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1. 发明申请

WO2004003211A1 BISPECIFIC ANTIBODIES THAT BIND TO VEGF RECEPTORS 审中-公开
标题翻译：与VEGF受体结合的双重抗体
公开(公告)号：WO2004003211A1
公开(公告)日：2004-01-08
申请号：PCT/US2002/041372
申请日：2002-12-24
申请人： IMCLONE SYSTEMS INCORPORATED , ZHU, Zhenping
发明人： ZHU, Zhenping
IPC分类号： C12P12/08
CPC分类号： C07K16/2863 , C07K2317/21 , C07K2317/31 , C07K2317/55 , C07K2317/622 , C07K2317/626
摘要： The present invention is directed to production of antigen-binding proteins that bind specifically to an extracellular domains of two different VEGF receptors. The bispecific antigen-binding proteins block activation of the VEGF receptors and are used to reduce or inhibit VEGF-induced cellular functions such as mitogenesis of vascular endothelial cells and migration of leukemia cells. The antigen-binding proteins of the present invention can be monovalent or multivalent, have antigen-binding sites consisting of immunoglobulin heavy chain and light chain variable domains and may further include immunoglobulin constant domains.
摘要翻译：本发明涉及特异性结合两种不同VEGF受体的细胞外结构域的抗原结合蛋白的制备。双特异性抗原结合蛋白阻断VEGF受体的活化，并用于降低或抑制VEGF诱导的细胞功能，如血管内皮细胞的有丝分裂和白血病细胞的迁移。本发明的抗原结合蛋白可以是一价或多价的，具有由免疫球蛋白重链和轻链可变区组成的抗原结合位点，并且还可以包括免疫球蛋白恒定结构域。

2. 发明申请

WO2003075840A3 HUMAN ANTIBODIES SPECIFIC TO KDR AND USES THEREOF 审中-公开
公开(公告)号：WO2003075840A3
公开(公告)日：2003-09-18
申请号：PCT/US2003/006459
申请日：2003-03-04
申请人： IMCLONE SYSTEMS INCORPORATED , ZHU, Zhenping
发明人： ZHU, Zhenping
IPC分类号： C07H21/04
摘要： The invention provides an antibodies that bind to KDR with an affinity comparable to or higher than human VEGF, and that neutralizes activation of KDR . Antibodies include whole immunoglobulins, monovalent Fabs and single chain antibodies, multivalent single chain antibodies, diabodies, triabodies, and single domain antibodies. The invention further provides nucleic acids and host cells that encode and express these antibodies. The invention further provides a method of neutralizing the activation of KDR, a method of inhibiting angiogenesis in a mammal and a method of inhibiting tumor growth in a mammal.

3. 发明申请

WO2010056893A1 HUMANIZATION AND AFFINITY-OPTIMIZATION OF ANTIBODIES 审中-公开
标题翻译：抗体的人类和亲和力优化
公开(公告)号：WO2010056893A1
公开(公告)日：2010-05-20
申请号：PCT/US2009/064247
申请日：2009-11-12
申请人： IMCLONE LLC , HAIDAR, Jaafar, Nassar Sleiman , YUAN, Qing-an , ZHU, Zhenping
发明人： HAIDAR, Jaafar, Nassar Sleiman , YUAN, Qing-an , ZHU, Zhenping
IPC分类号： C07K16/46 , C12P21/08 , G01N33/48
CPC分类号： C07K16/464 , C07K16/005 , C07K16/2863 , C07K2317/24 , C07K2317/55
摘要： In an efficient selection of higher affinity binders for an antibody humanization strategy, original CDRs are grafted, but no homology modeling is required to determine the key residues in a framework region. One human variable region heavy chain or "VH' and one variable region light chain or 'VL" germline segments show characteristics of high expression in E. coli as a universal template. Key residues in the framework scaffold were determined by screening of available antibody crystal structure data as well as published documents that described the refinements of a specific mouse humanization project. Diversified residues that represent either human antibody selections or mouse selections were integrated into those key framework positions that were assumed to be important in either supporting CDRs or affecting the overall domain structure. A phage display Fab library was used to screen functional reshaped antibodies, which facilitates the isolation of well-maintained clones in a standard panning.
摘要翻译：在用于抗体人源化策略的高亲和力结合物的有效选择中，原始CDR被移植，但是不需要同源建模来确定框架区域中的关键残基。一个人可变区重链或“VH”和一个可变区轻链或“VL”种系显示了在大肠杆菌中作为通用模板的高表达特征。通过筛选可获得的抗体晶体结构数据以及描述特定小鼠人源化项目的改进的公开文献来确定框架支架中的关键残基。代表人抗体选择或小鼠选择的多样化残基被整合到那些被认为在支持CDR或影响整个结构域结构中重要的关键框架位置。使用噬菌体展示Fab文库筛选功能重整抗体，这有助于在标准淘选中分离良好维持的克隆。

