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1. 发明申请

WO2009014564A9 MODIFIED PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 MOLECULE AND METHODS BASED THEREON 审中-公开
公开(公告)号：WO2009014564A9
公开(公告)日：2009-01-29
申请号：PCT/US2008/005272
申请日：2008-04-24
申请人： THE UNIVERSITY OF TOLEDO , JANKUN, Jerzy , SKRZYPCZAK-JANKUN, Ewa , SELMAN, Steven, H.
发明人： JANKUN, Jerzy , SKRZYPCZAK-JANKUN, Ewa , SELMAN, Steven, H.
IPC分类号： A61K38/55
摘要： The present invention relates to a modified plasminogen activator inhibitor type- 1 (PAI-1) molecule that displays an increased in vivo half-life of the active form of PAI- 1, but is deficient in one or more functional activities as compared to the wild-type PAI- 1 protein. The modified PAI-1 molecule that displays an increased half-life further displays at least one of the following funtional characteristics: (i) decreased binding activity to at least one of the following molecules: urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and vitronectin (Vn); and (ii) decreased specific activity against at least one of the following molecules: uPA, tPA and Vn. The invention further relates to pharmaceutical compositions comprising modified PAI-I molecules and methods of using these pharmaceutical compositions for treatment.

2. 发明申请

WO2009045412A3 METHODS OF TREATMENT USING MODIFIED PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 MOLECULES 审中-公开
公开(公告)号：WO2009045412A3
公开(公告)日：2009-04-09
申请号：PCT/US2008/011330
申请日：2008-10-01
申请人： AMERICAN DIAGNOSTICA, INC. , THE UNIVERSITY OF TOLEDO , JANKUN, Jerzy , SKRZYPCZAK-JANKUN, Ewa , SELMAN, Steven, H. , GREENFIELD, Robert, S.
发明人： JANKUN, Jerzy , SKRZYPCZAK-JANKUN, Ewa , SELMAN, Steven, H. , GREENFIELD, Robert, S.
IPC分类号： A61K38/57 , A61K38/48 , A61P7/04
摘要： The present invention generally relates to methods of treating bleeding diseases and disorders and to promote wound healing. The methods comprises administering a procoagulant, preferably factor VII a, and a modified plasminogen activator inhibitor type-1 (PAI-1) molecule that displays an increased in vivo half-life of the active form of the PAI-1 molecule. The invention also relates to methods of treating respiratory diseases using a modified PAI-1 molecule.

3. 发明申请

WO2003080646A3 MODIFIED PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 AND METHODS BASED THEREON 审中-公开
公开(公告)号：WO2003080646A3
公开(公告)日：2003-10-02
申请号：PCT/US2003/006679
申请日：2003-03-04
申请人： MEDICAL COLLEGE OF OHIO , THE UNIVERSITY OF TOLEDO , SWIERCZ, Rafal , SELMAN, Steven, H. , JANKUN, Jerzy , SKRZYPCZAK-JANKUN, Ewa , CHOROSTOWSKA-WYNIMKO, Joanna
发明人： SWIERCZ, Rafal , SELMAN, Steven, H. , JANKUN, Jerzy , SKRZYPCZAK-JANKUN, Ewa , CHOROSTOWSKA-WYNIMKO, Joanna
IPC分类号： C07K14/00
摘要： The present invention is based upon the discovery that modified plasminogen activator inhibitor type-I (PAI-1) in which two or more amino acid residues that do not contain a sulfliydryl group have been replaced with amino acid residues that contain a sulfhydryl group and, therefore, forms intramolecular disulfide bonds, have increased in vivo half-life. Also disclosed are the modified PAI-1 proteins, derivatives and analogs thereof, specific antibodies, nucleic acid molecules and host cells. Methods for producing modified PAI-1, derivatives and analogs are also provided. The invention further relates to Therapeutics, pharmaceutical compositions and method of using the composition for treatment. The invention may be used to inhibit angiogenesis in a subject, thereby treating diseases or conditions associated with undesired angiogenesis and cell proliferation. Such conditions include psoriasis, chronic inflammation, tumor invasion and metastasis and conditions in which angiogenesis is pathogenic. The modified PAI-1 molecules of the present invention are useful for the treatment, prophylaxis, management and amelioration of cardiovascular diseases such as, but not limited to those that are related to hyerfibrinolysis, hemophilia, and vessel leakage syndrome.

