thr Ala Tyr

65 70 75 80

Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

100 105 110

Val Thr Ala Ser Ser

115

<210> 1261

<211> 107

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 146C

<400> 1261

Asn Ile Ala Met Thr Gln Thr Pro Lys Phe Leu Leu Val Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser Val Ser Asn Asp

20 25 30

Ile Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Arg Leu Leu Ile

35 40 45

Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly

50 55 60

Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser Thr Val Gln Ala

65 70 75 80

Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr Ser Ser Pro Arg

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1262

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 208A

<400> 1262

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Val Arg Pro Gly Val

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Gly Met His Trp Val Lys Gln Ser His Ala Lys Ser Leu Glu Trp Ile

35 40 45

Gly Val Ile Asp Thr Tyr Tyr Gly Asp Ala Gly Tyr Asn Gln Lys Phe

50 55 60

Lys Gly Lys Ala Thr Met Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ala Arg Leu Thr Ser Glu Asp Ser Ala Ile Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser

100 105 110

Val Thr Val Ser Ser

115

<210> 1263

<211> 107

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 208A

<400> 1263

Ser Ile Val Met Thr Gln Thr Pro Lys Phe Leu Leu Val Ser Ala Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser Val Ser Asn Asp

20 25 30

Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Lys Leu Leu Ile

35 40 45

Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly

50 55 60

Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser Thr Val Gln Ala

65 70 75 80

Glu Asp Leu Ala Val Tyr Phe Cys Gln Gln Asp Tyr Ser Ser Pro Arg

85 90 95

Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1264

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 215A

<400> 1264

Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala

1 5 10 15

Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Phe Ser Phe Thr Gly Tyr

20 25 30

Thr Met Asn Trp Val Lys Gln Ser His Gly Lys Asn Leu Glu Trp Ile

35 40 45

Gly Leu Ile Ser Pro Tyr Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe

50 55 60

Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Tyr Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Ser Val Thr Val Ser Ser

115

<210> 1265

<211> 106

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 215A

<400> 1265

Gln Ile Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly

1 5 10 15

Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

Phe Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Arg Leu Leu Ile Tyr

35 40 45

Asp Thr Ser Asn Leu Ala Ser Gly Val Pro Leu Arg Phe Ser Gly Ser

50 55 60

Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Met Glu Ala Glu

65 70 75 80

Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro Phe Thr

85 90 95

Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1266

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 26A

<400> 1266

Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala

1 5 10 15

Ser Met Lys Ile Ser Cys Lys Ala Ser Gly Phe Ser Phe Thr Gly Tyr

20 25 30

Thr Met Asn Trp Val Lys Gln Ser His Val Lys Asn Leu Glu Trp Ile

35 40 45

Gly Leu Ile Ser Pro Tyr Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe

50 55 60

Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Leu Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Tyr Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Ser Val Thr Val Ser Ser

115

<210> 1267

<211> 106

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 26A

<400> 1267

Gln Ile Val Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly

1 5 10 15

Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Arg Leu Leu Ile Tyr

35 40 45

Asp Thr Ser Asn Leu Ala Ser Gly Val Pro Leu Arg Phe Ser Gly Ser

50 55 60

Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Met Glu Ala Glu

65 70 75 80

Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro Phe Thr

85 90 95

Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1268

<211> 120

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 164A

<400> 1268

Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Glu Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Tyr

20 25 30

Asn Met Asn Trp Val Lys Gln Ser Asn Gly Lys Ser Leu Glu Trp Ile

35 40 45

Gly Asn Ile Asp Pro Tyr Tyr Gly Ser Ala Ser Tyr Asn Gln Lys Phe

50 55 60

Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Thr Thr Ala Tyr

65 70 75 80

Met Gln Leu Lys Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Thr Arg Ser Asn Tyr Gly Tyr Tyr Gly Tyr Phe Asp Val Trp Gly Ala

100 105 110

Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 1269

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 164A

<400> 1269

Asn Ile Met Met Thr Gln Ser Pro Ser Ser Leu Ala Val Ser Ala Gly

1 5 10 15

Glu Lys Val Thr Met Ser Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Ser Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys His Gln

85 90 95

Phe Leu Ser Ser Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Met Lys

100 105 110

<210> 1270

<211> 108

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 164A sequence no. 2

<400> 1270

Glu Asn Val Leu Thr Gln Ser Pro Ala Ile Met Ala Ala Ser Pro Gly

1 5 10 15

Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Ser Ser

20 25 30

Asn Leu His Trp Tyr Gln Gln Lys Ser Gly Thr Ser Thr Lys Phe Trp

35 40 45

Ile Tyr Arg Thr Ser Asn Leu Ala Ser Glu Val Pro Ala Pro Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Ser Val Glu

65 70 75 80

Ala Glu Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Gly Tyr Pro

85 90 95

Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1271

<211> 120

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 230A

<400> 1271

Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Glu Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Gly Ser

20 25 30

Asn Met Asn Trp Val Lys Gln Asn Asn Gly Lys Ser Leu Glu Trp Ile

35 40 45

Gly Asn Ile Asp Pro Tyr Tyr Gly Tyr Thr Thr Tyr Asn Gln Lys Phe

50 55 60

Lys Gly Lys Ala Thr Leu Thr Val Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Gln Leu Lys Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Asp Tyr Asp Tyr Ala Leu Gly Tyr Phe Asp Val Trp Gly Ala

100 105 110

Gly Thr Thr Val Thr Val Ser Ser

115 120

<210> 1272

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 230A

<400> 1272

Asp Val Val Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly

1 5 10 15

Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser

20 25 30

Asn Gly Asn Thr Tyr Leu His Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Phe Cys Ser Gln Ser

85 90 95

Thr His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1273

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 53A

<400> 1273

Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Phe Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Tyr Ile Tyr Pro Tyr Asn Asp Gly Thr Lys Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Phe Asp Tyr Asp Thr Leu Arg Tyr Trp Gly Gln Gly Thr Thr

100 105 110

Leu Thr Val Ser Ser

115

<210> 1274

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 53A

<400> 1274

Asp Val Val Leu Thr Gln Thr Pro Leu Ser Leu Pro Val Asn Ile Gly

1 5 10 15

Asp Gln Ala Ser Ile Ser Cys Lys Ser Thr Lys Ser Leu Leu Asn Ser

20 25 30

Asp Gly Phe Thr Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Val Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Ser

85 90 95

Asn Tyr Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1275

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 259A

<400> 1275

Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Phe Met His Trp Val Lys Gln Lys Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Tyr Ile Tyr Pro Tyr Asn Asp Gly Thr Lys Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Lys Ala Thr Leu Thr Ser Asp Lys Ser Ser Ser Thr Ala Tyr

65 70 75 80

Met Asp Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Phe Asp Tyr Asp Thr Leu Arg Tyr Trp Gly Gln Gly Thr Thr

100 105 110

Leu Thr Val Ser Ser

115

<210> 1276

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 259A

<400> 1276

Asp Val Val Leu Thr Gln Thr Pro Leu Ser Leu Pro Val Asn Ile Gly

1 5 10 15

Asp Gln Ala Ser Ile Ser Cys Lys Ser Thr Lys Ser Leu Leu Asn Ser

20 25 30

Asp Gly Phe Thr Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Ile Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Ser

85 90 95

Asn Tyr Phe Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1277

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 33A

<400> 1277

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Tyr

20 25 30

Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile

35 40 45

Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Gly Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Val Tyr Trp Gly Gln Gly

100 105 110

Thr Ser Val Thr Val Ser Ser

115

<210> 1278

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 33A

<400> 1278

Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly

1 5 10 15

Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser

20 25 30

Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly

85 90 95

Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1279

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 39A

<400> 1279

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Asn

20 25 30

Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile

35 40 45

Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Ser Val Thr Val Ser Ser

115

<210> 1280

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 39A

<400> 1280

Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly

1 5 10 15

Asp Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Asn

20 25 30

Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly

85 90 95

Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1281

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 124A

<400> 1281

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser Asn

20 25 30

Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Met

35 40 45

Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Phe Trp Gly Gln Gly

100 105 110

Thr Ser Val Thr Val Ser Ser

115

<210> 1282

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 124A

<400> 1282

Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly

1 5 10 15

Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Asn

20 25 30

Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly

85 90 95

Ser His Val Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1283

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 321D

<400> 1283

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala

1 5 10 15

Ala Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Ser His

20 25 30

Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile

35 40 45

Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Asp Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Tyr Trp Gly Gln Gly

100 105 110

Thr Ser Val Thr Val Ser Ser

115

<210> 1284

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 321D

<400> 1284

Asp Val Leu Met Thr Gln Thr Pro Leu Ser Leu Pro Val Ser Leu Gly

1 5 10 15

Asp Gln Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser

20 25 30

Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Lys Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Thr Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly

85 90 95

Ser His Val Pro Phe Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1285

<211> 121

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 51A

<400> 1285

Gln Val Gln Leu Gln Gln Ser Gly Ala Glu Leu Met Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Thr Gly Tyr Thr Phe Ser Arg Tyr

20 25 30

Trp Ile Glu Trp Val Lys Gln Arg Pro Gly His Gly Leu Glu Trp Ile

35 40 45

Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Asn Glu Lys Phe

50 55 60

Lys Gly Lys Ala Thr Phe Thr Ala Asp Thr Ser Ser Asn Thr Ala Tyr

65 70 75 80

Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys

85 90 95

Ala Ser Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly Tyr Trp Gly

100 105 110

Gln Gly Thr Leu Val Thr Val Ser Ala

115 120

<210> 1286

<211> 106

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 51A

<400> 1286

Gln Ile Val Leu Ser Gln Ser Pro Ala Ile Leu Ser Ala Ser Pro Gly

1 5 10 15

Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Leu Ser Tyr Met

20 25 30

His Trp Tyr Gln Gln Arg Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr

35 40 45

Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser

50 55 60

Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu

65 70 75 80

Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Asn Pro Tyr Thr

85 90 95

Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1287

<211> 123

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 353A

<400> 1287

Glu Val Lys Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Asp Phe Ser Arg Tyr

20 25 30

Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile

35 40 45

Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Thr Pro Ser Leu

50 55 60

Lys Asp Lys Phe Ile Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Ser Lys Val Arg Tyr Glu Asp Thr Ala Leu Tyr Tyr Cys

85 90 95

Ala Arg Pro Gly Glu Ile Tyr Tyr Tyr Gly Ser Tyr Trp Phe Ala Tyr

100 105 110

Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ala

115 120

<210> 1288

<211> 111

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 353A

<400> 1288

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 Cys Arg Ala Ser Glu Ser Val Glu Tyr Tyr

20 25 30

Gly Thr Ser Leu Met Gln Trp Phe Gln Gln Lys Pro Gly Gln Pro Pro

35 40 45

Lys Leu Leu Ile Tyr Ala Ala Ser Asn Val Glu Ser Arg Val Pro Ala

50 55 60

Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Ser Leu Asn Ile His

65 70 75 80

Pro Val Glu Glu Asp Asp Ile Ala Met Tyr Phe Cys Gln Gln Ser Arg

85 90 95

Lys Asp Pro Trp Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1289

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> VH domain of murine antibody 305A

<400> 1289

Asp Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln

1 5 10 15

Ser Leu Ser Leu Thr Cys Ser Val Thr Gly Tyr Ser Ile Thr Ser Gly

20 25 30

Tyr Tyr Trp Asn Trp Ile Arg Gln Phe Pro Gly Asn Lys Leu Glu Trp

35 40 45

Met Gly Tyr Ile Ser Tyr Asp Gly Ser Asn Asn Tyr Asn Pro Ser Leu

50 55 60

Lys Asn Arg Ile Ser Ile Thr Arg Asp Thr Ser Lys Asn Gln Phe Phe

65 70 75 80

Leu Lys Leu Asn Ser Val Thr Thr Glu Asp Thr Ala Thr Tyr Tyr Cys

85 90 95

Ala Arg Arg His Asp Tyr Leu Ser Phe Ala Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Ile Val Ser Ala

115

<210> 1290

<211> 111

<212>PRT

<213> Artificial Sequence

<220>

<223> VL domain of murine antibody 305A

<400> 1290

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 Cys Lys Ala Ser Gln Ser Val Asp Tyr Asp

20 25 30

Gly Asp Ser Tyr Met Asn Trp Tyr Gln Gln Lys Pro Gly Gln Pro Pro

35 40 45

Lys Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu Ser Gly Ile 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 Gln Ser Asp

