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    Protease-resistant forms of VEGF-D, method of making and method of use
    1.
    发明申请
    Protease-resistant forms of VEGF-D, method of making and method of use 审中-公开
    蛋白酶抗性形式的VEGF-D，制备方法和使用方法

    公开(公告)号：US20070212390A1

    公开(公告)日：2007-09-13

    申请号：US11517290

    申请日：2006-09-08

    Applicant: Karri Paavonen ,  Steven Stacker ,  Marc Achen

    Inventor： Karri Paavonen ,  Steven Stacker ,  Marc Achen

    IPC: A61K38/18 ,  C07K14/475 ,  C07H21/04 ,  C12P21/06

    CPC classification number: C07K14/52

    Abstract: The present invention provides modified VEGF-D polypeptide variants that are resistant to serine protease processing and methods of making and using the same, as well pharmaceutical compositions comprising the peptide or a polynucleotide encoding the same. The VEGF-D variants comprise a VEGF homology domain, and at least one of (1) a C-terminal propeptide that is not cleavable by a serine protease, and (2) an N-terminal propeptide that is not cleavable by a serine protease. The VEGF-D variants can be made using site-directed mutagenesis. The VEGF-D variants are useful for the treatment of diseases such as cardiovascular disease and primary and secondary lymphedema, and for the prevention of stenosis and restenosis of blood vessels.

    Abstract translation: 本发明提供了对丝氨酸蛋白酶加工具有抗性的修饰的VEGF-D多肽变体及其制备和使用方法，以及包含该肽或编码该肽的多核苷酸的药物组合物。 VEGF-D变体包含VEGF同源结构域，和（1）不能被丝氨酸蛋白酶切割的C-末端前肽中的至少一种，和（2）不能被丝氨酸蛋白酶切割的N-末端前肽 。 VEGF-D变体可以使用定点突变来制备。 VEGF-D变体可用于治疗诸如心血管疾病和原发性和继发性淋巴水肿的疾病，以及用于预防血管狭窄和再狭窄。

    Methods for treating neoplastic disease characterized by vascular endothelial growth factor D expression, for screening for neoplastic disease or metastatic risk, and for maintaining vascularization of tissue
    2.
    发明申请
    Methods for treating neoplastic disease characterized by vascular endothelial growth factor D expression, for screening for neoplastic disease or metastatic risk, and for maintaining vascularization of tissue 有权
    用于治疗以血管内皮生长因子D表达为特征的肿瘤性疾病的方法，用于筛选肿瘤性疾病或转移性风险，以及维持组织血管化

    公开(公告)号：US20050202015A1

    公开(公告)日：2005-09-15

    申请号：US10627631

    申请日：2003-07-28

    Applicant: Marc Achen ,  Steven Stacker

    Inventor： Marc Achen ,  Steven Stacker

    IPC: A61K38/19 ,  C07K16/22 ,  C07K16/24 ,  G01N33/574 ,  A61K39/395

    CPC classification number: A61K38/1866 ,  A61K2039/505 ,  C07K16/22 ,  C07K16/24 ,  G01N33/57484 ,  G01N2333/475 ,  G01N2333/52

    Abstract: A method for treating and alleviating disease characterized by the expression of VEGF-D involving screening to find an organism with tumor cells expressing VEGF-D and administering an effective amount of a VEGF-D antagonist; a method for screening for neoplastic diseas, where detection of VEGF-D on or in a sample such as tumor cells, blood vessel endothelial cells or lymph vessel endothelial cells indicates neoplastic disease; a method for promoting and maintaining vascularization of normal tissue in an organism involving administering a vascularization promoting amount of VEGF-D or a fragment or analog thereof to the organism; a method for screening tumors for metastatic risk involving detecting expression of VEFG-D by a tumor which indicates metastatic risk; and a method of detecting micro-metastasis of neoplastic disease involving detection of VEGF-D on or in a tissue sample which indicates metastasis of a neoplastic disease.

