公开(公告)号：US10138300B2

公开(公告)日：2018-11-27

申请号：US15640935

申请日：2017-07-03

Applicant: DEVELOPMENT CENTER FOR BIOTECHNOLOGY

Inventor： Jiann-Shiun Lai ,  Li-Shuang Ai ,  Yan-Da Lai ,  Yen-Yu Wu ,  Yi-San Tsai ,  Yi-Jiue Tsai ,  Juo-Yu Huang ,  Cheng-Chou Yu ,  Chuan-Lung Hsu ,  Chien-Tsun Kuan ,  Szu-Liang Lai ,  Li-Ya Wang

IPC: C07K16/28 ,  C07K16/30 ,  G01N33/74 ,  A61K51/10 ,  A61K31/4439 ,  C07K14/71 ,  C07K16/00 ,  A61K47/68 ,  A61K47/48 ,  A61K39/00

Abstract: The present invention relates to an antibody or antigen-binding fragment thereof that bind human vascular endothelial growth factor receptor 2 (VEGFR-2). The present invention also relates to a method for inhibiting VEGFR-2-mediated signaling in a subject in need, a method for treating diseases and/or disorders caused by or related to VEGFR-2 activity and/or signaling in a subject afflicted with the diseases and disorders, a method for treating tumor in a subject afflicted with the tumor, a method for inhibiting cell proliferation of endothelial cells in a subject in need, and a method for detecting human vascular endothelial growth factor receptor in a sample.

公开(公告)号：US20180208561A1

公开(公告)日：2018-07-26

申请号：US15326490

申请日：2015-06-15

Applicant: Development Center for Biotechnology ,  DCB-USA LLC

Inventor： Nan-Horng Lin ,  Chu-Bin Liao ,  Shao-Zheng Peng ,  Shih-Chieh Yen ,  Mann-Yan Kuo

IPC: C07D241/44 ,  A61P35/00 ,  A61P3/10 ,  A61P13/12 ,  A61P9/00 ,  A61P19/02 ,  C07D413/12 ,  C07D401/12 ,  C07D413/04

Abstract: A compound for treating a protein kinase-related disease or disorder having a structure of formula (I) wherein L is NR8 or O; R1, R2, R3, R4, R5, R6 and R7 are defined herein. Compounds of formula (I) are useful for inhibition of protein kinases. Methods of using compounds of formula (I), stereoisomers, tautomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed

公开(公告)号：US20180186881A1

公开(公告)日：2018-07-05

申请号：US15859506

申请日：2017-12-30

Applicant: Development Center for Biotechnology

Inventor： Yu-Chen Yang ,  Li-Yu CHEN ,  Chia-Hua LI ,  Pei-Han TAI ,  Hong-Kai CHEN ,  Ying-Yung LOK ,  Chih-Yung HU ,  Chien-Tsun KUAN ,  Chung-Hsiun WU

IPC: C07K16/28 ,  A61P35/00 ,  G01N33/574

Abstract: An anti-human T-cell immunoglobulin domain and mucin domain 3 (TIM-3) antibody, can bind the peptides, comprising the amino-acid sequence RKGDVSL (SEQ ID NO: 9) and/or EKFNLKL (SEQ ID NO: 10) of human TIM-3 protein. The antibody can regulate immune cell activity. The antibody or binding fragment thereof is useful in diagnosis, prognosis, and treatment of cancers that have been reported to express cell-surface TIM-3 such as lung, liver, esophageal cancer and solid tumors.

公开(公告)号：US20180185312A1

公开(公告)日：2018-07-05

申请号：US15394856

申请日：2016-12-30

Applicant: Development Center for Biotechnology

Inventor： Jia-Ming Chang ,  I-Chun Ho

IPC: A61K31/198

CPC classification number: A61K31/198

Abstract: The present invention provides a composition for preventing or treating immune allergic airway disease, and uses of the composition in preparing drugs, wherein the composition comprises an effective amount of S-allyl-L-cysteine and a pharmaceutically acceptable carrier.

公开(公告)号：US09750804B2

公开(公告)日：2017-09-05

申请号：US14580127

申请日：2014-12-22

Applicant: Development Center for Biotechnology ,  National Health Research Institutes

Inventor： Shih-Chong Tsai ,  Mingl Chang ,  Ta-Tung Yuan ,  Shih-Chi Tseng ,  Shyi-Jou Chen ,  Wei-Tso Chia ,  Hsin-Yun Wang ,  Neng-Yao Shih ,  Ko-Jiunn Liu ,  Li-Tzong Chen

IPC: C07K16/28 ,  A61K39/39 ,  B63B15/02 ,  A61K39/395 ,  C07K16/40 ,  B63B1/12 ,  B63H9/08 ,  B63B15/00 ,  A61K39/00

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

Abstract: 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.