85 90 95

Glu Asp Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1291

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> h128A VH CDR1

<400> 1291

Gly Tyr Thr Phe Thr Asp Tyr Gly Met His

1 5 10

<210> 1292

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR1 according to IMGT

<400> 1292

Gly Tyr Thr Phe Thr Asp Tyr Gly

15

<210> 1293

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR1 according to Kabat

<400> 1293

Asp Tyr Gly Met His

15

<210> 1294

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR1 according to Chothia

<400> 1294

Gly Tyr Thr Phe Thr Asp Tyr

15

<210> 1295

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR1 according to Contact

<400> 1295

Thr Asp Tyr Gly Met His

15

<210> 1296

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR1 Exemplary sequence

<400> 1296

Gly Phe Ser Phe Thr Gly Tyr Thr Met Asn

1 5 10

<210> 1297

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR1 according to IMGT

<400> 1297

Gly Phe Ser Phe Thr Gly Tyr Thr

15

<210> 1298

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR1 according to Kabat

<400> 1298

Gly Tyr Thr Met Asn

15

<210> 1299

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR1 according to Chothia

<400> 1299

Gly Phe Ser Phe Thr Gly Tyr

15

<210> 1300

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR1 according to Contact

<400> 1300

Thr Gly Tyr Thr Met Asn

15

<210> 1301

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR1 exemplary sequence

<400> 1301

Gly Tyr Ser Phe Thr Gly Ser Asn Met Asn

1 5 10

<210> 1302

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR1 according to IMGT

<400> 1302

Gly Tyr Ser Phe Thr Gly Ser Asn

15

<210> 1303

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR1 according to Kabat

<400> 1303

Gly Ser Asn Met Asn

15

<210> 1304

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR1 according to Chothia

<400> 1304

Gly Tyr Ser Phe Thr Gly Ser

15

<210> 1305

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR1 according to Contact

<400> 1305

Thr Gly Ser Asn Met Asn

15

<210> 1306

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR1 exemplary sequence

<400> 1306

Gly Tyr Thr Phe Thr Ser Tyr Phe Met His

1 5 10

<210> 1307

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR1 according to IMGT

<400> 1307

Gly Tyr Thr Phe Thr Ser Tyr Phe

15

<210> 1308

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR1 according to Kabat

<400> 1308

Ser Tyr Phe Met His

15

<210> 1309

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR1 according to Chothia

<400> 1309

Gly Tyr Thr Phe Thr Ser Tyr

15

<210> 1310

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR1 according to Contact

<400> 1310

Thr Ser Tyr Phe Met His

15

<210> 1311

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A VH CDR1 exemplary sequence

<400> 1311

Gly Tyr Thr Phe Ser Ser Tyr Trp Ile Glu

1 5 10

<210> 1312

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A VH CDR1 according to IMGT

<400> 1312

Gly Tyr Thr Phe Ser Ser Tyr Trp

15

<210> 1313

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A VH CDR1 according to Kabat

<400> 1313

Ser Tyr Trp Ile Glu

15

<210> 1314

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A VH CDR1 according to Chothia

<400> 1314

Gly Tyr Thr Phe Ser Ser Tyr

15

<210> 1315

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A VH CDR1 according to Contact

<400> 1315

Ser Ser Tyr Trp Ile Glu

15

<210> 1316

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 39A VH CDR1 exemplary sequence

<400> 1316

Gly Tyr Thr Phe Ser Ser Asn Trp Ile Glu

1 5 10

<210> 1317

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 39A VH CDR1 according to IMGT

<400> 1317

Gly Tyr Thr Phe Ser Ser Asn Trp

15

<210> 1318

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> 39A VH CDR1 according to Kabat

<400> 1318

Ser Asn Trp Ile Glu

15

<210> 1319

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 39A VH CDR1 according to Chothia

<400> 1319

Gly Tyr Thr Phe Ser Ser Asn

15

<210> 1320

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 39A VH CDR1 according to Contact

<400> 1320

Ser Ser Asn Trp Ile Glu

15

<210> 1321

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D VH CDR1 exemplary sequence

<400> 1321

Gly Tyr Thr Phe Ser Ser His Trp Ile Glu

1 5 10

<210> 1322

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D VH CDR1 according to IMGT

<400> 1322

Gly Tyr Thr Phe Ser Ser His Trp

15

<210> 1323

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D VH CDR1 according to Kabat

<400> 1323

Ser His Trp Ile Glu

15

<210> 1324

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D VH CDR1 according to Chothia

<400> 1324

Gly Tyr Thr Phe Ser Ser His

15

<210> 1325

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D VH CDR1 according to Contact

<400> 1325

Ser Ser His Trp Ile Glu

15

<210> 1326

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR1 exemplary sequence

<400> 1326

Gly Phe Asp Phe Ser Arg Tyr Trp Met Asn

1 5 10

<210> 1327

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR1 according to IMGT

<400> 1327

Gly Phe Asp Phe Ser Arg Tyr Trp

15

<210> 1328

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR1 according to Kabat

<400> 1328

Arg Tyr Trp Met Asn

15

<210> 1329

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR1 according to Chothia

<400> 1329

Gly Phe Asp Phe Ser Arg Tyr

15

<210> 1330

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR1 according to Contact

<400> 1330

Ser Arg Tyr Trp Met Asn

15

<210> 1331

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR1 exemplary sequence

<400> 1331

Gly Tyr Ser Ile Thr Ser Gly Tyr Tyr Trp Asn

1 5 10

<210> 1332

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR1 according to IMGT

<400> 1332

Gly Tyr Ser Ile Thr Ser Gly Tyr Tyr

15

<210> 1333

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR1 according to Kabat

<400> 1333

Ser Gly Tyr Tyr Trp Asn

15

<210> 1334

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR1 according to Chothia

<400> 1334

Gly Tyr Ser Ile Thr Ser Gly Tyr

15

<210> 1335

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR1 according to Contact

<400> 1335

Thr Ser Gly Tyr Tyr Trp Asn

15

<210> 1336

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR2 exemplary sequence

<400> 1336

Ile Ile Asp Thr Tyr Tyr Gly Asp Ala Thr Tyr Asn Gln Lys Phe Lys

1 5 10 15

Gly

<210> 1337

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR2 according to IMGT

<400> 1337

Ile Asp Thr Tyr Tyr Gly Asp Ala

15

<210> 1338

<211> 4

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR2 according to Chothia

<400> 1338

Thr Tyr Tyr Gly

1

<210> 1339

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR2 according to Contact

<400> 1339

Trp Ile Gly Ile Ile Asp Thr Tyr Tyr Gly Asp Ala Thr

1 5 10

<210> 1340

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR2 according to AbM

<400> 1340

Ile Ile Asp Thr Tyr Tyr Gly Asp Ala Thr

1 5 10

<210> 1341

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A VH CDR2 exmeplary sequence

<400> 1341

Ile Ile Asn Thr Tyr Tyr Gly Asp Ala Thr Tyr Asn Gln Lys Phe Lys

1 5 10 15

Gly

<210> 1342

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A VH CDR2 according to IMGT

<400> 1342

Ile Asn Thr Tyr Tyr Gly Asp Ala

15

<210> 1343

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A VH CDR2 according to Contact

<400> 1343

Trp Ile Gly Ile Ile Asn Thr Tyr Tyr Gly Asp Ala Thr

1 5 10

<210> 1344

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A VH CDR2 according to AbM

<400> 1344

Ile Ile Asn Thr Tyr Tyr Gly Asp Ala Thr

1 5 10

<210> 1345

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> 97A VH CDR2 exemplary sequence

<400> 1345

Val Ile Asp Thr Tyr Tyr Gly Asp Ala Ser Asn Asn Gln Lys Phe Lys

1 5 10 15

Gly

<210> 1346

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 97A VH CDR2 according to Contact

<400> 1346

Trp Ile Gly Val Ile Asp Thr Tyr Tyr Gly Asp Ala Ser

1 5 10

<210> 1347

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 97A VH CDR2 according to AbM

<400> 1347

Val Ile Asp Thr Tyr Tyr Gly Asp Ala Ser

1 5 10

<210> 1348

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> 128A VH CDR2 exemplary sequence

<400> 1348

Leu Ile Asp Thr Tyr Tyr Gly Asp Ala Thr Tyr Asn His Lys Phe Lys

1 5 10 15

Gly

<210> 1349

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 128A VH CDR2 according to Contact

<400> 1349

Trp Ile Gly Leu Ile Asp Thr Tyr Tyr Gly Asp Ala Thr

1 5 10

<210> 1350

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 128A VH CDR2 according to AbM

<400> 1350

Leu Ile Asp Thr Tyr Tyr Gly Asp Ala Thr

1 5 10

<210> 1351

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> 108A VH CDR2 exemplary sequence

<400> 1351

Val Ile Asp Thr Tyr Tyr Gly Asp Ala Gly Tyr Asn Gln Lys Phe Lys

1 5 10 15

Gly

<210> 1352

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 208A VH CDR2 according to Contact

<400> 1352

Trp Ile Gly Val Ile Asp Thr Tyr Tyr Gly Asp Ala Gly

1 5 10

<210> 1353

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 208A VH CDR2 according to AbM

<400> 1353

Val Ile Asp Thr Tyr Tyr Gly Asp Ala Gly

1 5 10

<210> 1354

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR2 exemplary sequence

<400> 1354

Leu Ile Ser Pro Tyr Asn Gly Gly Thr Ser Tyr Asn Gln Lys Phe Lys

1 5 10 15

Gly

<210> 1355

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR2 according to IMGT

<400> 1355

Ile Ser Pro Tyr Asn Gly Gly Thr

15

<210> 1356

<211> 4

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR2 according to Chothia

<400> 1356

Pro Tyr Asn Gly

1

<210> 1357

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR2 according to Contact

<400> 1357

Trp Ile Gly Leu Ile Ser Pro Tyr Asn Gly Gly Thr Ser

1 5 10

<210> 1358

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR2 according to AbM

<400> 1358

Leu Ile Ser Pro Tyr Asn Gly Gly Thr Ser

1 5 10

<210> 1359

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VH CDR2 exemplary sequence

<400> 1359

Asn Ile Asp Pro Tyr Tyr Gly Ser Ala Ser Tyr Asn Gln Lys Phe Lys

1 5 10 15

Gly

<210> 1360

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VH CDR2 according to IMGT

<400> 1360

Ile Asp Pro Tyr Tyr Gly Ser Ala

15

<210> 1361

<211> 4

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VH CDR2 according to Chothia

<400> 1361

Pro Tyr Tyr Gly

1

<210> 1362

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VH CDR2 according to Contact

<400> 1362

Trp Ile Gly Asn Ile Asp Pro Tyr Tyr Gly Ser Ala Ser

1 5 10

<210> 1363

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VH CDR2 according to AbM

<400> 1363

Asn Ile Asp Pro Tyr Tyr Gly Ser Ala Ser

1 5 10

<210> 1364

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR2 exemplary sequence

<400> 1364

Asn Ile Asp Pro Tyr Tyr Gly Tyr Thr Thr Tyr Asn Gln Lys Phe Lys

1 5 10 15

Gly

<210> 1365

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR2 according to IMGT

<400> 1365

Ile Asp Pro Tyr Tyr Gly Tyr Thr

15

<210> 1366

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR2 according to Contact

<400> 1366

Trp Ile Gly Asn Ile Asp Pro Tyr Tyr Gly Tyr Thr Thr

1 5 10

<210> 1367

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR2 according to AbM

<400> 1367

Asn Ile Asp Pro Tyr Tyr Gly Tyr Thr Thr

1 5 10

<210> 1368

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR2 exemplary sequence

<400> 1368

Tyr Ile Tyr Pro Tyr Asn Asp Gly Thr Lys Tyr Asn Glu Lys Phe Lys

1 5 10 15

Gly

<210> 1369

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR2 according to IMGT

<400> 1369

Ile Tyr Pro Tyr Asn Asp Gly Thr

15

<210> 1370

<211> 4

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR2 according to Chothia

<400> 1370

Pro Tyr Asn Asp

1

<210> 1371

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR2 according to Contact

<400> 1371

Trp Ile Gly Tyr Ile Tyr Pro Tyr Asn Asp Gly Thr Lys

1 5 10

<210> 1372

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR2 according to AbM

<400> 1372

Tyr Ile Tyr Pro Tyr Asn Asp Gly Thr Lys

1 5 10

<210> 1373

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D VH CDR2 according to Contact

