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1. 发明授权

US07063840B2 TIE-2 ligands, methods of making and uses thereof 失效
公开(公告)号：US07063840B2
公开(公告)日：2006-06-20
申请号：US10179615
申请日：2002-06-24
申请人： Samuel Davis , Joanne Bruno , Mitchell Goldfarb , Thomas H. Aldrich , Peter C. Maisonpierre , Czeslaw Radziejewski , Pamela F. Jones , George D. Yancopoulos
发明人： Samuel Davis , Joanne Bruno , Mitchell Goldfarb , Thomas H. Aldrich , Peter C. Maisonpierre , Czeslaw Radziejewski , Pamela F. Jones , George D. Yancopoulos
IPC分类号： C07K16/24 , A61K39/395
CPC分类号： C07K14/515 , A61K38/00 , C07K2319/00
摘要： The present invention provides for an isolated nucleic acid molecule encoding a human TIE-2 ligand. In addition, the invention provides for a receptor body which specifically binds a human TIE-2 ligand. The invention also provides an antibody which specifically binds a human TIE-2 ligand. The invention further provides for an antagonist of human TIE-2. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor, a method of blocking the growth or differentiation of a cell expressing the TIE-2 receptor and a method of attenuating or preventing tumor growth in a human.

2. 发明授权

US06645484B1 Method of blocking blood vessel growth using tie-2 ligand 2 有权
标题翻译：使用tie-2配体阻断血管生长的方法2
公开(公告)号：US06645484B1
公开(公告)日：2003-11-11
申请号：US09689020
申请日：2000-10-12
申请人： Samuel Davis , JoAnne Bruno , Mitchell Goldfarb , Thomas H. Aldrich , Peter C. Maisonpierre , Czeslaw Radziejewski , Pamela F. Jones , George D. Yancopoulos
发明人： Samuel Davis , JoAnne Bruno , Mitchell Goldfarb , Thomas H. Aldrich , Peter C. Maisonpierre , Czeslaw Radziejewski , Pamela F. Jones , George D. Yancopoulos
IPC分类号： A61K3819
CPC分类号： C07K14/515 , A61K38/00 , C07K2319/00
摘要： The present invention provides for an isolated nucleic acid molecule encoding a human TIE-2 ligand. In addition, the invention provides for a receptor body which specifically binds a human TIE-2 ligand. The invention also provides an antibody which specifically binds a human TIE-2 ligand. The invention further provides for an antagonist of human TIE-2. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor, a method of blocking the growth or differentiation of a cell expressing the TIE-2 receptor and a method of attenuating or preventing tumor growth in a human.
摘要翻译：本发明提供了编码人TIE-2配体的分离的核酸分子。此外，本发明提供了特异性结合人TIE-2配体的受体体。本发明还提供了特异性结合人TIE-2配体的抗体。本发明进一步提供人TIE-2的拮抗剂。本发明还提供治疗组合物以及阻断血管生长的方法，促进新生血管形成的方法，促进表达TIE-2受体的细胞的生长或分化的方法，阻断生长或分化的方法的表达TIE-2受体的细胞以及减弱或预防人类肿瘤生长的方法。

3. 发明授权

US5879672A Tie-2 ligand 1 失效
标题翻译： Tie-2配体1
公开(公告)号：US5879672A
公开(公告)日：1999-03-09
申请号：US348492
申请日：1994-12-02
申请人： Samuel Davis , Thomas H. Aldrich , George D. Yancopoulos
发明人： Samuel Davis , Thomas H. Aldrich , George D. Yancopoulos
IPC分类号： C12N15/12 , A61K38/00 , A61K38/17 , A61P43/00 , C07K14/47 , C07K14/515 , C07K16/28 , C12N5/02 , C12N5/07 , C12N15/85 , C12P21/00 , A61K38/19 , C07K14/52
CPC分类号： C07K14/515 , A61K38/00 , C07K2319/00
摘要： The present invention provides for an isolated nucleic acid molecule encoding human TIE-2 ligand. In addition, the invention provides for a receptor body which specifically binds human TIE-2 ligand. The invention also provides an antibody which specifically binds human TIE-2 ligand. The invention further provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization and a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor.
摘要翻译：本发明提供了编码人TIE-2配体的分离的核酸分子。此外，本发明提供了特异性结合人TIE-2配体的受体体。本发明还提供了特异性结合人TIE-2配体的抗体。本发明进一步提供治疗组合物以及阻断血管生长的方法，促进新生血管形成的方法和促进表达TIE-2受体的细胞的生长或分化的方法。