4. 发明公开

EP1487867A2 MODIFIED PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 AND METHODS BASED THEREON 有权
标题翻译：改性型纤溶酶原和基于事实的过程
公开(公告)号：EP1487867A2
公开(公告)日：2004-12-22
申请号：EP03745086.3
申请日：2003-03-04
申请人： MEDICAL COLLEGE OF OHIO , THE UNIVERSITY OF TOLEDO
发明人： SWIERCZ, Rafal , SELMAN, Steven, H. , JANKUN, Jerzy , SKRZYPCZAK-JANKUN, Ewa , CHOROSTOWSKA-WYNIMKO, Joanna
IPC分类号： C07K14/00 , C07H1/04 , A61K38/00
CPC分类号： C07K14/8132 , A61K38/00
摘要： The present invention is based upon the discovery that modified plasminogen activator inhibitor type-I (PAI-1) in which two or more amino acid residues that do not contain a sulfliydryl group have been replaced with amino acid residues that contain a sulfhydryl group and, therefore, forms intramolecular disulfide bonds, have increased in vivo half-life. Also disclosed are the modified PAI-1 proteins, derivatives and analogs thereof, specific antibodies, nucleic acid molecules and host cells. Methods for producing modified PAI-1, derivatives and analogs are also provided. The invention further relates to Therapeutics, pharmaceutical compositions and method of using the composition for treatment. The invention may be used to inhibit angiogenesis in a subject, thereby treating diseases or conditions associated with undesired angiogenesis and cell proliferation. Such conditions include psoriasis, chronic inflammation, tumor invasion and metastasis and conditions in which angiogenesis is pathogenic. The modified PAI-1 molecules of the present invention are useful for the treatment, prophylaxis, management and amelioration of cardiovascular diseases such as, but not limited to those that are related to hyerfibrinolysis, hemophilia, and vessel leakage syndrome.

5. 发明公开

EP2150273A2 MODIFIED PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 MOLECULE AND METHODS BASED THEREON 审中-公开
标题翻译：修饰的疟原虫激活抑制剂1型分子及其基于方法
公开(公告)号：EP2150273A2
公开(公告)日：2010-02-10
申请号：EP08826564.0
申请日：2008-04-24
申请人： The University of Toledo
发明人： JANKUN, Jerzy , SKRZYPCZAK-JANKUN, Ewa , SELMAN, Steven, H.
IPC分类号： A61K38/55
CPC分类号： C07K14/8132 , A61K38/00
摘要： The present invention relates to a modified plasminogen activator inhibitor type- 1 (PAI-1) molecule that displays an increased in vivo half-life of the active form of PAI- 1, but is deficient in one or more functional activities as compared to the wild-type PAI- 1 protein. The modified PAI-1 molecule that displays an increased half-life further displays at least one of the following funtional characteristics: (i) decreased binding activity to at least one of the following molecules: urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA) and vitronectin (Vn); and (ii) decreased specific activity against at least one of the following molecules: uPA, tPA and Vn. The invention further relates to pharmaceutical compositions comprising modified PAI-I molecules and methods of using these pharmaceutical compositions for treatment.
摘要翻译：本发明涉及显示PAI-1的活性形式的增加的体内半衰期但与一种或多种功能活性相比缺乏一种或多种功能活性的修饰的纤溶酶原激活物抑制剂-1型（PAI-1）分子野生型PAI-1蛋白。表现出增加的半衰期的改性PAI-1分子进一步显示至少一种以下功能特征：（i）与至少一种以下分子的结合活性降低：尿激酶纤溶酶原激活物（uPA），组织纤溶酶原激活物（ tPA）和玻连蛋白（Vn）; 和（ii）针对至少一种以下分子的特异性活性降低：uPA，tPA和Vn。本发明还涉及包含修饰的PAI-1分子的药物组合物以及使用这些药物组合物进行治疗的方法。

6. 发明授权

EP1487867B1 MODIFIED PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 AND METHODS BASED THEREON 有权
标题翻译：改性型纤溶酶原和基于事实的过程
公开(公告)号：EP1487867B1
公开(公告)日：2009-01-21
申请号：EP03745086.3
申请日：2003-03-04
申请人： MEDICAL COLLEGE OF OHIO , The University of Toledo
发明人： SWIERCZ, Rafal , SELMAN, Steven, H. , JANKUN, Jerzy , SKRZYPCZAK-JANKUN, Ewa , CHOROSTOWSKA-WYNIMKO, Joanna
IPC分类号： C07K14/00 , C07H1/04 , A61K38/00
CPC分类号： C07K14/8132 , A61K38/00
摘要： The present invention is based upon the discovery that modified plasminogen activator inhibitor type-I (PAI-1) in which two or more amino acid residues that do not contain a sulfliydryl group have been replaced with amino acid residues that contain a sulfhydryl group and, therefore, forms intramolecular disulfide bonds, have increased in vivo half-life. Also disclosed are the modified PAI-1 proteins, derivatives and analogs thereof, specific antibodies, nucleic acid molecules and host cells. Methods for producing modified PAI-1, derivatives and analogs are also provided. The invention further relates to Therapeutics, pharmaceutical compositions and method of using the composition for treatment. The invention may be used to inhibit angiogenesis in a subject, thereby treating diseases or conditions associated with undesired angiogenesis and cell proliferation. Such conditions include psoriasis, chronic inflammation, tumor invasion and metastasis and conditions in which angiogenesis is pathogenic. The modified PAI-1 molecules of the present invention are useful for the treatment, prophylaxis, management and amelioration of cardiovascular diseases such as, but not limited to those that are related to hyerfibrinolysis, hemophilia, and vessel leakage syndrome.

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