<400> 1373

Trp Ile Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Asp

1 5 10

<210> 1374

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D VH CDR2 according to AbM

<400> 1374

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asp

1 5 10

<210> 1375

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR2 exmemplary sequence

<400> 1375

Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Thr Pro Ser Leu Lys

1 5 10 15

Asp

<210> 1376

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR2 according to IMGT

<400> 1376

Ile Asn Pro Asp Ser Ser Thr Ile

15

<210> 1377

<211> 4

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR2 according to Chothia

<400> 1377

Pro Asp Ser Ser

1

<210> 1378

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR2 according to Contact

<400> 1378

Trp Ile Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn

1 5 10

<210> 1379

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR2 according to AbM

<400> 1379

Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn

1 5 10

<210> 1380

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR2 exemplary sequence

<400> 1380

Tyr Ile Ser Tyr Asp Gly Ser Asn Asn Tyr Asn Pro Ser Leu Lys Asn

1 5 10 15

<210> 1381

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR2 according to IMGT

<400> 1381

Ile Ser Tyr Asp Gly Ser Asn

15

<210> 1382

<211> 3

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR2 according to Chothia

<400> 1382

Tyr Asp Gly

1

<210> 1383

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR2 according to Contact

<400> 1383

Trp Met Gly Tyr Ile Ser Tyr Asp Gly Ser Asn Asn

1 5 10

<210> 1384

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR2 according to AbM

<400> 1384

Tyr Ile Ser Tyr Asp Gly Ser Asn Asn

15

<210> 1385

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> h128A VH CDR3

<400> 1385

Arg Ala Gly Asn Ala Met Asp Tyr

15

<210> 1386

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR3 according to IMGT

<400> 1386

Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr

1 5 10

<210> 1387

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR3 according to Chothia

<400> 1387

Ala Gly Asn Ala Met Asp

15

<210> 1388

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VH CDR3 according to Contact

<400> 1388

Ala Arg Arg Ala Gly Asn Ala Met Asp

15

<210> 1389

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A VH CDR3 exemplary sequence

<400> 1389

Arg Ala Gly Thr Ala Met Asp Tyr

15

<210> 1390

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A VH CDR3 according to IMGT

<400> 1390

Ala Arg Arg Ala Gly Thr Ala Met Asp Tyr

1 5 10

<210> 1391

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A VH CDR3 according to Chothia

<400> 1391

Ala Gly Thr Ala Met Asp

15

<210> 1392

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A VH CDR3 according to Contact

<400> 1392

Ala Arg Arg Ala Gly Thr Ala Met Asp

15

<210> 1393

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR3 exemplary sequence

<400> 1393

Arg Ala Tyr Gly Tyr Ala Met Asp Tyr

15

<210> 1394

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR3 according to IMGT

<400> 1394

Ala Arg Arg Ala Tyr Gly Tyr Ala Met Asp Tyr

1 5 10

<210> 1395

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR3 according to Chothia

<400> 1395

Ala Tyr Gly Tyr Ala Met Asp

15

<210> 1396

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VH CDR3 according to Contact

<400> 1396

Ala Arg Arg Ala Tyr Gly Tyr Ala Met Asp

1 5 10

<210> 1397

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VH CDR3 exemplary sequence

<400> 1397

Ser Asn Tyr Gly Tyr Tyr Gly Tyr Phe Asp Val

1 5 10

<210> 1398

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VH CDR3 according to IMGT

<400> 1398

Thr Arg Ser Asn Tyr Gly Tyr Tyr Gly Tyr Phe Asp Val

1 5 10

<210> 1399

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VH CDR3 according to Chothia

<400> 1399

Asn Tyr Gly Tyr Tyr Gly Tyr Phe Asp

15

<210> 1400

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VH CDR3 according to Contact

<400> 1400

Thr Arg Ser Asn Tyr Gly Tyr Tyr Gly Tyr Phe Asp

1 5 10

<210> 1401

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR3 exemplary sequence

<400> 1401

Asp Tyr Asp Tyr Ala Leu Gly Tyr Phe Asp Val

1 5 10

<210> 1402

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR3 according to IMGT

<400> 1402

Ala Arg Asp Tyr Asp Tyr Ala Leu Gly Tyr Phe Asp Val

1 5 10

<210> 1403

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR3 according to Chothia

<400> 1403

Tyr Asp Tyr Ala Leu Gly Tyr Phe Asp

15

<210> 1404

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VH CDR3 according to Contact

<400> 1404

Ala Arg Asp Tyr Asp Tyr Ala Leu Gly Tyr Phe Asp

1 5 10

<210> 1405

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223>ToBeDefined

<400> 1405

Phe Asp Tyr Asp Thr Leu Arg Tyr

15

<210> 1406

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR3 exemplary sequence

<400> 1406

Ala Arg Phe Asp Tyr Asp Thr Leu Arg Tyr

1 5 10

<210> 1407

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR3 according to IMGT

<400> 1407

Asp Tyr Asp Thr Leu Arg

15

<210> 1408

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR3 according to Chothia

<400> 1408

Ala Arg Phe Asp Tyr Asp Thr Leu Arg

15

<210> 1409

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VH CDR3 according to Contact

<400> 1409

Trp Leu Leu Tyr Tyr Tyr Ala Met Val Tyr

1 5 10

<210> 1410

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A VH CDR3 according to IMGT

<400> 1410

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Val Tyr

1 5 10

<210> 1411

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A VH CDR3 according to Chothia

<400> 1411

Leu Leu Tyr Tyr Tyr Ala Met Val

15

<210> 1412

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A VH CDR3 according to Contact

<400> 1412

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Val

1 5 10

<210> 1413

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 124A VH CDR3 exemplary sequence

<400> 1413

Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Phe

1 5 10

<210> 1414

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 124A VH CDR3 according to IMGT

<400> 1414

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Phe

1 5 10

<210> 1415

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> 51A VH CDR3 according to IMGT

<400> 1415

Ala Ser Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly Tyr

1 5 10

<210> 1416

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 51A VH CDR3 according to Contact

<400> 1416

Ala Ser Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly

1 5 10

<210> 1417

<211> 14

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR3 exemplary sequence

<400> 1417

Pro Gly Glu Ile Tyr Tyr Tyr Gly Ser Tyr Trp Phe Ala Tyr

1 5 10

<210> 1418

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR3 according to IMGT

<400> 1418

Ala Arg Pro Gly Glu Ile Tyr Tyr Tyr Gly Ser Tyr Trp Phe Ala Tyr

1 5 10 15

<210> 1419

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR3 according to Chothia

<400> 1419

Gly Glu Ile Tyr Tyr Tyr Gly Ser Tyr Trp Phe Ala

1 5 10

<210> 1420

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VH CDR3 according to Contact

<400> 1420

Ala Arg Pro Gly Glu Ile Tyr Tyr Tyr Gly Ser Tyr Trp Phe Ala

1 5 10 15

<210> 1421

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR3 exemplary sequence

<400> 1421

Arg His Asp Tyr Leu Ser Phe Ala Tyr

15

<210> 1422

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR3 according to IMGT

<400> 1422

Ala Arg Arg His Asp Tyr Leu Ser Phe Ala Tyr

1 5 10

<210> 1423

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR3 according to Chothia

<400> 1423

His Asp Tyr Leu Ser Phe Ala

15

<210> 1424

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VH CDR3 according to Contact

<400> 1424

Ala Arg Arg His Asp Tyr Leu Ser Phe Ala

1 5 10

<210> 1425

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VL CDR1 exemplary sequence

<400> 1425

Lys Ala Ser Gln Ser Val Ser Asn Asp Val Ala

1 5 10

<210> 1426

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VL CDR1 according to IMGT

<400> 1426

Gln Ser Val Ser Asn Asp

15

<210> 1427

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VL CDR1 according to Chothia

<400> 1427

Ser Gln Ser Val Ser Asn Asp

15

<210> 1428

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VL CDR1 according to Contact

<400> 1428

Ser Asn Asp Val Ala Trp Tyr

15

<210> 1429

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 128A VL CDR1 exemplary sequence

<400> 1429

Lys Ala Ser Gln Ser Val Ser Asn Asp Ile Ala

1 5 10

<210> 1430

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 128A VL CDR1 according to Contact

<400> 1430

Ser Asn Asp Ile Ala Trp Tyr

15

<210> 1431

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VL CDR1 exemplary sequence

<400> 1431

Ser Ala Ser Ser Ser Val Ser Tyr Met Phe

1 5 10

<210> 1432

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VL CDR1 according to IMGT

<400> 1432

Ser Ser Val Ser Tyr

15

<210> 1433

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VL CDR1 according to Chothia

<400> 1433

Ser Ser Ser Val Ser Tyr

15

<210> 1434

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VL CDR1 according to Contact

<400> 1434

Ser Tyr Met Phe Trp Tyr

15

<210> 1435

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 26A VL CDR1 exemplary sequence

<400> 1435

Ser Ala Ser Ser Ser Val Ser Tyr Met Tyr

1 5 10

<210> 1436

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 26A VL CDR1 according to Contact

<400> 1436

Ser Tyr Met Tyr Trp Tyr

15

<210> 1437

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR1 exemplary sequence

<400> 1437

Lys Ser Ser Gln Ser Val Leu Tyr Ser Ser Asn Gln Lys Asn Tyr Leu

1 5 10 15

Ala

<210> 1438

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR1 according to IMGT

<400> 1438

Gln Ser Val Leu Tyr Ser Ser Asn Gln Lys Asn Tyr

1 5 10

<210> 1439

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR1 according to Chothia

<400> 1439

Ser Gln Ser Val Leu Tyr Ser Ser Asn Gln Lys Asn Tyr

1 5 10

<210> 1440

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus CDRs of VH by paratope group (Fig. 18)

<220>

<221> VARIANT

<222> 1

<223> Xaa = Ile, Val or Leu

<220>

<221> VARIANT

<222> 3

<223> Xaa = Asn or Asp

<220>

<221> VARIANT

<222> 10

<223> Xaa = Thr, Ser or Gly

<220>

<221> VARIANT

<222> 11

<223> Xaa = Tyr or Asn

<220>

<221> VARIANT

<222> 13

<223> Xaa = Gln or His

<400> 1440

Xaa Ile Xaa Thr Tyr Tyr Gly Asp Ala Xaa Xaa Asn Xaa Lys Phe Lys

1 5 10 15

Gly

<210> 1441

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus CDRs of VH by paratope group (Fig. 18)

<220>

<221> VARIANT

<222> 6

<223> Xaa = Ser or Thr

<220>

<221> VARIANT

<222> 7

<223> Xaa = Tyr, Asn or His

<400> 1441

Gly Tyr Thr Phe Ser Xaa Xaa Trp Ile Glu

1 5 10

<210> 1442

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus CDRs of VH by paratope group (Fig. 18)

<220>

<221> VARIANT

<222> 10

<223> Xaa = Ser or Asp

<400> 1442

Glu Ile Leu Pro Gly Ser Gly Ser Thr Xaa Tyr Asn Glu Lys Phe Lys

1 5 10 15

Gly

<210> 1443

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> Consensus CDRs of VH by paratope group (Fig. 18)

<220>

<221> VARIANT

<222> 10

<223> Xaa = Val or Ile

<400> 1443

Lys Ala Ser Gln Ser Val Ser Asn Asp Xaa Ala

1 5 10

<210> 1444

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> Consensus CDRs of VH by paratope group (Fig. 18)

<220>

<221> VARIANT

<222> 5

<223> Xaa = Ser or Gly

<400> 1444

Gln Gln Asp Tyr Xaa Ser Pro Arg Thr

15

<210> 1445

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> Consensus CDRs of VH by paratope group (Fig. 18)

<220>

<221> VARIANT

<222> 2

<223> Xaa = Val or Ile

<400> 1445

Leu Xaa Ser Asn Arg Phe Ser

15

<210> 1446

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> Consensus CDRs of VH by paratope group (Fig. 18)

<220>

<221> VARIANT

<222> 9

<223> Xaa = Ser or Asn

<400> 1446

Arg Ser Ser Gln Ser Ile Val His Xaa Asn Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1447

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> Consensus CDRs of VH by paratope group (Fig. 18)

<220>

<221> VARIANT

<222> 2

<223> Xaa = Val or Leu

<400> 1447

Lys Xaa Ser Asn Arg Phe Ser

15

<210> 1448

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> Consensus CDRs of VH by paratope group (Fig. 18)

<220>

<221> VARIANT

<222> 6

<223> Xaa = Val or Phe

<400> 1448

Phe Gln Gly Ser His Xaa Pro Phe Thr

15

<210> 1449

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> Consensus CDRs of VH by paratope group (Fig. 18)