4. 发明授权

US5521073A TIE-2 ligand, and method of making 失效
标题翻译： TIE-2配体及其制备方法
公开(公告)号：US5521073A
公开(公告)日：1996-05-28
申请号：US330261
申请日：1994-10-27
申请人： Samuel Davis , Thomas H. Aldrich , George D. Yancopoulos
发明人： Samuel Davis , Thomas H. Aldrich , George D. Yancopoulos
IPC分类号： A61K38/00 , C07K14/515 , C12N15/12 , C07K14/00
CPC分类号： C07K14/515 , A61K38/00 , C07K2319/00
摘要： The present invention provides for an isolated nucleic acid molecule encoding human TIE-2 ligand. In addition, the invention provides for a receptor body which specifically binds human TIE-2 ligand. The invention also provides an antibody which specifically binds human TIE-2 ligand. The invention further provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization and a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor.
摘要翻译：本发明提供了编码人TIE-2配体的分离的核酸分子。此外，本发明提供了特异性结合人TIE-2配体的受体体。本发明还提供了特异性结合人TIE-2配体的抗体。本发明进一步提供治疗组合物以及阻断血管生长的方法，促进新生血管形成的方法和促进表达TIE-2受体的细胞的生长或分化的方法。

5. 发明授权

US06433143B1 Tie-2 ligands 有权
标题翻译： Tie-2配体
公开(公告)号：US06433143B1
公开(公告)日：2002-08-13
申请号：US08817318
申请日：1999-09-16
申请人： Samuel Davis , Joanne Bruno , Mitchell Goldfarb , Thomas H. Aldrich , Peter C. Maisonpierre , Czeslaw Radziejewski , Pamela F. Jones , George D. Yancopoulos
发明人： Samuel Davis , Joanne Bruno , Mitchell Goldfarb , Thomas H. Aldrich , Peter C. Maisonpierre , Czeslaw Radziejewski , Pamela F. Jones , George D. Yancopoulos
IPC分类号： C07K1452
CPC分类号： C07K14/515 , A61K38/00 , C07K2319/00
摘要： The present invention provides for an isolated nucleic acid molecule encoding a human TIE-2 ligand. In addition, the invention provides for a receptor body, which specifically binds a human TIE-2 ligand. The invention also provides an antibody that specifically binds a human TIE-2 ligand. The invention further provides for an antagonist of human TIE-2. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor, a method of blocking the growth or differentiation of a cell expressing the TIE-2 receptor and a method of attenuating or preventing tumor growth in a human.
摘要翻译：本发明提供了编码人TIE-2配体的分离的核酸分子。此外，本发明提供了特异性结合人TIE-2配体的受体体。本发明还提供了特异性结合人TIE-2配体的抗体。本发明进一步提供人TIE-2的拮抗剂。本发明还提供治疗组合物以及阻断血管生长的方法，促进新生血管形成的方法，促进表达TIE-2受体的细胞的生长或分化的方法，阻断生长或分化的方法的表达TIE-2受体的细胞以及减弱或预防人类肿瘤生长的方法。

6. 发明授权

US5747033A Method of enhancing the biological activity of Eph family ligands 失效
标题翻译：提高Eph家族配体生物活性的方法
公开(公告)号：US5747033A
公开(公告)日：1998-05-05
申请号：US299567
申请日：1994-09-01
申请人： Samuel Davis , Nicholas W. Gale , Thomas H. Aldrich , Peter C. Maisonpierre , Mitchell Goldfarb , George D. Yancopoulos
发明人： Samuel Davis , Nicholas W. Gale , Thomas H. Aldrich , Peter C. Maisonpierre , Mitchell Goldfarb , George D. Yancopoulos
IPC分类号： C07K14/47 , C07K14/71 , C12N9/12 , C12Q1/00 , C12Q1/02 , G01N33/50 , G01N33/573 , G01N33/68 , A61K38/16 , A61K39/44 , C07K14/705 , C07K19/00
CPC分类号： C12N9/1205 , C07K14/4702 , C07K14/71 , C12Q1/00 , C12Q1/02 , G01N33/50 , G01N33/573 , G01N33/6896 , Y10S530/839
摘要： Novel ligands that bind Eph family receptors are identified, and methods for making the soluble ligands in biologically active form are described. cDNA clones encoding these novel proteins enable production of the recombinant proteins, which are useful to support neuronal and other receptor-bearing cell populations.
摘要翻译：鉴定了结合Eph家族受体的新型配体，并描述了制备可生物活性形式的可溶性配体的方法。编码这些新蛋白质的cDNA克隆能够产生重组蛋白，其可用于支持神经元和其他受体携带细胞群体。

