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    Humanized alpha-enolase specific antibodies and methods of uses in cancer therapy
    1.
    发明授权
    Humanized alpha-enolase specific antibodies and methods of uses in cancer therapy 有权
    人源化α-烯醇酶特异性抗体及其在癌症治疗中的应用方法

    公开(公告)号：US09527922B2

    公开(公告)日：2016-12-27

    申请号：US14588212

    申请日：2014-12-31

    申请人： Development Center for Biotechnology ,  DCB-USA LLC ,  National Health Research Institutes

    发明人： Shih-Chong Tsai ,  Ta-Tung Yuan ,  Shih-Chi Tseng ,  Jiann-Shiun Lai ,  Chia-Cheng Wu ,  Chao-Yang Huang ,  Ya-Wei Tsai ,  Ying-Yung Lok ,  Chung-Hsiun Wu ,  Neng-Yao Shih ,  Ko-Jiunn Liu ,  Li-Tzong Chen

    IPC分类号： A61K39/395 ,  C07K16/40 ,  A61K39/00

    CPC分类号： C07K16/40 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/732 ,  C07K2317/76 ,  C07K2317/92

    摘要： A humanized antibody, or a binding fragment thereof, wherein the humanized antibody binds human ENO1 (GenBank: AAH50642.1), wherein the antibody comprises a light chain variable region (VL) domain comprising a CDR1 having the amino acid sequence LCDR1 (RASENIYSYLT; SEQ ID NO: 6) and a CDR2 having the amino acid sequence LCDR2 (NAKTLPE; SEQ ID NO: 7) and a CDR3 having the amino acid sequence LCDR3 (QHHYGTPYT; SEQ ID NO: 8) and an antibody heavy chain variable region (VH) domain comprising a CDR1 having the amino acid sequence HCDR1 (GYTFTSCVMN; SEQ ID NO: 3), a CDR2 having the amino acid sequence HCDR2 (YINPYNDGTKYNEKFKG; SEQ ID NO: 4) and a CDR3 having the amino acid sequence HCDR3 (EGFYYGNFDN; SEQ ID NO: 5), wherein framework regions in the light chain variable region (VL) domain and the heavy chain variable region (VH) domain comprise amino acid sequences from a human immunoglobulin.

    摘要翻译： 人源化抗体或其结合片段，其中所述人源化抗体结合人ENO1（GenBank：AAH50642.1），其中所述抗体包含轻链可变区（VL）结构域，其包含具有氨基酸序列LCDR1（RASENIYSYLT; SEQ ID NO：6）和具有氨基酸序列LCDR2（NAKTLPE; SEQ ID NO：7）的CDR2和具有氨基酸序列LCDR3（QHHYGTPYT; SEQ ID NO：8）和抗体重链可变区（ VH）结构域，其包含具有氨基酸序列HCDR1（GYTFTSCVMN; SEQ ID NO：3）的CDR1，具有氨基酸序列HCDR2（YINPYNDGTKYNEKFKG; SEQ ID NO：4）的CDR2和具有氨基酸序列HCDR3（EGFYYGNFDN ; SEQ ID NO：5），其中轻链可变区（VL）结构域和重链可变区（VH）结构域中的构架区包含来自人免疫球蛋白的氨基酸序列。

    HUMANIZED ALPHA-ENOLASE SPECIFIC ANTIBODIES AND METHODS OF USES IN CANCER THERAPY
    2.
    发明申请
    HUMANIZED ALPHA-ENOLASE SPECIFIC ANTIBODIES AND METHODS OF USES IN CANCER THERAPY 有权
    人类ALPHA-ENOLASE特异性抗体及其在癌症治疗中的使用方法

    公开(公告)号：US20160185876A1

    公开(公告)日：2016-06-30

    申请号：US14588212

    申请日：2014-12-31

    申请人： Development Center for Biotechnology ,  DCB-USA LLC ,  National Health Research Institutes

    发明人： Shih-Chong Tsai ,  Ta-Tung Yuan ,  Shih-Chi Tseng ,  Jiann-Shiun Lai ,  Chia-Cheng Wu ,  Chao-Yang Huang ,  Ya-Wei Tsai ,  Ying-Yung Lok ,  Chung-Hsiun Wu ,  Neng-Yao Shih ,  Ko-Jiunn Liu ,  Li-Tzong Chen

    IPC分类号： C07K16/40

    CPC分类号： C07K16/40 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/732 ,  C07K2317/76 ,  C07K2317/92