<400> 1449

Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Tyr

1 5 10

<210> 1450

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR1 #1 according to Contact

<400> 1450

Leu Tyr Ser Ser Asn Gln Lys Asn Tyr Leu Ala Trp Tyr

1 5 10

<210> 1451

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR1 #2 exemplary sequence

<400> 1451

Ser Ala Ser Ser Ser Val Ser Ser Ser Asn Leu His

1 5 10

<210> 1452

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR1 #2 according to IMGT

<400> 1452

Ser Ser Val Ser Ser Ser Asn

15

<210> 1453

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR1 #2 according to Chothia

<400> 1453

Ser Ser Ser Val Ser Ser Ser Asn

15

<210> 1454

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VL CDR1 exemplary sequence

<400> 1454

Arg Ser Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr Leu His

1 5 10 15

<210> 1455

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VL CDR1 according to IMGT

<400> 1455

Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr

1 5 10

<210> 1456

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VL CDR1 according to Chothia

<400> 1456

Ser Gln Ser Leu Val His Ser Asn Gly Asn Thr Tyr

1 5 10

<210> 1457

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VL CDR1 according to Contact

<400> 1457

Val His Ser Asn Gly Asn Thr Tyr Leu His Trp Tyr

1 5 10

<210> 1458

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VL CDR1 according to Kabat

<400> 1458

Lys Ser Thr Lys Ser Leu Leu Asn Ser Asp Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1459

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VL CDR1 according to IMGT

<400> 1459

Lys Ser Leu Leu Asn Ser Asp Gly Phe Thr Tyr

1 5 10

<210> 1460

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VL CDR1 according to Chothia

<400> 1460

Thr Lys Ser Leu Leu Asn Ser Asp Gly Phe Thr Tyr

1 5 10

<210> 1461

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VL CDR1 according to Contact

<400> 1461

Leu Asn Ser Asp Gly Phe Thr Tyr Leu Asp Trp Tyr

1 5 10

<210> 1462

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> 39A VL CDR1 exemplary sequence

<400> 1462

Arg Ser Ser Gln Ser Ile Val His Asn Asn Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1463

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 39A VL CDR1 according to IMGT

<400> 1463

Gln Ser Ile Val His Asn Asn Gly Asn Thr Tyr

1 5 10

<210> 1464

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 39A VL CDR1 according to Chothia

<400> 1464

Ser Gln Ser Ile Val His Asn Asn Gly Asn Thr Tyr

1 5 10

<210> 1465

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> 39A VL CDR1 according to Contact

<400> 1465

Val His Asn Asn Gly Asn Thr Tyr Leu Glu Trp Tyr

1 5 10

<210> 1466

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VL CDR1 exemplary sequence

<400> 1466

Arg Ala Ser Glu Ser Val Glu Tyr Tyr Gly Thr Ser Leu Met Gln

1 5 10 15

<210> 1467

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VL CDR1 according to IMGT

<400> 1467

Glu Ser Val Glu Tyr Tyr Gly Thr Ser Leu

1 5 10

<210> 1468

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VL CDR1 according to Chothia

<400> 1468

Ser Glu Ser Val Glu Tyr Tyr Gly Thr Ser Leu

1 5 10

<210> 1469

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VL CDR1 according to IMGT

<400> 1469

Lys Ala Ser Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr Met Asn

1 5 10 15

<210> 1470

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VL CDR1 exemplary sequence

<400> 1470

Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr

1 5 10

<210> 1471

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VL CDR1 according to Chothia

<400> 1471

Ser Gln Ser Val Asp Tyr Asp Gly Asp Ser Tyr

1 5 10

<210> 1472

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VL CDR1 according to Contact

<400> 1472

Asp Tyr Asp Gly Asp Ser Tyr Met Asn Trp Tyr

1 5 10

<210> 1473

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VL CDR2 exemplary sequence

<400> 1473

Tyr Ala Ser Asn Arg Tyr Thr

15

<210> 1474

<211> 3

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VL CDR2 according to IMGT

<400> 1474

Tyr Ala Ser

1

<210> 1475

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VL CDR2 according to Contact

<400> 1475

Leu Leu Ile Tyr Tyr Ala Ser Asn Arg Tyr

1 5 10

<210> 1476

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VL CDR2 exemplary sequence

<400> 1476

Asp Thr Ser Asn Leu Ala Ser

15

<210> 1477

<211> 3

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VL CDR2 according to IMGT

<400> 1477

Asp Thr Ser

1

<210> 1478

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VL CDR2 according to Contact

<400> 1478

Leu Leu Ile Tyr Asp Thr Ser Asn Leu Ala

1 5 10

<210> 1479

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR2 #2 exmeplary sequence

<400> 1479

Arg Thr Ser Asn Leu Ala Ser

15

<210> 1480

<211> 3

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR2 #2 according to IMGT

<400> 1480

Arg Thr Ser

1

<210> 1481

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR2 #2 according to Contact

<400> 1481

Phe Trp Ile Tyr Arg Thr Ser Asn Leu Ala

1 5 10

<210> 1482

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VL CDR2 exemplary sequence

<400> 1482

Leu Val Ser Asn Arg Phe Ser

15

<210> 1483

<211> 3

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VL CDR2 according to IMGT

<400> 1483

Leu Val Ser

1

<210> 1484

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VL CDR2 according to Contact

<400> 1484

Leu Leu Ile Tyr Leu Val Ser Asn Arg Phe

1 5 10

<210> 1485

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 259A VL CDR2 exemplary sequence

<400> 1485

Leu Ile Ser Asn Arg Phe Ser

15

<210> 1486

<211> 3

<212>PRT

<213> Artificial Sequence

<220>

<223> 259A VL CDR2 according to IMGT

<400> 1486

Leu Ile Ser

1

<210> 1487

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 259A VL CDR2 according to Contact

<400> 1487

Leu Leu Ile Tyr Leu Ile Ser Asn Arg Phe

1 5 10

<210> 1488

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VL CDR2 exemplary sequence

<400> 1488

Ala Ala Ser Asn Val Glu Ser

15

<210> 1489

<211> 3

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VL CDR2 according to IMGT

<400> 1489

Ala Ala Ser

1

<210> 1490

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VL CDR2 according to Contact

<400> 1490

Leu Leu Ile Tyr Ala Ala Ser Asn Val Glu

1 5 10

<210> 1491

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VL CDR2 exemplary sequence

<400> 1491

Ala Ala Ser Asn Leu Glu Ser

15

<210> 1492

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VL CDR2 according to Contact

<400> 1492

Leu Leu Ile Tyr Ala Ala Ser Asn Leu Glu

1 5 10

<210> 1493

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> h128A VL CDR3

<400> 1493

Gln Gln Asp Tyr Ser Ser Pro Arg Thr

15

<210> 1494

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VL CDR3 according to Chothia

<400> 1494

Asp Tyr Ser Ser Pro Arg

15

<210> 1495

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 5B VL CDR3 according to Contact

<400> 1495

Gln Gln Asp Tyr Ser Ser Pro Arg

15

<210> 1496

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A VL CDR3 according to Kabat

<400> 1496

Gln Gln Asp Tyr Gly Ser Pro Arg Thr

15

<210> 1497

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A VL CDR3 according to Chothia

<400> 1497

Asp Tyr Gly Ser Pro Arg

15

<210> 1498

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 46A VL CDR3 according to Contact

<400> 1498

Gln Gln Asp Tyr Gly Ser Pro Arg

15

<210> 1499

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VL CDR3 according to Kabat

<400> 1499

Gln Gln Trp Ser Ser Tyr Pro Phe Thr

15

<210> 1500

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VL CDR3 according to Chothia

<400> 1500

Trp Ser Ser Tyr Pro Phe

15

<210> 1501

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 215A VL CDR3 according to Contact

<400> 1501

Gln Gln Trp Ser Ser Tyr Pro Phe

15

<210> 1502

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR3 #2 according to Kabat

<400> 1502

Gln Gln Trp Ser Gly Tyr Pro Arg Thr

15

<210> 1503

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR3 #2 according to Chothia

<400> 1503

Trp Ser Gly Tyr Pro Arg

15

<210> 1504

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR3 #2 according to Contact

<400> 1504

Gln Gln Trp Ser Gly Tyr Pro Arg

15

<210> 1505

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VL CDR3 according to Kabat

<400> 1505

Ser Gln Ser Thr His Val Pro Tyr Thr

15

<210> 1506

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VL CDR3 according to Chothia

<400> 1506

Ser Thr His Val Pro Tyr

15

<210> 1507

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 230A VL CDR3 according to Contact

<400> 1507

Ser Gln Ser Thr His Val Pro Tyr

15

<210> 1508

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VL CDR3 according to Kabat

<400> 1508

Phe Gln Ser Asn Tyr Phe Pro Trp Thr

15

<210> 1509

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VL CDR3 according to Chothia

<400> 1509

Ser Asn Tyr Phe Pro Trp

15

<210> 1510

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 53A VL CDR3 according to Contact

<400> 1510

Phe Gln Ser Asn Tyr Phe Pro Trp

15

<210> 1511

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A VL CDR3 according to Kabat

<400> 1511

Phe Gln Gly Ser His Val Pro Tyr Thr

15

<210> 1512

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A VL CDR3 according to Chothia

<400> 1512

Gly Ser His Val Pro Tyr

15

<210> 1513

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 33A VL CDR3 according to Contact

<400> 1513

Phe Gln Gly Ser His Val Pro Tyr

15

<210> 1514

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D VL CDR3 according to Kabat

<400> 1514

Phe Gln Gly Ser His Val Pro Phe Thr

15

<210> 1515

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D VL CDR3 according to Chothia

<400> 1515

Gly Ser His Val Pro Phe

15

<210> 1516

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 321D VL CDR3 according to Contact

<400> 1516

Phe Gln Gly Ser His Val Pro Phe

15

<210> 1517

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VL CDR3 according to Kabat

<400> 1517

Gln Gln Ser Arg Lys Asp Pro Trp Thr

15

<210> 1518

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VL CDR3 according to Chothia

<400> 1518

Ser Arg Lys Asp Pro Trp

15

<210> 1519

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 353A VL CDR3 according to Contact

<400> 1519

Gln Gln Ser Arg Lys Asp Pro Trp

15

<210> 1520

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VL CDR3 according to Kabat

<400> 1520

Gln Gln Ser Asp Glu Asp Pro Tyr Thr

15

<210> 1521

<211> 6

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VL CDR3 according to Chothia

<400> 1521

Ser Asp Glu Asp Pro Tyr

15

<210> 1522

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 305A VL CDR3 according to Contact

<400> 1522

Gln Gln Ser Asp Glu Asp Pro Tyr

15

<210> 1523

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR3 according to Kabat

<400> 1523

His Gln Phe Leu Ser Ser Tyr Thr

15

<210> 1524

<211> 5

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR3 according to Chothia

<400> 1524

Phe Leu Ser Ser Tyr

15

<210> 1525

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR3 according to Contact

<400> 1525

His Gln Phe Leu Ser Ser Tyr

15

<210> 1526

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR2 according to Kabat

<400> 1526

Trp Ala Ser Thr Arg Glu Ser

15

<210> 1527

<211> 3

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR2 according to IMGT

<400> 1527

Trp Ala Ser

1

<210> 1528

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR2 according to Contact

<400> 1528

Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu

1 5 10

<210> 1529

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VH domain of 26A

<400> 1529

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Ser Phe Thr Gly Tyr

20 25 30

Thr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Leu Ile Ser Pro Tyr Asn Gly Gly Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Tyr Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 1530

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VH domain of 26A

<400> 1530

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Phe Ser Phe Thr Gly Tyr

20 25 30

Thr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Leu Ile Ser Pro Tyr Asn Gly Gly Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Tyr Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 1531

<211> 118

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VH domain of 26A

<400> 1531

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Phe Ser Phe Thr Gly Tyr

20 25 30

Thr Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Leu Ile Ser Pro Tyr Asn Gly Gly Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Ala Thr Leu Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Tyr Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr

100 105 110

Leu Val Thr Val Ser Ser

115

<210> 1532

<211> 106

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VL domain of 26A

<400> 1532

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

Tyr Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

35 40 45

Asp Thr Ser Asn Leu Ala Ser Gly Ile Pro Ala Arg Phe Ser Gly Ser

50 55 60

Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro Glu

65 70 75 80

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1533

<211> 106

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VL domain of 26A

<400> 1533

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Met Ser Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

Tyr Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

35 40 45

Asp Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser

50 55 60

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1534

<211> 106

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VL domain of 26A

<400> 1534

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Met Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Met Ser Cys Ser Ala Ser Ser Ser Val Ser Tyr Met

