公开(公告)号：US20060099708A1

公开(公告)日：2006-05-11

申请号：US11303935

申请日：2005-12-19

Applicant: Thomas Ciossek ,  Axel Ullrich ,  Birgit Millauer

Inventor： Thomas Ciossek ,  Axel Ullrich ,  Birgit Millauer

IPC: C12N5/06 ,  C07K16/40

CPC classification number: C07K16/40 ,  A61K38/00 ,  C07K14/71

Abstract: The present invention relates to MDK1 polypeptides, nucleic acids encoding such polypeptides, cells, tissues and animals containing such nucleic acids, antibodies to such polypeptides, assays utilizing such polypeptides, and methods relating to all of the foregoing. Methods for treatment, diagnosis, and screening are provided for diseases or conditions characterized by an abnormality in a signal transduction disorder. The signal transduction pathway involves an interaction between a MDK1 receptor tyrosine kinase and a receptor for the kinase. The MDK1 receptor tyrosine kinase may be truncated and lack a kinase domain and may be selected from the group consisting of MDK1.T1, MDK1.T2, MDK1.Δ1 and MDK1.Δ2.

Abstract translation: 本发明涉及MDK1多肽，编码这种多肽的核酸，含有此类核酸的细胞，组织和动物，对这些多肽的抗体，利用这些多肽的测定法，以及与上述所有相关的方法。 提供治疗，诊断和筛查的方法用于以信号转导障碍异常为特征的疾病或病症。 信号转导途径涉及MDK1受体酪氨酸激酶与激酶受体之间的相互作用。 MDK1受体酪氨酸激酶可能被截短并缺少激酶结构域，并且可以选自MDK1.T1，MDK1T2，MDK1Delta1和MDK1Delta2。

公开(公告)号：US06177401B1

公开(公告)日：2001-01-23

申请号：US08193829

申请日：1994-02-09

Applicant: Axel Ullrich ,  Werner Risau ,  Birgit Millauer

Inventor： Axel Ullrich ,  Werner Risau ,  Birgit Millauer

IPC: A61K3100

CPC classification number: C07D487/04 ,  A61K31/235 ,  A61K31/275 ,  A61K31/277 ,  A61K31/38 ,  A61K31/40 ,  A61K31/415 ,  A61K31/42 ,  A61K31/495 ,  A61K31/502 ,  A61K31/505 ,  A61K31/517 ,  A61K31/535 ,  A61K38/00 ,  C07C229/60 ,  C07C255/36 ,  C07C255/40 ,  C07C255/41 ,  C07C255/66 ,  C07C317/46 ,  C07C327/44 ,  C07D209/18 ,  C07D239/93 ,  C07D239/94 ,  C07D241/42 ,  C07D241/44 ,  C07K14/71 ,  C07K16/2863 ,  C07K2319/32 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/502 ,  G01N33/5064 ,  G01N33/5091 ,  G01N33/6893 ,  G01N2333/71 ,  G01N2500/04

Abstract: The present invention relates to the use of proteins, peptides and organic molecules capable of modulating Flk-1 receptor signal transduction in order to inhibit or promote angiogenesis and vasculogenesis. The invention is based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.

Abstract translation: 本发明涉及能够调节Flk-1受体信号转导以抑制或促进血管生成和血管发生的蛋白质，肽和有机分子的用途。 本发明部分基于Flk-1酪氨酸激酶受体表达与内皮细胞相关的证据，以及作为Flk-1的高亲和力配体的血管内皮生长因子（VEGF）的鉴定。 这些结果表明Flk-1在血管发生和血管发生过程中在信号系统中的主要作用。 描述了表达Flk-1的宿主细胞的工程和表达Flk-1的用途以通过激动剂或拮抗剂活性评价和筛选参与Flk-1调节的VEGF和类似物的用途。本发明还涉及使用 FLK-1配体，包括VEGF激动剂和拮抗剂，通过调节血管发生和血管生成来治疗病症，包括癌症。

公开(公告)号：US07964399B2

公开(公告)日：2011-06-21

申请号：US10799782

申请日：2004-03-15

Applicant: Axel Ullrich ,  Werner Risau ,  Birgit Millauer ,  Aviv Gazit ,  Alex Levitzki