    Abstract translation: 一种治疗和减轻疾病的方法，其特征在于VEGF-D的表达，其涉及筛选以发现具有表达VEGF-D的肿瘤细胞的生物体并施用有效量的VEGF-D拮抗剂; 用于筛选肿瘤性疾病的方法，其中检测肿瘤细胞，血管内皮细胞或淋巴管内皮细胞等样品上或样品中的VEGF-D表示肿瘤性疾病; 一种用于促进和维持生物体中正常组织的血管化的方法，包括向生物体施用血管促进量的VEGF-D或其片段或类似物; 用于筛选肿瘤转移性风险的方法，涉及通过指示转移性风险的肿瘤检测VEFG-D的表达; 以及检测涉及在指示肿瘤性疾病转移的组织样品中或其中检测VEGF-D的肿瘤性疾病的微转移的方法。

    METHODS AND COMPOSITIONS FOR ACTIVATING OR INHIBITING VEGF-D AND VEGF-C
    3.
    发明申请
    METHODS AND COMPOSITIONS FOR ACTIVATING OR INHIBITING VEGF-D AND VEGF-C 失效
    用于激活或抑制VEGF-D和VEGF-C的方法和组合物

    公开(公告)号：US20090169551A1

    公开(公告)日：2009-07-02

    申请号：US12331104

    申请日：2008-12-09

    Applicant: Bradley McColl ,  Megan E. Baldwin ,  Steven Stacker ,  Marc Achen

    Inventor： Bradley McColl ,  Megan E. Baldwin ,  Steven Stacker ,  Marc Achen

    IPC: A61K39/395 ,  A61P19/00 ,  A61P21/00

    CPC classification number: A61K38/484 ,  A61K2039/505 ,  C07K16/22 ,  C12Q1/37 ,  G01N2333/475 ,  G01N2333/71 ,  G01N2333/96433 ,  G01N2500/02 ,  G01N2500/04

    Abstract: Methods for Activating endothelial growth factors VEGF-C or VEGF-D with plasmin, and methods of treatment comprising administering a pharmaceutical compositions comprising plasmin. Also disclosed are methods of screening for inhibitors of activation of the growth factors by plasmin, and method of treatment by blocking activation of VEGF-C/D activation by plasmin. Further disclosed are methods for screening for other proteases that activate VEGF-CD, and for inhibitors of such activation. The invention further includes inhibitors of plasmin activity and methods of treating patients in need thereof with said inhibitors.

    Abstract translation: 用纤溶酶激活内皮生长因子VEGF-C或VEGF-D的方法和治疗方法包括施用包含纤溶酶的药物组合物。 还公开了通过纤溶酶筛选生长因子活化抑制剂的方法和通过阻断纤溶酶的VEGF-C / D活化激活的方法。 进一步披露的是筛选其它激活VEGF-CD的蛋白酶的方法以及用于这种激活抑制剂的方法。 本发明还包括纤溶酶活性抑制剂和用所述抑制剂治疗有需要的患者的方法。

    Vascular endothelial growth factor D (VEGF-D) antibodies and vectors, and methods of use
    4.
    发明申请
    Vascular endothelial growth factor D (VEGF-D) antibodies and vectors, and methods of use 审中-公开
    血管内皮生长因子D（VEGF-D）抗体和载体及其使用方法

    公开(公告)号：US20060177428A1

    公开(公告)日：2006-08-10

    申请号：US11304585

    申请日：2005-12-16

    Applicant: Marc Achen ,  Andrew Wilks ,  Steven Stacker ,  Kari Alitalo

    Inventor： Marc Achen ,  Andrew Wilks ,  Steven Stacker ,  Kari Alitalo

    IPC: A61K48/00 ,  C12N5/08

    CPC classification number: C07K14/475 ,  A61K38/00 ,  C07K14/52

    Abstract: Isolated nucleic acid molecule comprising an antisense nucleic acid sequence which is antisense to a polynucleotide that encodes a VEGF-D polypeptide, vectors and host cells including the same. Also disclosed are methods of inhibiting VEGF-D function or expression in a mammal, for example, in treating cancer, comprising administering to the mammal in need thereof a vector of the present invention.

    Abstract translation: 分离的核酸分子包含与编码VEGF-D多肽的多核苷酸反义的反义核酸序列，载体和包含其的宿主细胞。 还公开了抑制哺乳动物的VEGF-D功能或表达的方法，例如用于治疗癌症，包括向有需要的哺乳动物施用本发明的载体。

    Method for activating only the vascular endothelial growth factor receptor-3 and uses thereof
    5.
    发明授权
    Method for activating only the vascular endothelial growth factor receptor-3 and uses thereof 失效
    仅激活血管内皮生长因子受体-3的方法及其用途

    公开(公告)号：US06689352B2

    公开(公告)日：2004-02-10

    申请号：US09847524

    申请日：2001-05-03

    Applicant: Marc Achen ,  Steven Stacker

    Inventor： Marc Achen ,  Steven Stacker

    IPC: A61K3819

    CPC classification number: A61K38/1866 ,  C07K14/52

    Abstract: A method for activating only the vascular endothelial growth factor receptor-3 has been created. The method comprises administration of a composition comprising a polypeptide to an animal wherein the composition has the ability to stimulate one or more lymphatic vessel endothelial cells to proliferate, differentiate, migrate, or survive. Methods are also provided to selectively activate a VEGF receptor-3, to screen for neoplastic disease characterized by an increase in lymph vessel endothelial cells, and to identify lymph vessel endothelial cells.