20 25 30

Tyr Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr

35 40 45

Asp Thr Ser Asn Leu Ala Ser Gly Val Pro Ala Arg Phe Ser Gly Ser

50 55 60

Gly Ser Gly Thr Asp Tyr Thr Leu Thr Ile Ser Ser Met Glu Pro Glu

65 70 75 80

Asp Phe Ala Val Tyr Tyr Cys Gln Gln Trp Ser Ser Tyr Pro Phe Thr

85 90 95

Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1535

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VH domain of 128A

<400> 1535

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Gly Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Leu Ile Asp Thr Tyr Tyr Gly Asp Ala Thr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser

115

<210> 1536

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VH domain of 128A

<400> 1536

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Gly Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Leu Ile Asp Thr Tyr Tyr Gly Asp Ala Thr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Ala Thr Met Thr Val Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser

115

<210> 1537

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VH domain of 128A

<400> 1537

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Gly Ser Gly Tyr Thr Phe Thr Asp Tyr

20 25 30

Gly Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Leu Ile Asp Thr Tyr Tyr Gly Asp Ala Thr Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Ala Thr Met Thr Val Asp Lys Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Arg Ala Gly Asn Ala Met Asp Tyr Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser

115

<210> 1538

<211> 107

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VL domain of 128A

<400> 1538

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser Val Ser Asn Asp

20 25 30

Ile Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asp Tyr Ser Ser Pro Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1539

<211> 107

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VL domain of 128A

<400> 1539

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser Val Ser Asn Asp

20 25 30

Ile Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Val Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asp Tyr Ser Ser Pro Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1540

<211> 107

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VL domain of 128A

<400> 1540

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Val Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Ser Val Ser Asn Asp

20 25 30

Ile Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Tyr Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Tyr Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Val Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Asp Tyr Ser Ser Pro Arg

85 90 95

Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105

<210> 1541

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VH domain of 124A

<400> 1541

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Ser Asn

20 25 30

Trp Ile Glu Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Phe Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 1542

<211> 119

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VH domain of 124A

<400> 1542

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Ser Asn

20 25 30

Trp Ile Glu Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Ala Thr Phe Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Trp Leu Leu Tyr Tyr Tyr Ala Met Asp Phe Trp Gly Gln Gly

100 105 110

Thr Leu Val Thr Val Ser Ser

115

<210> 1543

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VH domain of 259A

<400> 1543

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Phe Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Tyr Ile Tyr Pro Tyr Asn Asp Gly Thr Lys Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Phe Asp Tyr Asp Thr Leu Arg Tyr Trp Gly Gln Gly Thr Leu

100 105 110

Val Thr Val Ser Ser

115

<210> 1544

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VH domain of 259A

<400> 1544

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Phe Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Tyr Ile Tyr Pro Tyr Asn Asp Gly Thr Lys Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Ala Thr Leu Thr Ser Asp Thr Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Phe Asp Tyr Asp Thr Leu Arg Tyr Trp Gly Gln Gly Thr Leu

100 105 110

Leu Thr Val Ser Ser

115

<210> 1545

<211> 117

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VH domain of 259A

<400> 1545

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Phe Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile

35 40 45

Gly Tyr Ile Tyr Pro Tyr Asn Asp Gly Thr Lys Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Ala Thr Leu Thr Ser Asp Lys Ser Thr Ser Thr Ala Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg Phe Asp Tyr Asp Thr Leu Arg Tyr Trp Gly Gln Gly Thr Leu

100 105 110

Leu Thr Val Ser Ser

115

<210> 1546

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VL domain of 124A

<400> 1546

Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Asn

20 25 30

Asn Gly Asn Thr Tyr Leu Glu Trp Phe Gln Gln Arg Pro Gly Gln Ser

35 40 45

Pro Arg Arg Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln Gly

85 90 95

Ser His Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1547

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VL domain of 124A

<400> 1547

Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Asn

20 25 30

Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln Ser

35 40 45

Pro Arg Leu Leu Ile Tyr Lys Val Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Gly

85 90 95

Ser His Val Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1548

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VL domain of 259A

<400> 1548

Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Lys Ser Thr Lys Ser Leu Leu Asn Ser

20 25 30

Asp Gly Phe Thr Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Ile Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln Ser

85 90 95

Asn Tyr Phe Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1549

<211> 112

<212>PRT

<213> Artificial Sequence

<220>

<223> humanized VL domain of 259A

<400> 1549

Asp Ile Val Leu Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Lys Ser Thr Lys Ser Leu Leu Asn Ser

20 25 30

Asp Gly Phe Thr Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Ile Ser Asn Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Leu Gly Val Tyr Tyr Cys Phe Gln Ser

85 90 95

Asn Tyr Phe Pro Trp Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys

100 105 110

<210> 1550

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR1

<400> 1550

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser

20 25

<210> 1551

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR1

<400> 1551

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Met Lys Val Ser Cys Lys Ala Ser

20 25

<210> 1552

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR1

<400> 1552

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala

1 5 10 15

Ser Met Lys Val Ser Cys Lys Ala Ser

20 25

<210> 1553

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR1

<400> 1553

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Ala Ser

20 25

<210> 1554

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR1

<400> 1554

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Met Lys Ile Ser Cys Lys Ala Ser

20 25

<210> 1555

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR1

<400> 1555

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala

1 5 10 15

Ser Met Lys Ile Ser Cys Lys Ala Ser

20 25

<210> 1556

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH CDR2

<400> 1556

Leu Ile Ser Pro Tyr Gln Gly Gly Thr Ser

1 5 10

<210> 1557

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH CDR2

<400> 1557

Leu Ile Ser Pro Tyr Ser Gly Gly Thr Ser

1 5 10

<210> 1558

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH CDR2

<400> 1558

Leu Ile Ser Pro Tyr Ala Gly Gly Thr Ser

1 5 10

<210> 1559

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH CDR2

<400> 1559

Leu Ile Ser Pro Tyr Asp Gly Gly Thr Ser

1 5 10

<210> 1560

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR3

<400> 1560

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1561

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR3

<400> 1561

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1562

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR3

<400> 1562

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1563

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR3

<400> 1563

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1564

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR3

<400> 1564

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1565

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR3

<400> 1565

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1566

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR3

<400> 1566

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1567

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VH FR3

<400> 1567

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1568

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1568

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1569

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1569

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1570

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1570

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1571

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1571

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1572

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1572

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1573

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1573

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1574

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1574

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1575

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1575

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1576

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1576

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1577

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1577

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1578

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1578

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1579

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1579

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1580

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1580

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1581

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1581

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1582

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1582

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1583

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1583

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1584

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1584

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1585

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1585

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1586

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1586

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1587

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1587

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1588

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1588

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1589

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1589

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1590

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1590

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1591

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1591

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1592

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1592

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1593

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1593

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1594

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1594

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1595

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1595

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1596

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1596

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1597

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1597

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1598

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1598

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1599

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1599

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1600

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1600

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1601

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1601

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1602

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1602

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1603

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1603

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1604

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1604

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1605

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1605

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1606

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1606

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1607

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1607

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1608

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1608

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1609

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1609

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1610

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1610

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1611

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1611

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1612

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1612

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1613

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1613

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1614

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VH FR3

<400> 1614

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1615

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VL FR1

<400> 1615

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys

20

<210> 1616

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1616

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Met Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys

20

<210> 1617

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1617

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys

20

<210> 1618

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1618

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Leu Ser Cys

20

<210> 1619

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1619

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Met Ser Cys

20

<210> 1620

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1620

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Met Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys

20

<210> 1621

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1621

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Met Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Leu Ser Cys

20

<210> 1622

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1622

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Met Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Met Ser Cys

20

<210> 1623

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1623

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Leu Ser Cys

20

<210> 1624

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1624

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Met Ser Cys

20

<210> 1625

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1625

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Met Ser Cys

20

<210> 1626

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1626

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Met Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Leu Ser Cys

20

<210> 1627

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1627

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Met Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Met Ser Cys

20

<210> 1628

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1628

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Met Ser Cys

20

<210> 1629

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR1

<400> 1629

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Met Ser Ala Ser Pro Gly

1 5 10 15

Glu Arg Val Thr Met Ser Cys

20

<210> 1630

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VL CDR2

<400> 1630

Asp Thr Ser Gln Leu Ala Ser

15

<210> 1631

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL CDR2

<400> 1631

Asp Thr Ser Ser Leu Ala Ser

15

<210> 1632

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL CDR2

<400> 1632

Asp Thr Ser Ala Leu Ala Ser

15

<210> 1633

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL CDR2

<400> 1633

Asp Thr Ser Asp Leu Ala Ser

15

<210> 1634

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> h26A VL FR3

<400> 1634

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1635

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1635

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1636

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1636

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1637

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1637

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Met Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1638

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1638

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Ala Ala Val Tyr Tyr Cys

20 25 30

<210> 1639

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1639

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1640

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1640

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Met Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1641

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1641

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Ala Ala Val Tyr Tyr Cys

20 25 30

<210> 1642

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1642

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Ser Met Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1643

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1643

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Ala Ala Val Tyr Tyr Cys

20 25 30

<210> 1644

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1644

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Met Glu Pro Glu Asp Ala Ala Val Tyr Tyr Cys

20 25 30

<210> 1645

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1645

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Ser Met Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys

20 25 30

<210> 1646

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1646

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Ala Ala Val Tyr Tyr Cys

20 25 30

<210> 1647

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1647

Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Ser Met Glu Pro Glu Asp Ala Ala Val Tyr Tyr Cys

20 25 30

<210> 1648

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H26A VL FR3

<400> 1648

Gly Val Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Thr

1 5 10 15

Leu Thr Ile Ser Ser Met Glu Pro Glu Asp Ala Ala Val Tyr Tyr Cys

20 25 30

<210> 1649

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> h128A VH FR1

<400> 1649

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Gly Ser

20 25

<210> 1650

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR1

<400> 1650

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Gly Ser

20 25

<210> 1651

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR1

<400> 1651

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Gly Ser

20 25

<210> 1652

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR1

<400> 1652

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Ile Ser Cys Lys Gly Ser

20 25

<210> 1653

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1653

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1654

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1654

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1655

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1655

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1656

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1656

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1657

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1657

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1658

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1658

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1659

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1659

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1660

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1660

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1661

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1661

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1662

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1662

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1663

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1663

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1664

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1664

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1665

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1665

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1666

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1666

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1667

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1667

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1668

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1668

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1669

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1669

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1670

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1670

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1671

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1671

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1672

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1672

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1673

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1673

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1674

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1674

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Arg Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1675

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1675

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ile Tyr Tyr Cys Ala Arg

35

<210> 1676

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1676

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1677

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1677

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ala Tyr Tyr Cys Ala Arg

35

<210> 1678

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1678

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ala Tyr Tyr Cys Ala Arg

35

<210> 1679

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR3

<400> 1679

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Val Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Ala Tyr Tyr Cys Ala Arg

35

<210> 1680

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VH FR4

<400> 1680

Trp Gly Gln Gly Thr Leu Val Thr Ala Ser Ser

1 5 10

<210> 1681

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR1

<400> 1681

Lys Ala Ser Gln Ser Val Ser Gln Asp Ile Ala

1 5 10

<210> 1682

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR1

<400> 1682

Lys Ala Ser Gln Ser Val Ser Ser Asp Ile Ala

1 5 10

<210> 1683

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR1

<400> 1683

Lys Ala Ser Gln Ser Val Ser Ala Asp Ile Ala

1 5 10

<210> 1684

<211> 11

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR1

<400> 1684

Lys Ala Ser Gln Ser Val Ser Asp Asp Ile Ala

1 5 10

<210> 1685

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR2

<400> 1685

Tyr Ala Ser Gln Arg Tyr Thr

15

<210> 1686

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR2

<400> 1686

Tyr Ala Ser Ser Arg Tyr Thr

15

<210> 1687

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR2

<400> 1687

Tyr Ala Ser Ala Arg Tyr Thr

15

<210> 1688

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR2

<400> 1688

Tyr Ala Ser Asp Arg Tyr Thr

15

<210> 1689

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1689

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

20 25 30

<210> 1690

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1690

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

20 25 30

<210> 1691

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1691

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys

20 25 30

<210> 1692

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1692

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

20 25 30

<210> 1693

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1693

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Val Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

20 25 30

<210> 1694

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1694

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Leu Ala Thr Tyr Tyr Cys

20 25 30

<210> 1695

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1695

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys

20 25 30

<210> 1696

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1696

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Val Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