公开(公告)号：US09382331B2

公开(公告)日：2016-07-05

申请号：US14142186

申请日：2013-12-27

Applicant: Development Center for Biotechnology ,  National Health Research Institutes

Inventor： 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: A61K39/395 ,  C07K16/40 ,  G01N33/574 ,  A61K39/00

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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20160185876A1

公开(公告)日：2016-06-30

申请号：US14588212

申请日：2014-12-31

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

Inventor： 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: C07K16/40

CPC classification number: C07K16/40 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/732 ,  C07K2317/76 ,  C07K2317/92

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US09315491B2

公开(公告)日：2016-04-19

申请号：US14192301

申请日：2014-02-27

Applicant: DEVELOPMENT CENTER FOR BIOTECHNOLOGY ,  DCB-USA LLC

Inventor： Mann-Yan Kuo ,  Ying-Shuan Lee ,  Paonien Chen ,  Li Jung Chen ,  Yann Yu Lu ,  Yi-Ting Huang ,  Hung-Yi Hsu ,  Ping-Kuei Tsai

IPC: A61K31/5377 ,  C07D239/47 ,  A61K31/506 ,  C07D401/04 ,  C07D401/14 ,  C07D413/04 ,  A61K31/541 ,  A61K45/06 ,  C07D413/14 ,  C07D417/14 ,  C07D403/12 ,  C07D409/12 ,  C07D413/12

CPC classification number: A61K31/5377 ,  A61K31/541 ,  A61K45/06 ,  C07D239/47 ,  C07D401/04 ,  C07D401/14 ,  C07D403/12 ,  C07D409/12 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  A61K2300/00

Abstract: The present invention relates to pyrimidine compounds of formula (I): which are useful in treating mTOR kinase- or PI3K kinase-related diseases.

Abstract translation: 本发明涉及式（I）的嘧啶化合物：其可用于治疗mTOR激酶或PI3K激酶相关疾病。

公开(公告)号：US20160068595A1

公开(公告)日：2016-03-10

申请号：US14785139

申请日：2014-04-18

Applicant: Development Center for Biotechnology ,  DCB-USA LLC

Inventor： Chia-Cheng Wu ,  Chao-Yang Huang ,  Yu-Ying Lin ,  Yu-Jung Chen ,  Jiann-Shiun Lai

IPC: C07K16/24

CPC classification number: C07K16/244 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/76 ,  C07K2317/92

Abstract: A humanized antibody, or a scFv, Fab, or F(ab′)2 thereof, includes: a heavy chain variable region, or a homologous variant thereof, wherein the heavy chain variable region includes: heavy chain framework regions, CDRH1 that has the sequence of SEQ ID NO:19, CDRH2 that has the sequence of SEQ ID NO:20, and CDRH3 that has the sequence of SEQ ID NO:21, wherein the heavy chain variable region and the homologous variant share at least 90% sequence identity in the heavy chain framework regions; and a light chain variable region, or a homologous variant thereof, that includes: light chain framework regions, CDRL1 that has the sequence of SEQ ID NO:22, CDRL2 that has the sequences of SEQ ID NO:23, and CDRL3 that has the sequences of SEQ ID NO:24, wherein the light chain variable region and the homologous variant share at least 90% sequence identity in the light chain framework regions.

Abstract translation: 人源化抗体或其scFv，Fab或F（ab'）2包括：重链可变区或其同源变体，其中重链可变区包括：重链框架区，CDRH1具有 SEQ ID NO：19的序列，具有SEQ ID NO：20的序列的CDRH2和具有SEQ ID NO：21的序列的CDRH3，其中所述重链可变区和所述同源变体具有至少90％的序列同一性 在重链框架地区; 和轻链可变区或其同源变体，其包括：轻链框架区，具有SEQ ID NO：22的序列的CDRL1，具有SEQ ID NO：23的序列的CDRL2和具有SEQ ID NO：23的CDRL3，其具有 SEQ ID NO：24的序列，其中轻链可变区和同源变体在轻链框架区中共享至少90％的序列同一性。

公开(公告)号：US20140363372A1

公开(公告)日：2014-12-11

申请号：US14223800

申请日：2014-03-24

Applicant: DEVELOPMENT CENTER FOR BIOTECHNOLOGY ,  CHANG GUNG MEMORIAL HOSPITAL ,  ACADEMIA SINICA

Inventor： Alice L. Yu ,  John Yu ,  Ya-Hui Wang ,  Chuan-Lung Hsu ,  Yi-Chang Chen ,  Ying-Yung Lok

IPC: C07K16/30 ,  G01N33/574 ,  C12Q1/68 ,  A61K51/10

CPC classification number: C07K16/3015 ,  A61K39/39558 ,  C07K16/30 ,  C07K2317/55 ,  C07K2317/622 ,  C07K2317/732 ,  C07K2317/734 ,  C07K2317/92 ,  C12Q1/6886 ,  C12Q2600/158 ,  G01N33/57496

Abstract: A method for treating cancer includes administering to a subject in need thereof an antibody against a transmembrane and coiled-coil domains protein 3 (TMCC3), wherein the antibody binds to an epitope in an extracellular domain of TMCC3. The antibody binds to an epitope in an intercoil domain of TMCC3. A method of diagnosing or assessing a cancer condition includes assessing a level of expression or activity of a transmembrane and coiled-coil domains protein 3 (TMCC3) in a sample, wherein an increase in the level of expression of activity of TMCC3 as compared to a standard indicates the presence of cancer stem cells in the sample.

Abstract translation: 治疗癌症的方法包括向有需要的受试者施用针对跨膜和卷曲螺旋结构域蛋白3（TMCC3）的抗体，其中所述抗体结合TMCC3的细胞外结构域中的表位。 抗体结合TMCC3的线粒体结构域中的表位。 一种诊断或评估癌症病症的方法包括评估样品中跨膜和卷曲螺旋结构域蛋白3（TMCC3）的表达或活性水平，其中TMCC3的活性表达水平与 标准表明样品中存在癌干细胞。