7. 发明授权

US6166185A Antibodies to human TIE-2 ligands 有权
标题翻译：人类TIE-2配体的抗体
公开(公告)号：US6166185A
公开(公告)日：2000-12-26
申请号：US162437
申请日：1998-09-28
申请人： Samuel Davis , JoAnne Bruno , Mitchell Goldfarb , Thomas H. Aldrich , Peter C. Maisonpierre , Czeslaw Radziejewski , Pamela F. Jones , George D. Yancopoulos
发明人： Samuel Davis , JoAnne Bruno , Mitchell Goldfarb , Thomas H. Aldrich , Peter C. Maisonpierre , Czeslaw Radziejewski , Pamela F. Jones , George D. Yancopoulos
IPC分类号： G01N33/50 , A61K38/00 , A61K38/17 , A61K39/395 , A61K47/48 , A61K48/00 , A61K51/00 , A61P9/10 , A61P29/00 , A61P31/04 , A61P35/00 , C07H21/04 , C07K20060101 , C07K14/47 , C07K14/515 , C07K14/705 , C07K16/28 , C07K19/00 , C12N20060101 , C12N5/06 , C12N5/10 , C12N15/00 , C12N15/02 , C12N15/09 , C12N15/12 , C12N15/19 , C12N15/62 , C12N15/63 , C12P21/02 , C12P21/08 , C12R1/91 , G01N33/53 , C07K16/18 , C07K16/22 , C07K16/24
CPC分类号： C07K14/515 , A61K38/00 , C07K2319/00
摘要： The present invention provides for an isolated nucleic acid molecule encoding a human TIE-2 ligand. In addition, the invention provides for a receptor body which specifically binds a human TIE-2 ligand. The invention also provides an antibody which specifically binds a human TIE-2 ligand. The invention further provides for an antagonist of human TIE-2. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE-2 receptor, a method of blocking the growth or differentiation of a cell expressing the TIE-2 receptor and a method of attenuating or preventing tumor growth in a human.
摘要翻译：本发明提供了编码人TIE-2配体的分离的核酸分子。此外，本发明提供了特异性结合人TIE-2配体的受体体。本发明还提供了特异性结合人TIE-2配体的抗体。本发明进一步提供人TIE-2的拮抗剂。本发明还提供治疗组合物以及阻断血管生长的方法，促进新生血管形成的方法，促进表达TIE-2受体的细胞的生长或分化的方法，阻断生长或分化的方法的表达TIE-2受体的细胞以及减弱或预防人类肿瘤生长的方法。

8. 发明授权

US08029791B2 Modified chimeric polypeptides with improved pharmacokinetic properties 有权
标题翻译：具有改善的药代动力学性质的修饰的嵌合多肽
公开(公告)号：US08029791B2
公开(公告)日：2011-10-04
申请号：US12102666
申请日：2008-04-14
申请人： Nicholas J. Papadopoulos , Samuel Davis , George D. Yancopoulos
发明人： Nicholas J. Papadopoulos , Samuel Davis , George D. Yancopoulos
IPC分类号： A61K38/18 , C07K14/71
CPC分类号： C07K14/71 , A61K38/00 , C07K16/22 , C07K19/00 , C07K2319/00 , C07K2319/30
摘要： Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal.
摘要翻译：公开了具有改善的药代动力学的修饰的嵌合多肽。具体地，公开了已经以改善其药代动力学特征的方式修饰的修饰的嵌合Flt1受体多肽。还公开了制备和使用修饰的多肽的方法，包括但不限于使用修饰的多肽来降低或抑制哺乳动物的血浆渗透和/或血管通透性。