20 25 30

<210> 1697

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1697

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Leu Ala Thr Tyr Tyr Cys

20 25 30

<210> 1698

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1698

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys

20 25 30

<210> 1699

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1699

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Val Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys

20 25 30

<210> 1700

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1700

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Leu Ala Thr Tyr Phe Cys

20 25 30

<210> 1701

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1701

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Val Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys

20 25 30

<210> 1702

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1702

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Leu Ala Thr Tyr Tyr Cys

20 25 30

<210> 1703

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1703

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys

20 25 30

<210> 1704

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1704

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Val Gln Pro Glu Asp Leu Ala Thr Tyr Tyr Cys

20 25 30

<210> 1705

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1705

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Val Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys

20 25 30

<210> 1706

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1706

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Leu Ala Thr Tyr Phe Cys

20 25 30

<210> 1707

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1707

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Val Gln Pro Glu Asp Leu Ala Thr Tyr Tyr Cys

20 25 30

<210> 1708

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1708

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Val Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys

20 25 30

<210> 1709

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1709

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Val Gln Pro Glu Asp Leu Ala Thr Tyr Phe Cys

20 25 30

<210> 1710

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1710

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Val Gln Pro Glu Asp Leu Ala Thr Tyr Tyr Cys

20 25 30

<210> 1711

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1711

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Val Gln Pro Glu Asp Phe Ala Thr Tyr Phe Cys

20 25 30

<210> 1712

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1712

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Leu Thr Ile Ser Ser Val Gln Pro Glu Asp Leu Ala Thr Tyr Phe Cys

20 25 30

<210> 1713

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1713

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Val Gln Pro Glu Asp Leu Ala Thr Tyr Phe Cys

20 25 30

<210> 1714

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H128A VL CDR3

<400> 1714

Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Tyr Gly Thr Asp Phe Thr

1 5 10 15

Phe Thr Ile Ser Ser Val Gln Pro Glu Asp Leu Ala Thr Tyr Phe Cys

20 25 30

<210> 1715

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR1

<400> 1715

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Ile Lys Val Ser Cys Lys Ala Ser

20 25

<210> 1716

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR1

<400> 1716

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Met Lys Pro Gly Ala

1 5 10 15

Ser Ile Lys Val Ser Cys Lys Ala Ser

20 25

<210> 1717

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH CDR1

<400> 1717

Gly Tyr Thr Phe Ser Ser Gln Trp Ile Glu

1 5 10

<210> 1718

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH CDR1

<400> 1718

Gly Tyr Thr Phe Ser Ser Ser Trp Ile Glu

1 5 10

<210> 1719

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH CDR1

<400> 1719

Gly Tyr Thr Phe Ser Ser Ala Trp Ile Glu

1 5 10

<210> 1720

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH CDR1

<400> 1720

Gly Tyr Thr Phe Ser Ser Asp Trp Ile Glu

1 5 10

<210> 1721

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1721

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Phe Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1722

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1722

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1723

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1723

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Phe Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1724

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1724

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1725

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1725

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Phe Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1726

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1726

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1727

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1727

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Phe Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1728

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1728

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Phe Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1729

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1729

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1730

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1730

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Phe Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1731

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1731

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1732

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1732

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Phe Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1733

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1733

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Phe Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1734

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1734

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1735

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1735

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Phe Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1736

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1736

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Phe Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1737

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1737

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1738

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1738

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Phe Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1739

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1739

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Phe Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1740

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1740

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Phe Thr Arg Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1741

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1741

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1742

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VH FR3

<400> 1742

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Phe Thr Ala Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1743

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL FR1

<400> 1743

Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys

20

<210> 1744

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1744

Arg Ser Ser Gln Ser Ile Val His Gln Asn Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1745

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1745

Arg Ser Ser Gln Ser Ile Val His Ala Asn Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1746

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1746

Arg Ser Ser Gln Ser Ile Val His Asp Asn Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1747

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1747

Arg Ser Ser Gln Ser Ile Val His Asn Gln Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1748

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1748

Arg Ser Ser Gln Ser Ile Val His Asn Ser Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1749

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1749

Arg Ser Ser Gln Ser Ile Val His Asn Ala Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1750

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1750

Arg Ser Ser Gln Ser Ile Val His Asn Asn Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1751

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1751

Arg Ser Ser Gln Ser Ile Val His Asn Asn Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1752

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1752

Arg Ser Ser Gln Ser Ile Val His Asn Asn Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1753

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1753

Arg Ser Ser Gln Ser Ile Val His Asn Asn Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1754

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1754

Arg Ser Ser Gln Ser Ile Val His Gln Gln Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1755

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1755

Arg Ser Ser Gln Ser Ile Val His Gln Ser Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1756

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1756

Arg Ser Ser Gln Ser Ile Val His Gln Ala Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1757

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1757

Arg Ser Ser Gln Ser Ile Val His Gln Asn Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1758

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1758

Arg Ser Ser Gln Ser Ile Val His Gln Asn Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1759

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1759

Arg Ser Ser Gln Ser Ile Val His Gln Asn Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1760

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1760

Arg Ser Ser Gln Ser Ile Val His Gln Asn Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1761

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1761

Arg Ser Ser Gln Ser Ile Val His Ala Gln Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1762

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1762

Arg Ser Ser Gln Ser Ile Val His Ala Ser Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1763

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1763

Arg Ser Ser Gln Ser Ile Val His Ala Ala Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1764

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1764

Arg Ser Ser Gln Ser Ile Val His Ala Asn Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1765

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1765

Arg Ser Ser Gln Ser Ile Val His Ala Asn Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1766

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1766

Arg Ser Ser Gln Ser Ile Val His Ala Asn Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1767

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1767

Arg Ser Ser Gln Ser Ile Val His Ala Asn Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1768

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1768

Arg Ser Ser Gln Ser Ile Val His Asp Gln Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1769

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1769

Arg Ser Ser Gln Ser Ile Val His Asp Ser Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1770

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1770

Arg Ser Ser Gln Ser Ile Val His Asp Ala Gly Asn Thr Tyr Leu Glu

1 5 10 15

<210> 1771

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1771

Arg Ser Ser Gln Ser Ile Val His Asp Asn Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1772

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1772

Arg Ser Ser Gln Ser Ile Val His Asp Asn Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1773

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1773

Arg Ser Ser Gln Ser Ile Val His Asp Asn Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1774

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1774

Arg Ser Ser Gln Ser Ile Val His Asp Asn Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1775

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1775

Arg Ser Ser Gln Ser Ile Val His Asn Gln Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1776

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1776

Arg Ser Ser Gln Ser Ile Val His Asn Gln Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1777

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1777

Arg Ser Ser Gln Ser Ile Val His Asn Gln Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1778

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1778

Arg Ser Ser Gln Ser Ile Val His Asn Gln Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1779

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1779

Arg Ser Ser Gln Ser Ile Val His Asn Ser Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1780

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1780

Arg Ser Ser Gln Ser Ile Val His Asn Ser Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1781

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1781

Arg Ser Ser Gln Ser Ile Val His Asn Ser Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1782

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1782

Arg Ser Ser Gln Ser Ile Val His Asn Ser Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1783

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1783

Arg Ser Ser Gln Ser Ile Val His Asn Ala Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1784

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1784

Arg Ser Ser Gln Ser Ile Val His Asn Ala Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1785

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1785

Arg Ser Ser Gln Ser Ile Val His Asn Ala Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1786

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1786

Arg Ser Ser Gln Ser Ile Val His Asn Ala Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1787

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1787

Arg Ser Ser Gln Ser Ile Val His Gln Gln Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1788

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1788

Arg Ser Ser Gln Ser Ile Val His Ala Gln Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1789

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1789

Arg Ser Ser Gln Ser Ile Val His Asp Gln Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1790

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1790

Arg Ser Ser Gln Ser Ile Val His Gln Ser Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1791

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1791

Arg Ser Ser Gln Ser Ile Val His Gln Ala Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1792

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1792

Arg Ser Ser Gln Ser Ile Val His Ala Ser Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1793

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1793

Arg Ser Ser Gln Ser Ile Val His Ala Ala Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1794

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1794

Arg Ser Ser Gln Ser Ile Val His Asp Ser Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1795

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1795

Arg Ser Ser Gln Ser Ile Val His Asp Ala Gly Gln Thr Tyr Leu Glu

1 5 10 15

<210> 1796

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1796

Arg Ser Ser Gln Ser Ile Val His Gln Gln Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1797

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1797

Arg Ser Ser Gln Ser Ile Val His Ala Gln Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1798

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1798

Arg Ser Ser Gln Ser Ile Val His Asp Gln Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1799

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1799

Arg Ser Ser Gln Ser Ile Val His Gln Ser Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1800

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1800

Arg Ser Ser Gln Ser Ile Val His Gln Ala Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1801

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1801

Arg Ser Ser Gln Ser Ile Val His Ala Ser Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1802

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1802

Arg Ser Ser Gln Ser Ile Val His Ala Ala Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1803

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1803

Arg Ser Ser Gln Ser Ile Val His Asp Ser Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1804

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1804

Arg Ser Ser Gln Ser Ile Val His Asp Ala Gly Ser Thr Tyr Leu Glu

1 5 10 15

<210> 1805

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1805

Arg Ser Ser Gln Ser Ile Val His Gln Gln Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1806

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1806

Arg Ser Ser Gln Ser Ile Val His Ala Gln Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1807

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1807

Arg Ser Ser Gln Ser Ile Val His Asp Gln Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1808

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1808

Arg Ser Ser Gln Ser Ile Val His Gln Ser Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1809

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1809

Arg Ser Ser Gln Ser Ile Val His Gln Ala Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1810

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1810

Arg Ser Ser Gln Ser Ile Val His Ala Ser Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1811

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1811

Arg Ser Ser Gln Ser Ile Val His Ala Ala Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1812

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1812

Arg Ser Ser Gln Ser Ile Val His Asp Ser Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1813

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1813

Arg Ser Ser Gln Ser Ile Val His Asp Ala Gly Ala Thr Tyr Leu Glu

1 5 10 15

<210> 1814

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1814

Arg Ser Ser Gln Ser Ile Val His Gln Gln Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1815

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1815

Arg Ser Ser Gln Ser Ile Val His Ala Gln Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1816

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1816

Arg Ser Ser Gln Ser Ile Val His Asp Gln Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1817

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1817

Arg Ser Ser Gln Ser Ile Val His Gln Ser Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1818

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1818

Arg Ser Ser Gln Ser Ile Val His Gln Ala Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1819

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1819

Arg Ser Ser Gln Ser Ile Val His Ala Ser Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1820

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1820

Arg Ser Ser Gln Ser Ile Val His Ala Ala Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1821

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1821

Arg Ser Ser Gln Ser Ile Val His Asp Ser Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1822

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL CDR1

<400> 1822

Arg Ser Ser Gln Ser Ile Val His Asp Ala Gly Asp Thr Tyr Leu Glu

1 5 10 15

<210> 1823

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL FR2

<400> 1823

Trp Phe Gln Gln Arg Pro Gly Gln Ser Pro Arg Arg Leu Ile Tyr

1 5 10 15

<210> 1824

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL FR2

<400> 1824

Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro Arg Arg Leu Ile Tyr

1 5 10 15

<210> 1825

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL FR2

<400> 1825

Trp Phe Gln Gln Arg Pro Gly Gln Ser Pro Arg Leu Leu Ile Tyr

1 5 10 15

<210> 1826

<211> 15

<212>PRT

<213> Artificial Sequence

<220>

<223> H124A VL FR2

<400> 1826

Trp Tyr Gln Gln Arg Pro Gly Gln Ser Pro Arg Leu Leu Ile Tyr

1 5 10 15

<210> 1827

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR1

<400> 1827

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Met Ser Cys Lys Ala Ser

20 25

<210> 1828

<211> 25

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR1

<400> 1828

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Val Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Met Ser Cys Lys Ala Ser

