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。

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。

公开(公告)号：US07045133B2

公开(公告)日：2006-05-16

申请号：US09761636

申请日：2001-01-18

Applicant: Marc G. Achen ,  Richard A. Hughes ,  Steven Stacker ,  Angela Cendron

Inventor： Marc G. Achen ,  Richard A. Hughes ,  Steven Stacker ,  Angela Cendron

IPC: A61K38/12 ,  A61K38/04 ,  A61K39/00

CPC classification number: C07K14/52 ,  A61K38/00 ,  A61K39/00

Abstract: Monomeric monocyclic peptide inhibitors and dimeric bicyclic peptide inhibitors based on exposed loop fragments of a growth factor protein, such as loop 1, 2 or 3 of VEGF-D, and methods of making them are described as well as pharmaceutical compositions containing them and methods utilizing them.

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。

公开(公告)号：US07928061B2

公开(公告)日：2011-04-19

申请号：US11929120

申请日：2007-10-30

Applicant: Marc G. Achen ,  Steven Stacker ,  Kari Alitalo ,  Andrew F. Wilks

Inventor： Marc G. Achen ,  Steven Stacker ,  Kari Alitalo ,  Andrew F. Wilks

IPC: A61K38/18 ,  C07K14/475 ,  C07K14/49

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

Abstract: Disclosed herein are various uses for VEGF-D polypeptides. Exemplary uses include methods of stimulating endothelial cell proliferation, methods of stimulating vascular permeability, methods of stimulating angiogenesis and methods of activating VEGFR-2 and VEGFR-3 using VEGF-D polypeptides.

Abstract translation: 本文公开了VEGF-D多肽的各种用途。 示例性用途包括刺激内皮细胞增殖的方法，刺激血管通透性的方法，刺激血管发生的方法和使用VEGF-D多肽激活VEGFR-2和VEGFR-3的方法。

公开(公告)号：US07534572B2

公开(公告)日：2009-05-19

申请号：US10627631

申请日：2003-07-28

Applicant: Marc Achen ,  Steven Stacker

Inventor： Marc Achen ,  Steven Stacker

IPC: G01N33/53 ,  G01N33/559 ,  G01N33/561 ,  G01N33/574 ,  G01N33/577 ,  C12P21/08

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.

公开(公告)号：US20080058258A1

公开(公告)日：2008-03-06

申请号：US11772089

申请日：2007-06-29

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

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

IPC: A61K38/16 ,  A61P43/00 ,  C07K14/00 ,  C07K14/485 ,  C12N5/00

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。

公开(公告)号：US20070224194A1

公开(公告)日：2007-09-27

申请号：US11566195

申请日：2006-12-01

Applicant: Bradley McColl ,  Steven Stacker ,  Marc Achen ,  Karri Paavonen

Inventor： Bradley McColl ,  Steven Stacker ,  Marc Achen ,  Karri Paavonen

IPC: A61K31/7052 ,  A61K39/395

CPC classification number: C07K14/4703 ,  C07K5/1027 ,  C12N15/113

Abstract: Proprotein convertase inhibitor has been found to block proteolytic processing and activation of VEGF-C and VEGF-D and inhibit angiogenesis and/or lymphangiogenesis. Method and composition are disclosed for inhibiting angiogenesis and/or lymphangiogenesis, and for treating conditions associated with excessive angiogenesis, such as tumors and/or retinopathies, as well as conditions associated with lymphangiogenesis, such as the metastatic spread of malignancies, macular degeneration, inflammatory mediated diseases, rheumatoid arthritis, diabetic retinopathy and psoriasis in a patient. The inventive method and composition utilize proprotein convertase antagonist selected from the group consisting of an anti-proprotein convertase antibody, an antisense nucleic acid molecule against a polynucleotide coding for a proprotein convertase, and an siRNA for inhibiting proprotein convertase expression, as well as proprotein convertase inhibitors.

Abstract translation: 已经发现前蛋白转化酶抑制剂阻断VEGF-C和VEGF-D的蛋白水解加工和活化并抑制血管生成和/或淋巴管生成。 公开了用于抑制血管发生和/或淋巴管生成的方法和组合，以及用于治疗与过度血管发生相关的病症，例如肿瘤和/或视网膜病变，以及与淋巴管生成相关的病症，例如恶性肿瘤的转移性扩散，黄斑变性，炎性 介导的疾病，类风湿性关节炎，糖尿病性视网膜病变和银屑病。 本发明的方法和组合物使用选自抗前体蛋白转化酶抗体，针对编码前蛋白转化酶的多核苷酸的反义核酸分子和用于抑制前蛋白转化酶表达的siRNA以及前蛋白转化酶 抑制剂。

公开(公告)号：US07122654B2

公开(公告)日：2006-10-17

申请号：US10274953

申请日：2002-10-22

Applicant: Marc G. Achen ,  Andrew F. Wilks ,  Steven Stacker ,  Kari Alitalo

Inventor： Marc G. Achen ,  Andrew F. Wilks ,  Steven Stacker ,  Kari Alitalo

IPC: C12N15/12 ,  C12N15/18 ,  C07K14/475 ,  C07K14/49

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.

公开(公告)号：US20050282228A1

公开(公告)日：2005-12-22

申请号：US10522232

申请日：2003-07-21

Applicant: Bradley Mccoll ,  Megan Baldwin ,  Steven Stacker ,  Narc Achen

Inventor： Bradley Mccoll ,  Megan Baldwin ,  Steven Stacker ,  Narc Achen

IPC: A61K38/48 ,  C07K16/22 ,  C12Q1/37 ,  G01N33/53

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。