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1. 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。

2. 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。

3. 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.

4. 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。

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

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。

7. 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。

8. 发明授权

US5622862A Assay systems for trkB neurotrophin activity 失效
标题翻译： trkB神经营养因子活性检测系统
公开(公告)号：US5622862A
公开(公告)日：1997-04-22
申请号：US339578
申请日：1994-11-14
申请人： Stephen P. Squinto , David Glass , Thomas H. Aldrich , Peter DiStefano , Trevor Stitt , Mark E. Furth , George D. Yancopoulos
发明人： Stephen P. Squinto , David Glass , Thomas H. Aldrich , Peter DiStefano , Trevor Stitt , Mark E. Furth , George D. Yancopoulos
IPC分类号： A61K38/00 , C07K14/71 , C12N15/00 , C12N5/10
CPC分类号： C07K14/71 , A61K38/00 , G01N2333/475
摘要： The present invention provides for assay systems that may be used to detect and/or measure neurotrophin activity or to identify agents that exhibit neurotrophin-like activity, and for methods of using such assay systems. It is based, at least in part, on the discovery that the trkB protooncogene encodes a tyrosine kinase receptor that may serve as a functional binding protein for BDNF and NT-3. Such assay systems may be of particular value in identifying new neurotrophins or agents with neurotrophin-like activity. In various embodiments, the assay systems and methods of the invention may be used to detect and/or measure the binding of neurotrophin to trkB, either using direct binding studies or the detection of the secondary affects of trkB/neurotrophin binding. The present invention also has diagnostic and therapeutic utilities. In particular embodiments of the invention, methods of detecting aberrancies in trkB function or expression may be used in the diagnosis of neurological disorders. In other embodiments, manipulation of the trkB/neurotrophin interaction may be used in the treatment of neurological disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (Lou Gehrig's disease).
摘要翻译：本发明提供了可用于检测和/或测量神经营养因子活性或鉴定表现出神经营养因子样活性的试剂的测定系统，以及使用该测定系统的方法。至少部分基于trkB原癌基因编码可能作为BDNF和NT-3的功能性结合蛋白的酪氨酸激酶受体的发现。鉴定新的神经营养蛋白或具有神经营养蛋白样活性的药剂时，这种测定系统可能是特别有价值的。在各种实施方案中，本发明的测定系统和方法可以用于使用直接结合研究或trkB /神经营养因子结合的次级影响的检测来检测和/或测量神经营养因子与trkB的结合。本发明还具有诊断和治疗用途。在本发明的具体实施方案中，检测trkB功能或表达异常的方法可用于诊断神经障碍。在其它实施方案中，trkB /神经营养因子相互作用的操作可用于治疗神经障碍，包括阿尔茨海默病，帕金森氏病和肌萎缩性侧索硬化（Lou Gehrig's disease）。

9. 发明申请

US20100233803A1 Fusion Polypeptides Capable of Activating Receptors 有权
标题翻译：融合多肽能激活受体
公开(公告)号：US20100233803A1
公开(公告)日：2010-09-16
申请号：US12466606
申请日：2009-05-15
申请人： James P. Fandl , Gang Chen , Nicholas J. Papadopoulos , Thomas H. Aldrich
发明人： James P. Fandl , Gang Chen , Nicholas J. Papadopoulos , Thomas H. Aldrich
IPC分类号： C12N5/071 , C12N5/07 , C07K16/18
CPC分类号： C07K14/71 , C07H21/04 , C07K16/2863 , C07K2317/31 , C07K2317/52 , C07K2317/622 , C07K2317/75 , C07K2319/30 , C12P21/02
摘要： A fusion polypeptide comprising (A)x-M-(A′)y, wherein A and A′ are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A′ may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different ScFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.
摘要翻译：包含（A）x-M-（A'）y的融合多肽，其中A和A'是能够结合靶受体的多肽。本发明的融合多肽形成激活靶受体的多聚体蛋白。 A和A'可以各自为衍生自靶受体（例如相同或不同ScFv片段）的特异性抗体的抗体或片段，和/或能够结合靶蛋白质的配体或配体片段或衍生物，M为多聚化组分，X和Y独立地为1-10之间的数。

10. 发明授权

US08298532B2 Fusion polypeptides capable of activating receptors 有权
标题翻译：能够激活受体的融合多肽
公开(公告)号：US08298532B2
公开(公告)日：2012-10-30
申请号：US12466606
申请日：2009-05-15
申请人： James P. Fandl , Gang Chen , Nicholas J. Papadopoulos , Thomas H. Aldrich
发明人： James P. Fandl , Gang Chen , Nicholas J. Papadopoulos , Thomas H. Aldrich
IPC分类号： C07K16/28 , A61K39/395
CPC分类号： C07K14/71 , C07H21/04 , C07K16/2863 , C07K2317/31 , C07K2317/52 , C07K2317/622 , C07K2317/75 , C07K2319/30 , C12P21/02
摘要： A fusion polypeptide comprising (A)x-M-(A′)y, wherein A and A′ are each polypeptides capable of binding a target receptor. The fusion polypeptides of the invention form multimeric proteins which activate the target receptor. A and A′ may be each be an antibody or fragment derived from an antibody specific for a target receptor, such as the same or different scFv fragments, and/or a ligand or ligand fragment or derivative capable of binding the target protein, M is a multimerizing component, and X and Y are independently a number between 1-10.
摘要翻译：包含（A）x-M-（A'）y的融合多肽，其中A和A'是能够结合靶受体的多肽。本发明的融合多肽形成激活靶受体的多聚体蛋白。 A和A'可以各自为来自对靶受体特异的抗体的抗体或片段，例如相同或不同的scFv片段，和/或能够结合靶蛋白的配体或配体片段或衍生物，M是多聚化组分，X和Y独立地为1-10之间的数。

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