20 25

<210> 1829

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1829

Tyr Ile Tyr Pro Tyr Gln Asp Gly Thr Lys

1 5 10

<210> 1830

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1830

Tyr Ile Tyr Pro Tyr Ser Asp Gly Thr Lys

1 5 10

<210> 1831

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1831

Tyr Ile Tyr Pro Tyr Ala Asp Gly Thr Lys

1 5 10

<210> 1832

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1832

Tyr Ile Tyr Pro Tyr Asp Asp Gly Thr Lys

1 5 10

<210> 1833

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1833

Tyr Ile Tyr Pro Tyr Asn Glu Gly Thr Lys

1 5 10

<210> 1834

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1834

Tyr Ile Tyr Pro Tyr Asn Ser Gly Thr Lys

1 5 10

<210> 1835

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1835

Tyr Ile Tyr Pro Tyr Asn Ala Gly Thr Lys

1 5 10

<210> 1836

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1836

Tyr Ile Tyr Pro Tyr Gln Glu Gly Thr Lys

1 5 10

<210> 1837

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1837

Tyr Ile Tyr Pro Tyr Gln Ser Gly Thr Lys

1 5 10

<210> 1838

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1838

Tyr Ile Tyr Pro Tyr Gln Ala Gly Thr Lys

1 5 10

<210> 1839

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1839

Tyr Ile Tyr Pro Tyr Ser Glu Gly Thr Lys

1 5 10

<210> 1840

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1840

Tyr Ile Tyr Pro Tyr Ser Ser Gly Thr Lys

1 5 10

<210> 1841

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1841

Tyr Ile Tyr Pro Tyr Ser Ala Gly Thr Lys

1 5 10

<210> 1842

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1842

Tyr Ile Tyr Pro Tyr Ala Glu Gly Thr Lys

1 5 10

<210> 1843

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1843

Tyr Ile Tyr Pro Tyr Ala Ser Gly Thr Lys

1 5 10

<210> 1844

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1844

Tyr Ile Tyr Pro Tyr Ala Ala Gly Thr Lys

1 5 10

<210> 1845

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1845

Tyr Ile Tyr Pro Tyr Asp Glu Gly Thr Lys

1 5 10

<210> 1846

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1846

Tyr Ile Tyr Pro Tyr Asp Ser Gly Thr Lys

1 5 10

<210> 1847

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH CDR2

<400> 1847

Tyr Ile Tyr Pro Tyr Asp Ala Gly Thr Lys

1 5 10

<210> 1848

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1848

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1849

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1849

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1850

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1850

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1851

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1851

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1852

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1852

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1853

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1853

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1854

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1854

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1855

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1855

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1856

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1856

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1857

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1857

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1858

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1858

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1859

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1859

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1860

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1860

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1861

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1861

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1862

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1862

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1863

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1863

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1864

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1864

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1865

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1865

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1866

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1866

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1867

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1867

Tyr Asn Gln Lys Phe Gln Gly Arg Val Thr Met Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1868

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1868

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1869

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1869

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1870

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1870

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Met Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1871

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1871

Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Leu Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1872

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1872

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1873

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1873

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Phe Asp Thr Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1874

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1874

Tyr Ala Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1875

<211> 39

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VH FR3

<400> 1875

Tyr Asn Gln Lys Phe Gln Gly Arg Ala Thr Leu Thr Phe Asp Lys Ser

1 5 10 15

Thr Ser Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr

20 25 30

Ala Val Tyr Tyr Cys Ala Arg

35

<210> 1876

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL FR1

<400> 1876

Asp Ile Val Leu Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys

20

<210> 1877

<211> 23

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL FR1

<400> 1877

Asp Val Val Leu Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys

20

<210> 1878

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1878

Lys Ser Thr Lys Ser Leu Leu Gln Ser Asp Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1879

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1879

Lys Ser Thr Lys Ser Leu Leu Ser Ser Asp Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1880

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1880

Lys Ser Thr Lys Ser Leu Leu Ala Ser Asp Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1881

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1881

Lys Ser Thr Lys Ser Leu Leu Asp Ser Asp Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1882

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1882

Lys Ser Thr Lys Ser Leu Leu Asn Ser Glu Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1883

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1883

Lys Ser Thr Lys Ser Leu Leu Asn Ser Ser Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1884

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1884

Lys Ser Thr Lys Ser Leu Leu Asn Ser Ala Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1885

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1885

Lys Ser Thr Lys Ser Leu Leu Gln Ser Glu Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1886

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1886

Lys Ser Thr Lys Ser Leu Leu Gln Ser Ser Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1887

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1887

Lys Ser Thr Lys Ser Leu Leu Gln Ser Ala Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1888

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1888

Lys Ser Thr Lys Ser Leu Leu Ser Ser Glu Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1889

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1889

Lys Ser Thr Lys Ser Leu Leu Ser Ser Ser Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1890

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1890

Lys Ser Thr Lys Ser Leu Leu Ser Ser Ala Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1891

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1891

Lys Ser Thr Lys Ser Leu Leu Ala Ser Glu Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1892

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1892

Lys Ser Thr Lys Ser Leu Leu Ala Ser Ser Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1893

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1893

Lys Ser Thr Lys Ser Leu Leu Ala Ser Ala Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1894

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1894

Lys Ser Thr Lys Ser Leu Leu Asp Ser Glu Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1895

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1895

Lys Ser Thr Lys Ser Leu Leu Asp Ser Ser Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1896

<211> 16

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR1

<400> 1896

Lys Ser Thr Lys Ser Leu Leu Asp Ser Ala Gly Phe Thr Tyr Leu Asp

1 5 10 15

<210> 1897

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR2

<400> 1897

Leu Ile Ser Gln Arg Phe Ser

15

<210> 1898

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR2

<400> 1898

Leu Ile Ser Ser Arg Phe Ser

15

<210> 1899

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR2

<400> 1899

Leu Ile Ser Ala Arg Phe Ser

15

<210> 1900

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL CDR2

<400> 1900

Leu Ile Ser Asp Arg Phe Ser

15

<210> 1901

<211> 32

<212>PRT

<213> Artificial Sequence

<220>

<223> H259A VL FR3

<400> 1901

Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr

1 5 10 15

Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Leu Tyr Tyr Cys

20 25 30

<210> 1902

<211> 98

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGHV1-46*01 heavy chain

<400> 1902

Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala

1 5 10 15

Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr

20 25 30

Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met

35 40 45

Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe

50 55 60

Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr

65 70 75 80

Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg

<210> 1903

<211> 98

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGHV3-74*01 heavy chain

<400> 1903

Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly

1 5 10 15

Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr

20 25 30

Trp Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Val Trp Val

35 40 45

Ser Arg Ile Asn Ser Asp Gly Ser Ser Thr Ser Tyr Ala Asp Ser Val

50 55 60

Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr

65 70 75 80

Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys

85 90 95

Ala Arg

<210> 1904

<211> 99

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGHV4-61*01 heavy chain

<400> 1904

Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu

1 5 10 15

Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly

20 25 30

Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu

35 40 45

Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser

50 55 60

Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe

65 70 75 80

Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr

85 90 95

Cys Ala Arg

<210> 1905

<211> 101

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGKV2-28*01 light chain

<400> 1905

Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly

1 5 10 15

Glu Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asn Gly Tyr Asn Tyr Leu Asp Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Leu Gly Ser Asn Arg Ala Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Ala

85 90 95

Leu Gln Thr Pro Pro

100

<210> 1906

<211> 101

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGKV2-29*02 light chain

<400> 1906

Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Lys Ser Ser Gln Ser Leu Leu His Ser

20 25 30

Asp Gly Lys Thr Tyr Leu Tyr Trp Tyr Leu Gln Lys Pro Gly Gln Ser

35 40 45

Pro Gln Leu Leu Ile Tyr Glu Val Ser Ser Arg Phe Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly

85 90 95

Ile His Leu Pro Pro

100

<210> 1907

<211> 96

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGKV1-39*01 light chain

<400> 1907

Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly

1 5 10 15

Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr

20 25 30

Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile

35 40 45

Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro

65 70 75 80

Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Pro

85 90 95

<210> 1908

<211> 97

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGKV3-20*01 light chain

<400> 1908

Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

Pro

<210> 1909

<211> 97

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGKV3D-20*01 light chain

<400> 1909

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Gly Ala Ser Gln Ser Val Ser Ser Ser

20 25 30

Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Leu Ala Pro Arg Leu Leu

35 40 45

Ile Tyr Asp Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser

50 55 60

Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu

65 70 75 80

Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro

85 90 95

Pro

<210> 1910

<211> 96

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGKV3-11*01 light chain

<400> 1910

Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly

1 5 10 15

Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr

20 25 30

Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile

35 40 45

Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly

50 55 60

Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro

65 70 75 80

Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro

85 90 95

<210> 1911

<211> 101

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGKV2-30*01 light chain

<400> 1911

Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val Tyr Ser

20 25 30

Asp Gly Asn Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly Gln Ser

35 40 45

Pro Arg Arg Leu Ile Tyr Lys Val Ser Asn Arg Asp Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly

85 90 95

Thr His Trp Pro Pro

100

<210> 1912

<211> 101

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGKV2-30*02 light chain

<400> 1912

Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly

1 5 10 15

Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val His Ser

20 25 30

Asp Gly Asn Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly Gln Ser

35 40 45

Pro Arg Arg Leu Ile Tyr Lys Val Ser Asn Arg Asp Ser Gly Val Pro

50 55 60

Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile

65 70 75 80

Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gln Gly

85 90 95

Thr His Trp Pro Pro

100

<210> 1913

<211> 102

<212>PRT

<213> Artificial Sequence

<220>

<223> Human germlineIMGT IGKV4-1*01 light chain

<400> 1913

Asp Ile Val Met Thr Gln Ser Pro Asp Ser Leu Ala Val Ser Leu Gly

1 5 10 15

Glu Arg Ala Thr Ile Asn Cys Lys Ser Ser Gln Ser Val Leu Tyr Ser

20 25 30

Ser Asn Asn Lys Asn Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln

35 40 45

Pro Pro Lys Leu Leu Ile Tyr Trp Ala Ser Thr Arg Glu Ser Gly Val

50 55 60

Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr

65 70 75 80

Ile Ser Ser Leu Gln Ala Glu Asp Val Ala Val Tyr Tyr Cys Gln Gln

85 90 95

Tyr Tyr Ser Thr Pro Pro

100

<210> 1914

<211> 193

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus of human and mouse C10orf54 protein

<220>

<221> misc_feature

<222> (5)..(5)

<223> Xaa = Thr or Ala

<220>

<221> misc_feature

<222> (6)..(6)

<223> Xaa = Ala or Val

<220>

<221> misc_feature

<222> (7)..(7)

<223> Xaa = Leu or Pro

<220>

<221> misc_feature

<222> (10)..(10)

<223> Xaa =

<220>

<221> misc_feature

<222> (12)..(12)

<223> Xaa = Gly or Ser

<220>

<221> misc_feature

<222> (16)..(16)

<223> Xaa = Trp or Pro

<220>

<221> misc_feature

<222> (19)..(19)

<223> Xaa = Phe or Leu

<220>

<221> misc_feature

<222> (21)..(21)

<223> Xaa = Leu or Ile

<220>

<221> misc_feature

<222> (27)..(27)

<223> Xaa = Leu or Arg

<220>

<221> misc_feature

<222> (29)..(29)

<223> Xaa = Pro or Leu

<220>

<221> misc_feature

<222> (36)..(36)

<223> Xaa = Ala or Thr

<220>

<221> misc_feature

<222> (50)..(50)

<223> Xaa = Val or Ala

<220>

<221> misc_feature

<222> (56)..(56)

<223> Xaa = Leu or Ile

<220>

<221> misc_feature

<222> (61)..(61)

<223> Xaa = Asp or Ser

<220>

<221> misc_feature

<222> (68)..(68)

<223> Xaa = Phe or Ile

<220>

<221> misc_feature

<222> (74)..(74)

<223> Xaa = Arg or Leu

<220>

<221> misc_feature

<222> (82)..(82)

<223> Xaa = Thr or Met

<220>

<221> misc_feature

<222> (84)..(84)

<223> Xaa = Ser or Lys

<220>

<221> misc_feature

<222> (86)..(86)

<223> Xaa = Arg or His

<220>

<221> misc_feature

<222> (92),(94)

<223> Xaa = Leu or Phe

<220>

<221> misc_feature

<222> (96)..(96)

<223> Xaa = Asp or His

<220>

<221> misc_feature

<222> (98)..(98)

<223> Xaa = His or Gln

<220>

<221> misc_feature

<222> (99)..(99)

<223> Xaa = Leu or none

<220>

<221> misc_feature

<222> (103)..(103)

<223> Xaa = Gly or Ser

<220>

<221> misc_feature

<222> (105)..(105)

<223> Xaa = Gln or Leu

<220>

<221> misc_feature

<222> (106)..(106)

<223> Xaa = Ala or Lys

<220>

<221> misc_feature

<222> (109)..(109)

<223> Xaa = Thr or Ala

<220>

<221> misc_feature

<222> (113)..(113)

<223> Xaa = Leu or Gln

<220>

<221> misc_feature

<222> (114)..(114)

<223> Xaa = Ala or Pro

<220>

<221> misc_feature

<222> (116)..(116)

<223> Xaa = Arg or Lys

<220>

<221> misc_feature

<222> (121)..(121)

<223> Xaa = Ser or Leu

<220>

<221> misc_feature

<222> (133)..(133)