Inventor： Axel Ullrich ,  Werner Risau ,  Birgit Millauer ,  Aviv Gazit ,  Alex Levitzki

IPC: C12N5/10 ,  C07K14/71

CPC classification number: G01N33/502 ,  A61K31/235 ,  A61K31/275 ,  A61K31/277 ,  A61K31/38 ,  A61K31/40 ,  A61K31/415 ,  A61K31/42 ,  A61K31/495 ,  A61K31/502 ,  A61K31/505 ,  A61K31/517 ,  A61K31/535 ,  A61K38/00 ,  C07C229/60 ,  C07C255/36 ,  C07C255/40 ,  C07C255/41 ,  C07C255/66 ,  C07C317/46 ,  C07C327/44 ,  C07D209/18 ,  C07D239/93 ,  C07D239/94 ,  C07D241/42 ,  C07D241/44 ,  C07D487/04 ,  C07K14/71 ,  C07K16/2863 ,  C07K2319/00 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/5041 ,  G01N33/5064 ,  G01N33/6893 ,  G01N2333/71 ,  G01N2500/04

Abstract: The present invention relates to the use of ligands for the FLK-1 receptor for the modulation of angiogenesis and vasculogenesis. The invention s based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.

Abstract translation: 本发明涉及用于FLK-1受体的配体用于调节血管发生和血管发生的用途。 本发明部分地基于Flk-1酪氨酸激酶受体表达与内皮细胞相关的证据，以及作为Flk-1的高亲和力配体的血管内皮生长因子（VEGF）的鉴定。 这些结果表明Flk-1在血管发生和血管发生过程中在信号系统中的主要作用。 描述表达Flk-1的宿主细胞的工程和表达Flk-1的用途以通过激动剂或拮抗剂活性评价和筛选参与Flk-1调节的VEGF的类似物。 本发明还涉及FLK-1配体，包括VEGF激动剂和拮抗剂在治疗疾病，包括癌症中的用途，通过调节血管生成和血管生成。

公开(公告)号：US20050107321A1

公开(公告)日：2005-05-19

申请号：US10799782

申请日：2004-03-15

Applicant: Axel Ullrich ,  Werner Risau ,  Birgit Millauer ,  Aviv Gazit ,  Alex Levitzki

Inventor： Axel Ullrich ,  Werner Risau ,  Birgit Millauer ,  Aviv Gazit ,  Alex Levitzki

IPC: A61K31/235 ,  A61K31/275 ,  A61K31/277 ,  A61K31/38 ,  A61K31/40 ,  A61K31/415 ,  A61K31/42 ,  A61K31/495 ,  A61K31/502 ,  A61K31/505 ,  A61K31/517 ,  A61K31/535 ,  A61K38/00 ,  C07C229/60 ,  C07C255/36 ,  C07C255/40 ,  C07C255/41 ,  C07C255/66 ,  C07C317/46 ,  C07C327/44 ,  C07D209/18 ,  C07D239/93 ,  C07D239/94 ,  C07D241/42 ,  C07D241/44 ,  C07D487/04 ,  C07D498/04 ,  C07K14/71 ,  C07K16/28 ,  G01N33/50 ,  G01N33/68 ,  A61K48/00 ,  C07H21/04 ,  C07K14/705 ,  C12N15/867

CPC classification number: G01N33/502 ,  A61K31/235 ,  A61K31/275 ,  A61K31/277 ,  A61K31/38 ,  A61K31/40 ,  A61K31/415 ,  A61K31/42 ,  A61K31/495 ,  A61K31/502 ,  A61K31/505 ,  A61K31/517 ,  A61K31/535 ,  A61K38/00 ,  C07C229/60 ,  C07C255/36 ,  C07C255/40 ,  C07C255/41 ,  C07C255/66 ,  C07C317/46 ,  C07C327/44 ,  C07D209/18 ,  C07D239/93 ,  C07D239/94 ,  C07D241/42 ,  C07D241/44 ,  C07D487/04 ,  C07K14/71 ,  C07K16/2863 ,  C07K2319/00 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/5041 ,  G01N33/5064 ,  G01N33/6893 ,  G01N2333/71 ,  G01N2500/04

Abstract: The present invention relates to the use of ligands for the FLK-1 receptor for the modulation of angiogenesis and vasculogenesis. The invention is based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.