    Abstract translation: 已经创建了仅激活血管内皮生长因子受体-3的方法。 该方法包括向动物施用包含多肽的组合物，其中组合物具有刺激一个或多个淋巴管内皮细胞增殖，分化，迁移或存活的能力。 还提供了选择性激活VEGF受体-3以筛选以淋巴管内皮细胞增多为特征的肿瘤性疾病以及鉴定淋巴管内皮细胞的方法。

    Vascular Endothelial Growth Factor D(VEGF-D) Antibodies and Vectors, and Methods of Uses
    7.
    发明申请
    Vascular Endothelial Growth Factor D(VEGF-D) Antibodies and Vectors, and Methods of Uses 有权
    血管内皮生长因子D（VEGF-D）抗体和载体及其使用方法

    公开(公告)号：US20070298493A1

    公开(公告)日：2007-12-27

    申请号：US11843867

    申请日：2007-08-23

    Applicant: Marc Achen ,  Andrew Wilks ,  Steven Stacker ,  Kari Alitalo

    Inventor： Marc Achen ,  Andrew Wilks ,  Steven Stacker ,  Kari Alitalo

    IPC: C12N5/10 ,  C12N15/63

    CPC classification number: C07K14/475 ,  A61K38/00 ,  C07K14/52

    Abstract: VEGF-D, a new member of the PDGF family of growth factors, which among other things stimulates endothelial cell proliferation and angiogenesis and increases vascular permeability, as well as nucleotide sequences encoding it, methods for producing it, antibodies and other antagonists to it, transfected or transformed host cells for expressing it, pharmaceutical compositions containing it, and uses thereof in medical and diagnostic applications.

    Abstract translation: VEGF-D是生长因子PDGF家族的新成员，其中刺激内皮细胞增殖和血管生成并增加血管通透性，以及编码其的核苷酸序列，其生产方法，抗体及其它拮抗剂， 转染或转化的宿主细胞进行表达，含有它的药物组合物及其在医学和诊断应用中的用途。

    Methods and compositions for activating VEGF-D and VEGF-C
    9.
    发明授权
    Methods and compositions for activating VEGF-D and VEGF-C 失效
    激活VEGF-D和VEGF-C的方法和组合物

    公开(公告)号：US07479270B2

    公开(公告)日：2009-01-20

    申请号：US10522232

    申请日：2003-07-21

    Applicant: Bradley McColl ,  Megan E. Baldwin ,  Steven Stacker ,  Marc Achen

    Inventor： Bradley McColl ,  Megan E. Baldwin ,  Steven Stacker ,  Marc Achen

    IPC: A61K38/43 ,  A61K38/48 ,  C07K14/435

    CPC classification number: A61K38/484 ,  A61K2039/505 ,  C07K16/22 ,  C12Q1/37 ,  G01N2333/475 ,  G01N2333/71 ,  G01N2333/96433 ,  G01N2500/02 ,  G01N2500/04

    Abstract: Methods for activating endothelial growth factors VEGF-C or VEGF-D with plasmin, and methods of treatment comprising administering a phamarceutical compositions comprising plasmin. Also disclosed are methods for screening for inhibitors of activation of the growth factors by plasmin, and method of treatment by blocking activation of VEGF-C/D activation by plasmin. Further disclosed are methods for screening for other proteases that activate VEGF-C/D, and for inhibitors of such activation. The invention further includes inhibitors of plasmin activity and methods of treating patients in need thereof with said inhibitors.

    Abstract translation: 用纤溶酶激活内皮生长因子VEGF-C或VEGF-D的方法和治疗方法包括施用包含纤溶酶的络合物组合物。 还公开了用于筛选纤溶酶激活生长因子抑制剂的方法，以及通过阻断纤溶酶的VEGF-C / D活化激活的方法。 进一步公开的是筛选其它激活VEGF-C / D的蛋白酶的方法，以及用于这种活化抑制剂的方法。 本发明还包括纤溶酶活性抑制剂和用所述抑制剂治疗有需要的患者的方法。

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