9. 发明授权

US07524499B2 Modified chimeric polypeptides with improved pharmacokinetic properties 有权
标题翻译：具有改善的药代动力学性质的修饰的嵌合多肽
公开(公告)号：US07524499B2
公开(公告)日：2009-04-28
申请号：US12102648
申请日：2008-04-14
申请人： Nicholas J. Papadopoulos , Samuel Davis , George D. Yancopoulos
发明人： Nicholas J. Papadopoulos , Samuel Davis , George D. Yancopoulos
IPC分类号： A61K38/18 , C07K14/71 , C12N15/62
CPC分类号： C07K14/71 , A61K38/00 , C07K16/22 , C07K19/00 , C07K2319/00 , C07K2319/30
摘要： Modified chimeric polypeptides with improved pharmacokinetics are disclosed. Specifically, modified chimeric Flt1 receptor polypeptides that have been modified in such a way as to improve their pharmacokinetic profile are disclosed. Also disclosed are methods of making and using the modified polypeptides including but not limited to using the modified polypeptides to decrease or inhibit plasma leakage and/or vascular permeability in a mammal.
摘要翻译：公开了具有改善的药代动力学的修饰的嵌合多肽。具体地，公开了已经以改善其药代动力学特征的方式修饰的修饰的嵌合Flt1受体多肽。还公开了制备和使用修饰的多肽的方法，包括但不限于使用修饰的多肽来降低或抑制哺乳动物的血浆渗透和/或血管通透性。

10. 发明授权

US06825008B2 Expressed ligand—vascular intercellular signalling molecule 有权
标题翻译：表达配体 - 血管细胞间信号分子
公开(公告)号：US06825008B2
公开(公告)日：2004-11-30
申请号：US10225060
申请日：2002-08-21
申请人： Samuel Davis , George D. Yancopoulos
发明人： Samuel Davis , George D. Yancopoulos
IPC分类号： G12P2106
CPC分类号： C12N15/8509 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2227/30 , A01K2267/01 , A01K2267/03 , A01K2267/0331 , A01K2267/0375 , A01K2267/0381 , A61K38/00 , C07K14/515 , C07K14/71 , C07K2319/00 , C07K2319/02
摘要： The present invention provides for a modified TIE-2 ligand which has been altered by addition, deletion or substitution of one or more amino acids, or by way of tagging, with for example, the Fc portion of human IgG-1, but which retains its ability to bind the TIE-2 receptor. The invention further provides for a modified TIE-2 ligand which is a chimeric TIE-2 ligand comprising at least a portion of a first TIE-2 ligand and a portion of a second TIE-2 ligand which is different from the first. In a specific embodiment, the invention further provides for a chimeric TIE ligand comprising at least a portion of TIE-2 Ligand-1 and a portion of TIE-2 Ligand-2. In addition the present invention provides for isolated nucleic acid molecule encoding the modified TIE-2 ligands described. The invention also provides for therapeutic compositions as well as a method of blocking blood vessel growth, a method of promoting neovascularization, a method of promoting the growth or differentiation of a cell expressing the TIE receptor, a method of blocking the growth or differentiation of a cell expressing the TIE receptor and a method of attenuating or preventing tumor growth in a human.
摘要翻译：本发明提供了修饰的TIE-2配体，其通过添加，缺失或取代一个或多个氨基酸，或通过标记，例如，人IgG-1的Fc部分，但保留其结合TIE-2受体的能力。本发明还提供了修饰的TIE-2配体，其是包含与第一TIE-2配体不同的第一TIE-2配体和第二TIE-2配体的至少一部分的嵌合TIE-2配体。在一个具体实施方案中，本发明还提供了包含TIE-2配体-1的至少一部分和TIE-2配体-2的一部分的嵌合TIE配体。此外，本发明提供了编码所述修饰的TIE-2配体的分离的核酸分子。本发明还提供治疗组合物以及阻断血管生长的方法，促进新生血管形成的方法，促进表达TIE受体的细胞的生长或分化的方法，阻止生长或分化的方法表达TIE受体的细胞和减弱或预防人类肿瘤生长的方法。

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