Abstract translation: 本发明涉及用于FLK-1受体的配体用于调节血管发生和血管发生的用途。 本发明部分基于Flk-1酪氨酸激酶受体表达与内皮细胞相关的证据，以及作为Flk-1的高亲和力配体的血管内皮生长因子（VEGF）的鉴定。 这些结果表明Flk-1在血管发生和血管发生过程中在信号系统中的主要作用。 描述表达Flk-1的宿主细胞的工程和表达Flk-1的用途以通过激动剂或拮抗剂活性评价和筛选参与Flk-1调节的VEGF的类似物。 本发明还涉及FLK-1配体，包括VEGF激动剂和拮抗剂在治疗疾病，包括癌症中的用途，通过调节血管生成和血管生成。

公开(公告)号：US06361984B1

公开(公告)日：2002-03-26

申请号：US08438265

申请日：1995-05-09

Applicant: Thomas Ciossek ,  Axel Ullrich ,  Birgit Millauer

Inventor： Thomas Ciossek ,  Axel Ullrich ,  Birgit Millauer

IPC: C12N900

CPC classification number: C07K16/40 ,  A61K38/00 ,  C07K14/71

Abstract: The present invention relates to MDK1 polypeptides, nucleic acids encoding such polypeptides, cells, tissues and animals containing such nucleic acids, antibodies to such polypeptides, assays utilizing such polypeptides, and methods relating to all of the foregoing. Methods for treatment, diagnosis, and screening are provided for diseases or conditions characterized by an abnormality in a signal transduction disorder. The signal transduction pathway involves an interaction between a MDK1 receptor tyrosine kinase and a receptor for the kinase. The MDK1 receptor tyrosine kinase may be truncated and lack a kinase domain and may be selected from the group consisting of MDK1.T1, MDK1.T2, MDK1.&Dgr;1 and MDK1.&Dgr;2.

Abstract translation: 本发明涉及MDK1多肽，编码这种多肽的核酸，含有这种核酸的细胞，组织和动物，这种多肽的抗体，利用这些多肽的测定法，以及与上述所有方法有关的方法。治疗，诊断和 为特征为信号转导障碍异常的疾病或病症提供筛查。 信号转导途径涉及MDK1受体酪氨酸激酶与激酶受体之间的相互作用。 MDK1受体酪氨酸激酶可能被截短并缺少激酶结构域，并且可以选自MDK1.T1，MDK1.T2，MDK1.DELTA1和MDK1.DELTA2。

公开(公告)号：US5851999A

公开(公告)日：1998-12-22

申请号：US443861

申请日：1995-05-22

Applicant: Axel Ullrich ,  Werner Risau ,  Birgit Millauer ,  Aviv Gazit ,  Alex Levitzki

Inventor： Axel Ullrich ,  Werner Risau ,  Birgit Millauer ,  Aviv Gazit ,  Alex Levitzki

IPC: G01N33/53 ,  A61K31/047 ,  A61K31/235 ,  A61K31/245 ,  A61K31/275 ,  A61K31/277 ,  A61K31/38 ,  A61K31/381 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/415 ,  A61K31/42 ,  A61K31/495 ,  A61K31/496 ,  A61K31/502 ,  A61K31/505 ,  A61K31/517 ,  A61K31/535 ,  A61K38/00 ,  A61K39/395 ,  A61P1/00 ,  A61P3/08 ,  A61P3/10 ,  A61P9/00 ,  A61P11/00 ,  A61P13/02 ,  A61P15/00 ,  A61P17/00 ,  A61P27/02 ,  A61P35/00 ,  C07C229/60 ,  C07C255/34 ,  C07C255/36 ,  C07C255/40 ,  C07C255/41 ,  C07C255/66 ,  C07C317/44 ,  C07C317/46 ,  C07C327/44 ,  C07D209/18 ,  C07D209/20 ,  C07D231/38 ,  C07D239/93 ,  C07D239/94 ,  C07D241/42 ,  C07D241/44 ,  C07D261/08 ,  C07D333/42 ,  C07D403/06 ,  C07D487/04 ,  C07D491/052 ,  C07D498/04 ,  C07H21/04 ,  C07K14/71 ,  C07K16/28 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12P21/02 ,  C12P21/08 ,  C12R1/91 ,  G01N33/50 ,  G01N33/566 ,  G01N33/577 ,  G01N33/68 ,  A61K48/00 ,  C12N5/00 ,  C12N15/00