    摘要： A humanized antibody, or a binding fragment thereof, wherein the humanized antibody binds human ENO1 (GenBank: AAH50642.1), wherein the antibody comprises a light chain variable region (VL) domain comprising a CDR1 having the amino acid sequence LCDR1 (RASENIYSYLT; SEQ ID NO: 6) and a CDR2 having the amino acid sequence LCDR2 (NAKTLPE; SEQ ID NO: 7) and a CDR3 having the amino acid sequence LCDR3 (QHHYGTPYT; SEQ ID NO: 8) and an antibody heavy chain variable region (VH) domain comprising a CDR1 having the amino acid sequence HCDR1 (GYTFTSCVMN; SEQ ID NO: 3), a CDR2 having the amino acid sequence HCDR2 (YINPYNDGTKYNEKFKG; SEQ ID NO: 4) and a CDR3 having the amino acid sequence HCDR3 (EGFYYGNFDN; SEQ ID NO: 5), wherein framework regions in the light chain variable region (VL) domain and the heavy chain variable region (VH) domain comprise amino acid sequences from a human immunoglobulin.

    摘要翻译： 人源化抗体或其结合片段，其中所述人源化抗体结合人ENO1（GenBank：AAH50642.1），其中所述抗体包含轻链可变区（VL）结构域，其包含具有氨基酸序列LCDR1（RASENIYSYLT; SEQ ID NO：6）和具有氨基酸序列LCDR2（NAKTLPE; SEQ ID NO：7）的CDR2和具有氨基酸序列LCDR3（QHHYGTPYT; SEQ ID NO：8）和抗体重链可变区（ VH）结构域，其包含具有氨基酸序列HCDR1（GYTFTSCVMN; SEQ ID NO：3）的CDR1，具有氨基酸序列HCDR2（YINPYNDGTKYNEKFKG; SEQ ID NO：4）的CDR2和具有氨基酸序列HCDR3（EGFYYGNFDN ; SEQ ID NO：5），其中轻链可变区（VL）结构域和重链可变区（VH）结构域中的构架区包含来自人免疫球蛋白的氨基酸序列。

    ALPHA-ENOLASE SPECIFIC ANTIBODIES AND METHODS OF USES IN CANCER THERAPY
    4.
    发明申请
    ALPHA-ENOLASE SPECIFIC ANTIBODIES AND METHODS OF USES IN CANCER THERAPY 有权
    ALPHA-ENOLASE特异性抗体及其在癌症治疗中的使用方法

    公开(公告)号：US20150183884A1

    公开(公告)日：2015-07-02

    申请号：US14142186

    申请日：2013-12-27

    申请人： NATIONAL HEALTH RESEARCH INSTITUTES ,  DEVELOPMENT CENTER FOR BIOTECHNOLOGY

    发明人： Shih-Chong Tsai ,  Neng-Yao Shih ,  Ta-Tung Yuan ,  Ko-Jiunn Liu ,  Shih-Chi Tseng ,  Chih-Yung Hu ,  Hsin-Yun Wang ,  Li-Tzong Chen

    IPC分类号： C07K16/40 ,  G01N33/574

    CPC分类号： C07K16/40 ,  A61K2039/505 ,  C07K2317/34 ,  C07K2317/55 ,  C07K2317/73 ,  C07K2317/76 ,  C07K2317/92 ,  G01N33/57492 ,  G01N2333/988

    摘要： The present invention discloses an anti-human alpha-enolase (ENO1) antibody, which can bind the peptides, comprising amino-acid sequence 296FD Q D D W G A W Q K F TA309 (SEQ ID: #9) and/or 326K R I A K A V N EK S336 (SEQ ID: #10) of human ENO1 protein (GenBank: AAH50642.1), has a favorable binding activity (the binding affinity is around 2.19×10-10 mol/L) and a remarkable capability to inhibit the cell invasion and tumor metastasis of a varied of tumors. The recognized peptides and antibody of the invention are useful for diagnosis, prognosis, and treatment of cancers that have been reported to express cell-surface ENO1 such as including lung, breast, pancreas, liver, colorectal, prostate cancers and solid tumors.

    摘要翻译： 本发明公开了可以结合肽的抗人α-烯醇酶（ENO1）抗体，其包含氨基酸序列296FD QDDWGAWQKF TA309（SEQ ID：＃9）和/或326K RIAKAVN EK S336（SEQ ID＃＃10 ）的人类ENO1蛋白（GenBank：AAH50642.1）具有良好的结合活性（结合亲和力约为2.19×10 -10 mol / L），并且具有显着的抑制多种肿瘤细胞侵袭和肿瘤转移的能力 。 公认的本发明的肽和抗体可用于已经报道表达细胞表面ENO1的癌症的诊断，预后和治疗，所述癌症包括肺，乳腺，胰腺，肝脏，结肠直肠癌，前列腺癌和实体瘤。