<223> Xaa = Met or Leu

<220>

<221> misc_feature

<222> (136)..(136)

<223> Xaa = Leu or Val

<220>

<221> misc_feature

<222> (138)..(138)

<223> Xaa = Leu or Pro

<220>

<221> misc_feature

<222> (139)..(139)

<223> Xaa = Leu or Arg

<220>

<221> misc_feature

<222> (149)..(149)

<223> Xaa = Val or Ile

<220>

<221> misc_feature

<222> (151)..(151)

<223> Xaa = Ile or Leu

<220>

<221> misc_feature

<222> (152)..(152)

<223> Xaa = Arg or Lys

<220>

<221> misc_feature

<222> (153)..(153)

<223> Xaa = His or Asn

<220>

<221> misc_feature

<222> (156)..(156)

<223> Xaa = Ser or Pro

<220>

<221> misc_feature

<222> (158)..(158)

<223> Xaa = His or Gln

<220>

<221> misc_feature

<222> (160)..(160)

<223> Xaa = Val or Phe

<220>

<221> misc_feature

<222> (161)..(161)

<223> Xaa = His or Tyr

<220>

<221> misc_feature

<222> (163)..(163)

<223> Xaa = Ala or Ser

<220>

<221> misc_feature

<222> (170)..(170)

<223> Xaa = Thr or Ala

<220>

<221> misc_feature

<222> (173)..(173)

<223> Xaa = Asp or Gly

<220>

<221> misc_feature

<222> (174)..(174)

<223> Xaa = Al aor Ser

<220>

<221> misc_feature

<222> (175)..(175)

<223> Xaa = Pro or Gly

<220>

<221> misc_feature

<222> (177)..(177)

<223> Xaa = Asn or Thr

<220>

<221> misc_feature

<222> (179)..(179)

<223> Xaa = Val or Met

<220>

<221> misc_feature

<222> (180)..(180)

<223> Xaa = Val or Ala

<220>

<221> misc_feature

<222> (181)..(181)

<223> Xaa = Tyr or none

<220>

<221> misc_feature

<222> (182)..(182)

<223> Xaa = Pro or none

<220>

<221> misc_feature

<222> (184)..(184)

<223> Xaa = Ser or Asn

<220>

<221> misc_feature

<222> (185)..(185)

<223> Xaa = Ser or Glu

<220>

<221> misc_feature

<222> (189)..(189)

<223> Xaa = Glu or Asp

<220>

<221> misc_feature

<222> (190)..(190)

<223> Xaa = Asn or Ser

<400> 1914

Met Gly Val Pro Xaa Xaa Xaa Glu Ala Xaa Ser Xaa Arg Trp Gly Xaa

1 5 10 15

Leu Leu Xaa Ala Xaa Phe Leu Ala Ala Ser Xaa Gly Xaa Val Ala Ala

20 25 30

Phe Lys Val Xaa Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Xaa Thr Leu Thr Cys Arg Xaa Leu Gly Pro Val Xaa Lys Gly His

50 55 60

Asp Val Thr Xaa Tyr Lys Thr Trp Tyr Xaa Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Xaa Cys Xaa Glu Xaa Arg Pro Ile Arg Asn Xaa Thr Xaa Gln Xaa

85 90 95

Leu Xaa Xaa His His Gly Xaa His Xaa Xaa Ala Asn Xaa Ser His Asp

100 105 110

Xaa Xaa Gln Xaa His Gly Leu Glu Xaa Ala Ser Asp His His Gly Asn

115 120 125

Phe Ser Ile Thr Xaa Arg Asn Xaa Thr Xaa Xaa Asp Ser Gly Leu Tyr

130 135 140

Cys Cys Leu Val Xaa Glu Xaa Xaa Xaa His His Xaa Glu Xaa Arg Xaa

145 150 155 160

Xaa Gly Xaa Met Glu Leu Gln Val Gln Xaa Gly Lys Xaa Xaa Xaa Ser

165 170 175

Xaa Cys Xaa Xaa Xaa Xaa Ser Xaa Xaa Gln Asp Ser Xaa Xaa Ile Thr

180 185 190

Ala

<210> 1915

<211> 8

<212>PRT

<213> Artificial Sequence

<220>

<223> 164A VL CDR1 #2 according to Contact

<400> 1915

Ser Ser Ser Asn Leu His Trp Tyr

15

<210> 1916

<211> 417

<212> DNA

<213> Artificial Sequence

<220>

<223> 230A heavy chain variable region with signal sequence

<400> 1916

atgggatgga cctggatctt tattttaatc ctgtcagtaa ctacaggtgt ccactctgag 60

gtccagctgc agcagtctgg acctgagctg gagaagcctg gcgcttcagt gaagatatcc 120

tgcaaggctt ctggttactc attcactggc tccaacatga actgggtgaa gcagaacaat 180

ggaaagagcc ttgagtggat tggaaatatt gatccttact atggttatac tacctacaac 240

cagaagttca agggcaaggc cacattgact gtagacaaat cctccagcac agcctacatg 300

cagctcaaga gcctgacatc tgaggactct gcagtctatt actgtgcaag agactatgat 360

tacgccctcg ggtacttcga tgtctggggc gcagggacca cggtcaccgt ctcctca 417

<210> 1917

<211> 13

<212>PRT

<213> Artificial Sequence

<220>

<223> 124A VH CDR2 according to Contact

<400> 1917

Trp Met Gly Glu Ile Leu Pro Gly Ser Gly Ser Thr Ser

1 5 10

<210> 1918

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus CDRs of VH by paratope group (Fig. 18)

<400> 1918

Gly Tyr Thr Phe Ser Arg Tyr Trp Ile Glu

1 5 10

<210> 1919

<211> 17

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus CDRs of VH by paratope group (Fig. 18)

<400> 1919

Glu Ile Leu Pro Gly Ser Gly Ser Thr Asn Tyr Asn Glu Lys Phe Lys

1 5 10 15

Gly

<210> 1920

<211> 12

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus CDRs of VH by paratope group (Fig. 18)

<400> 1920

Glu Glu Val Tyr Asp Gly Tyr Pro Trp Phe Gly Tyr

1 5 10

<210> 1921

<211> 10

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus CDRs of VH by paratope group (Fig. 18)

<400> 1921

Arg Ala Ser Ser Ser Leu Ser Tyr Met His

1 5 10

<210> 1922

<211> 7

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus CDRs of VH by paratope group (Fig. 18)

<400> 1922

Ala Thr Ser Asn Leu Ala Ser

15

<210> 1923

<211> 9

<212>PRT

<213> Artificial Sequence

<220>

<223> consensus CDRs of VH by paratope group (Fig. 18)

<400> 1923

Gln Gln Trp Ser Ser Asn Pro Tyr Thr

15

<---

Claims (29)

1. An isolated antibody or antigen-binding fragment thereof that binds to C10orf54 proteins, where the antibody is an antibody containing: - a heavy chain variable domain containing the following three CDRs, respectively, CDR-H1 having the sequence of SEQ ID NO: 1302, CDR-H2 having the sequence of SEQ ID NO: 1365, and CDR-H3 having the sequence of SEQ ID NO: : 1402; And - a light chain variable domain containing the following three CDRs, respectively, CDR-L1 having the sequence of SEQ ID NO: 1455, CDR-L2 having the sequence of SEQ ID NO: 1103, and CDR-L3 having the sequence of SEQ ID NO: : 1505. 2. The isolated antibody or antigen-binding fragment thereof according to claim 1, wherein the antibody contains a heavy chain variable domain containing the sequence of SEQ ID NO: 1271, and a light chain variable domain containing the sequence of SEQ ID NO: 1272. 3. An isolated antibody or antigen-binding fragment thereof according to claim 1 or 2, where the antibody is a monoclonal antibody. 4. An isolated antibody or an antigen-binding fragment thereof according to any one of paragraphs. 1-3, where the antibody is humanized. 5. Antibody or antigen-binding fragment thereof according to any one of paragraphs. 1-4, where the antigen binding fragment is a Fab fragment, F(ab') ₂ fragment, single chain Fv (sFv), diabody, tribody or mini-antibody. 6. A conjugate for detection of the C10orf54 protein, containing an antibody or its antigen-binding fragment according to any one of paragraphs. 1-5 and a detectable agent, wherein the antibody is conjugated or recombinantly fused to the detectable agent. 7. The conjugate of claim 6, wherein the detectable agent is selected from the group consisting of an enzyme, a fluorescent compound, a bioluminescent compound, a chemiluminescent compound, a radioactive isotope, a prosthetic group, a positron-emitting metal, and a non-radioactive paramagnetic metal ion. 8. Conjugate according to claim 7, where - the enzyme is selected from the group consisting of horseradish peroxidase, alkaline phosphatase, beta-galactosidase and acetylcholinesterase, - the fluorescent compound is selected from the group consisting of umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, fluorescein dichlorotriazinylamine, dansyl chloride and phycoerythrin, - the bioluminescent compound is selected from the group consisting of luciferase, luciferin and aequorin, - the chemiluminescent compound is luminol, or - radioactive isotope selected from the group consisting of ¹³¹ I, ¹²⁵ I, ^{123 I} and ¹²¹ I, ¹⁴ C, ³⁵ S, ³ H, ¹¹⁵ In, ¹¹³ In, 112 In and ¹¹¹ In, ⁹⁹ Tc, ²⁰¹ Ti, ⁶⁸ Ga , ⁶⁷ Ga, ¹⁰³ Pd, ⁹⁹ Mo, ¹³³ Xe, ¹⁸ F, ¹⁵³ Sm, ¹⁷⁷ Lu, ¹⁵⁹ Gd, ¹⁴⁹ Pm, ¹⁴⁰ La, ¹⁷⁵ Yb, ¹⁶⁶ Ho, ⁹⁰ Y, ⁴⁷ Sc, ¹⁸⁶ Re, ¹⁸⁸ Re, ¹⁴² Pr, ¹⁰⁵ Rh, ⁹⁷ Ru, ⁶⁸ Ge, ⁵⁷ Co, ⁶⁵ Zn, ⁸⁵ Sr, ³² P, ¹⁵³ Gd, ¹⁶⁹ Yb, ⁵¹ Cr, ⁵⁴ Mn, ⁷⁵ Se, ¹¹³ Sn and ¹¹⁷ Sn. 9. A polynucleotide encoding an antibody to C10orf54, containing a nucleotide sequence encoding an antibody or an antigen-binding fragment according to any one of claims. 1-5. 10. An expression vector containing the polynucleotide according to claim 9. 11. A host cell producing an antibody to C10orf54, containing the expression vector of claim 10. 12. A method for producing an antibody or an antigen-binding fragment thereof according to any one of claims. 1-5, comprising the step of culturing the host cell according to claim 11 under conditions that promote antibody production. 13. A method for detecting the C10orf54 protein in a sample in vitro, including bringing the sample into contact with an antibody or its antigen-binding fragment according to any one of claims. 1-5 or with a conjugate according to any one of paragraphs. 6-8. 14. A method for detecting or diagnosing in vitro a C10orf54-mediated disease in a subject, comprising: (a) determining the level of C10orf54 antigen in cells or a tissue sample of the subject using the antibody or antigen-binding fragment thereof according to any one of claims. 1-5 or a conjugate according to any one of paragraphs. 6-8, and (b) comparing the level of C10orf54 antigen with the level of antigen in tissue samples from a patient who does not have C10orf54-mediated disease, wherein an increase in the assayed level of C10orf54 antigen compared to the level of antigen in a tissue sample from a patient who does not have a C10orf54-mediated disease indicates the presence of a C10orf54-mediated disease. 15. The method of claim 14, wherein the level of the C10orf54 antigen is determined by a method selected from the group consisting of: immunohistochemical analysis, enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), and fluorescence-activated cell sorting (FACS). 16. A method for monitoring C10orf54-mediated disease in vitro, comprising repeating the method of claim 14 or 15 one month, six months, or one year after the initial diagnosis of C10orf54-mediated disease. 17. Method according to any one of paragraphs. 14-16, wherein the C10orf54-mediated disease is a proliferative disorder, cancer, tumorigenesis, or graft-versus-host disease. 18. A kit for detection of C10orf54 in a sample, containing an antibody or an antigen-binding fragment according to any one of paragraphs. 1-5 or a conjugate according to any one of paragraphs. 6-8, in one or more containers. 19. The kit of claim 18 further comprising substantially isolated C10orf54 antigen, preferably wherein the antigen is attached to a solid support.