CPC classification number: C07D487/04 ,  A61K31/235 ,  A61K31/275 ,  A61K31/277 ,  A61K31/38 ,  A61K31/40 ,  A61K31/415 ,  A61K31/42 ,  A61K31/495 ,  A61K31/502 ,  A61K31/505 ,  A61K31/517 ,  A61K31/535 ,  C07C229/60 ,  C07C255/36 ,  C07C255/40 ,  C07C255/41 ,  C07C255/66 ,  C07C317/46 ,  C07C327/44 ,  C07D209/18 ,  C07D239/93 ,  C07D239/94 ,  C07D241/42 ,  C07D241/44 ,  C07K14/71 ,  C07K16/2863 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/502 ,  G01N33/5064 ,  G01N33/5091 ,  G01N33/6893 ,  A61K38/00 ,  C07K2319/32 ,  G01N2333/71 ,  G01N2500/04

Abstract: The present invention relates to the use of ligands for the FLK-1 receptor for the modulation of angiogenesis and vasculogenesis. The invention is based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.

Abstract translation: 本发明涉及用于FLK-1受体的配体用于调节血管发生和血管发生的用途。 本发明部分基于Flk-1酪氨酸激酶受体表达与内皮细胞相关的证据，以及作为Flk-1的高亲和力配体的血管内皮生长因子（VEGF）的鉴定。 这些结果表明Flk-1在血管发生和血管发生过程中在信号系统中的主要作用。 描述表达Flk-1的宿主细胞的工程和表达Flk-1的用途以通过激动剂或拮抗剂活性评价和筛选参与Flk-1调节的VEGF的类似物。 本发明还涉及FLK-1配体，包括VEGF激动剂和拮抗剂在治疗疾病，包括癌症中的用途，通过调节血管生成和血管生成。

公开(公告)号：US07034112B2

公开(公告)日：2006-04-25

申请号：US10073064

申请日：2002-02-12

Applicant: Thomas Ciossek ,  Axel Ullrich ,  Birgit Millauer

Inventor： Thomas Ciossek ,  Axel Ullrich ,  Birgit Millauer

IPC: C07K17/00

CPC classification number: C07K16/40 ,  A61K38/00 ,  C07K14/71

Abstract: The present invention relates to MDK1 polypeptides, nucleic acids encoding such polypeptides, cells, tissues and animals containing such nucleic acids, antibodies to such polypeptides, assays utilizing such polypeptides, and methods relating to all of the foregoing.Methods for treatment, diagnosis, and screening are provided for diseases or conditions characterized by an abnormality in a signal transduction disorder. The signal transduction pathway involves an interaction between a MDK1 receptor tyrosine kinase and a receptor for the kinase. The MDK1 receptor tyrosine kinase may be truncated and lack a kinase domain and may be selected from the group consisting of MDK1.T1, MDK1.T2, MDK1.Δ1 and MDK1.Δ2.

公开(公告)号：US06872699B2

公开(公告)日：2005-03-29

申请号：US09766678

申请日：2001-01-23

Applicant: Axel Ullrich ,  Werner Risau ,  Birgit Millauer ,  Aviv Gazit ,  Alex Levitzki

Inventor： Axel Ullrich ,  Werner Risau ,  Birgit Millauer ,  Aviv Gazit ,  Alex Levitzki

IPC: A61K31/235 ,  A61K31/275 ,  A61K31/277 ,  A61K31/38 ,  A61K31/40 ,  A61K31/415 ,  A61K31/42 ,  A61K31/495 ,  A61K31/502 ,  A61K31/505 ,  A61K31/517 ,  A61K31/535 ,  A61K38/00 ,  C07C229/60 ,  C07C255/36 ,  C07C255/40 ,  C07C255/41 ,  C07C255/66 ,  C07C317/46 ,  C07C327/44 ,  C07D209/18 ,  C07D239/93 ,  C07D239/94 ,  C07D241/42 ,  C07D241/44 ,  C07D487/04 ,  C07D498/04 ,  C07K14/71 ,  C07K16/28 ,  G01N33/50 ,  G01N33/68