    BISPECIFIC T-CELL ACTIVATOR ANTIBODY
    7.
    发明申请
    BISPECIFIC T-CELL ACTIVATOR ANTIBODY 有权
    双重T细胞激活剂抗体

    公开(公告)号：US20130165629A1

    公开(公告)日：2013-06-27

    申请号：US13720573

    申请日：2012-12-19

    申请人： Development Center for Biotechnology ,  DCB-USA LLC

    发明人： Yu-Shen Hsu ,  Show-Shan Sheu ,  Mingi Chang ,  Ming-Chuan Chang ,  Ta-Tung Yuan

    IPC分类号： C07K16/46 ,  C07K7/06 ,  C07K7/08

    CPC分类号： C07K16/468 ,  C07K7/06 ,  C07K7/08 ,  C07K16/2809 ,  C07K16/2887 ,  C07K2317/53 ,  C07K2317/622 ,  C07K2317/64 ,  C07K2317/732 ,  C07K2317/74 ,  C07K2317/94

    摘要： This invention relates to bispecific antibodies having combinations of linker and hinge sequences to create linker-hinge interface domains with biological significance. Such linker-hinge interface domains covalently join two molecules, maintain the biological activities of linked molecules (target binding), stabilize the biological characteristics of new molecule (solubility and 4° C. stability), maintain the chemical, biochemical and physical properties (cytotoxicity) of the linked molecules, and modulate the biological characteristics of the linked molecules (activating T-lymphocytes without significant sign of proliferations). Both linker (GGGGS) and hinge (CPPCP) sequences are required to establish functional linker-hinge interface domains as deletion of any of the component resulted in significant lost of T-lymphocyte mediated activity.

    摘要翻译： 本发明涉及具有接头和铰链序列组合的双特异性抗体以产生具有生物学意义的接头 - 铰链界面结构域。 这种接头 - 铰链界面域共价连接两个分子，保持连接分子的生物活性（靶结合），稳定新分子的生物学特性（溶解度和4℃稳定性），保持化学，生化和物理性质（细胞毒性 ），并调节连接分子的生物学特性（活化T淋巴细胞而没有显着增殖迹象）。 需要两种接头（GGGGS）和铰链（CPPCP）序列来建立功能性接头 - 铰链界面区域，因为任何组分的缺失导致T淋巴细胞介导的活性的显着丧失。

    ALPHA-ENOLASE SPECIFIC ANTIBODIES AND METHOD OF USE IN IMMUNE DISEASES
    10.
    发明申请
    ALPHA-ENOLASE SPECIFIC ANTIBODIES AND METHOD OF USE IN IMMUNE DISEASES 有权
    ALPHA-ENOLASE特异性抗体及其在免疫疾病中的使用方法

    公开(公告)号：US20150175710A1

    公开(公告)日：2015-06-25

    申请号：US14580127

    申请日：2014-12-22

    申请人： DEVELOPMENT CENTER FOR BIOTECHNOLOGY

    发明人： Shih-Chong Tsai ,  Mingl Chang ,  Ta-Tung Yuan ,  Shih-Chi Tseng ,  Shyi-Jou Chen ,  Wei-Tso Chia ,  Hsin-Yun Wang

    IPC分类号： C07K16/40 ,  A61K39/39 ,  A61K39/395

    CPC分类号： A61K39/39 ,  A61K39/3955 ,  A61K2039/505 ,  B63B1/121 ,  B63B15/02 ,  B63B2001/123 ,  B63B2015/005 ,  B63H9/08 ,  C07K16/40 ,  C07K2317/34 ,  C07K2317/76 ,  C07K2317/92

    摘要： A method for treating an inflammatory disease or an immune disorder includes administering to a subject in need of such treatment an antagonist against ENO1. The antagonist binds ENO1 and inhibits ENO1 plasminogen receptor activity. The antagonist may be an anti-human ENO1 antibody, or an scFv, Fab, or F(ab)2 fragment thereof, that specifically binds to human ENO1 (GenBank: AAH50642.1) for the treatment of an inflammatory disease or an immune disorder, which may be multiple sclerosis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, systemic Lupus erythematosus, chronic obstructive pulmonary disease (COPD), asthma, allergy, psoriasis, type 1 diabetes mellitus, artherosclerosis or osteoporosis.

    摘要翻译： 用于治疗炎性疾病或免疫疾病的方法包括向需要这种治疗的受试者施用针对ENO1的拮抗剂。 拮抗剂结合ENO1并抑制ENO1纤溶酶原受体活性。 拮抗剂可以是特异性结合人ENO1（GenBank：AAH50642.1）用于治疗炎性疾病或免疫疾病的抗人ENO1抗体或其scFv，Fab或F（ab）2片段） ，可能是多发性硬化症，类风湿性关节炎，克罗恩病，溃疡性结肠炎，系统性红斑狼疮，慢性阻塞性肺病（COPD），哮喘，过敏，牛皮癣，1型糖尿病，动脉粥样硬化或骨质疏松症。