CPC classification number: G01N33/502 ,  A61K31/235 ,  A61K31/275 ,  A61K31/277 ,  A61K31/38 ,  A61K31/40 ,  A61K31/415 ,  A61K31/42 ,  A61K31/495 ,  A61K31/502 ,  A61K31/505 ,  A61K31/517 ,  A61K31/535 ,  A61K38/00 ,  C07C229/60 ,  C07C255/36 ,  C07C255/40 ,  C07C255/41 ,  C07C255/66 ,  C07C317/46 ,  C07C327/44 ,  C07D209/18 ,  C07D239/93 ,  C07D239/94 ,  C07D241/42 ,  C07D241/44 ,  C07D487/04 ,  C07K14/71 ,  C07K16/2863 ,  C07K2319/00 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/5041 ,  G01N33/5064 ,  G01N33/6893 ,  G01N2333/71 ,  G01N2500/04

Abstract: The present invention relates to the use of ligands for the FLK-1 receptor for the modulation of angiogenesis and vasculogenesis. The invention is based, in part, on the demonstration that Flk-1 tyrosine kinase receptor expression is associated with endothelial cells and the identification of vascular endothelial growth factor (VEGF) as the high affinity ligand of Flk-1. These results indicate a major role for Flk-1 in the signaling system during vasculogenesis and angiogenesis. Engineering of host cells that express Flk-1 and truncated Flk-1 and the uses of expressed Flk-1 to evaluate and screen for drugs and analogs of VEGF involved in Flk-1 modulation by either agonist or antagonist activities is described. The invention also relates to the use of FLK-1 ligands, including VEGF agonists and antagonists, in the treatment of disorders, including cancer, by modulating vasculogenesis and angiogenesis.

Abstract translation: 本发明涉及用于FLK-1受体的配体用于调节血管发生和血管发生的用途。 本发明部分基于Flk-1酪氨酸激酶受体表达与内皮细胞相关的证据，以及作为Flk-1的高亲和力配体的血管内皮生长因子（VEGF）的鉴定。 这些结果表明Flk-1在血管发生和血管发生过程中在信号系统中的主要作用。 描述了表达Flk-1和截短的Flk-1的宿主细胞的工程和表达的Flk-1用于通过激动剂或拮抗剂活性评价和筛选参与Flk-1调节的VEGF的类似物的用途。 本发明还涉及FLK-1配体，包括VEGF激动剂和拮抗剂在治疗疾病，包括癌症中的用途，通过调节血管生成和血管生成。

公开(公告)号：US06300482B1

公开(公告)日：2001-10-09

申请号：US08368776

申请日：1995-01-03

Applicant: Thomas Ciossek ,  Axel Ullrich ,  Birgit Millauer

Inventor： Thomas Ciossek ,  Axel Ullrich ,  Birgit Millauer

IPC: C07H2102

CPC classification number: C07K16/40 ,  A61K38/00 ,  C07K14/71

Abstract: The present invention relates to MDK1 polypeptides, nucleic acids encoding such polypeptides, cells, tissues and animals containing such nucleic acids, antibodies to such polypeptides, assays utilizing such polypeptides, and methods relating to all of the foregoing. Methods for treatment, diagnosis, and screening are provided for diseases or conditions characterized by an abnormality in a signal transduction disorder. The signal transduction pathway involves an interaction between a MDK1 receptor tyrosine kinase and a receptor for the kinase. The MDK1 receptor tyrosine kinase may be truncated and lack a kinase domain and may be selected from the group consisting of MDK1.T1, MDK1.T2, MDK1.&Dgr;1 and MDK1.&Dgr;2.

Abstract translation: 本发明涉及MDK1多肽，编码这种多肽的核酸，含有这种核酸的细胞，组织和动物，这种多肽的抗体，利用这些多肽的测定法，以及与上述所有方法有关的方法。治疗，诊断和 为特征为信号转导障碍异常的疾病或病症提供筛查。 信号转导途径涉及MDK1受体酪氨酸激酶与激酶受体之间的相互作用。 MDK1受体酪氨酸激酶可能被截短并缺少激酶结构域，并且可以选自MDK1.T1，MDK1.T2，MDK1.DELTA1和MDK1.DELTA2。