4. 发明申请

WO2008130704A3 PDGFRß-SPECIFIC INHIBITORS 审中-公开
标题翻译： PDGFRβ特异性抑制剂
公开(公告)号：WO2008130704A3
公开(公告)日：2008-12-24
申请号：PCT/US2008005137
申请日：2008-04-17
申请人： IMCLONE SYSTEMS INC , ZHU ZHENPING , SHEN JUQUN
发明人： ZHU ZHENPING , SHEN JUQUN
IPC分类号： C07K16/28 , A61K39/395 , A61P35/00
CPC分类号： C07K16/2863 , A61K39/3955 , A61K41/00 , A61K45/06 , A61K2039/505 , A61K2039/507 , C07K2317/21 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/92 , A61K2300/00
摘要： The invention is directed to novel PDGFRß-specific antagonists. The antagonists include antibodies, which can be bispecific. The antibodies are used to reduce or inhibit tumor growth and or to treat an angiogenic disease. The invention also includes combinations of PDGFRß-specific antagonists with VEGFR antagonists for such treatments. The antagonists can further be administered in combination with other anti- angiogenic or anti-neoplastic drugs.
摘要翻译：本发明涉及新型PDGFRβ特异性拮抗剂。拮抗剂包括可以是双特异性的抗体。抗体用于减少或抑制肿瘤生长和/或治疗血管生成疾病。本发明还包括PDGFRβ特异性拮抗剂与用于这种治疗的VEGFR拮抗剂的组合。拮抗剂可以进一步与其它抗血管生成或抗肿瘤药物组合施用。

5. 发明申请

WO03075840A2 HUMAN ANTIBODIES SPECIFIC TO KDR AND USES THEREOF 审中-公开
标题翻译：人类抗体特异性及其用途
公开(公告)号：WO03075840A2
公开(公告)日：2003-09-18
申请号：PCT/US0306459
申请日：2003-03-04
申请人： IMCLONE SYSTEMS INC , ZHU ZHENPING
发明人： ZHU ZHENPING
IPC分类号： C12N15/09 , A61K39/395 , A61K45/00 , A61P35/00 , A61P43/00 , C07K16/28 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , A61K
CPC分类号： C07K16/2863 , A61K2039/505 , C07K2317/21 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/76 , C07K2317/92
摘要： The invention provides antibodies that bind to KDR with an affinity comparable to or higher than human VEGF, and that neutralize activation of KDR. Antibodies include whole immunoglobulins, monovalent Fabs and single chain antibodies, multivalent single chain antibodies, diabodies, triabodies, and single domain antibodies. The invention further provides nucleic acids and host cells that encode and express these antibodies. The invention further provides a method of neutralizing the activation of KDR, a method of inhibiting angiogenesis in a mammal and a method of inhibiting tumor growth in a mammal.
摘要翻译：本发明提供以与人VEGF相当或高于人VEGF的亲和力结合KDR的抗体，并且中和KDR的活化。抗体包括整个免疫球蛋白，单价Fab和单链抗体，多价单链抗体，双抗体，三抗体和单结构域抗体。本发明还提供编码和表达这些抗体的核酸和宿主细胞。本发明还提供了中和KDR活化的方法，抑制哺乳动物血管发生的方法和抑制哺乳动物肿瘤生长的方法。

6. 发明申请

WO0190192A3 BISPECIFIC IMMUNOGLOBULIN-LIKE ANTIGEN BINDING PROTEINS AND METHOD OF PRODUCTION 审中-公开
标题翻译：双抗体免疫抑制蛋白抗体结合蛋白及其生产方法
公开(公告)号：WO0190192A3
公开(公告)日：2003-01-16
申请号：PCT/US0116924
申请日：2001-05-24
申请人： IMCLONE SYSTEMS INC , ZHU ZHENPING
发明人： ZHU ZHENPING
IPC分类号： C12N15/09 , A61K38/00 , A61P9/00 , A61P35/00 , A61P43/00 , C07K16/28 , C07K16/46 , C12P21/02 , C07K16/00 , A61K39/395 , C07K16/30 , C07K16/32 , C07K16/40 , C07K19/00
CPC分类号： C07K16/468 , C07K16/2863 , C07K2317/31 , C07K2317/622
摘要： The present invention is directed to bispecific antigen-binding protein. These bispecific antigen-binding proteins are optimized in their avidity for antigen(s) but maintain their ability to function as a natural antibody, including the ability to activate complement mediated cytotoxicity and antibody dependent cellular toxicity. Natural IgG immunoglobulins are monospecific and bivalent, having two binding domains which are specific for the same epitope. By contrast, and IgG type immunoglobulin of the invention is bispecific and bivalent, having a binding domain on each light chain for one epitope and a binding domain on each heavy chain specific for a second epitope. The design of the present antigen-binding proteins provides for efficient production such that substantially all of the antigen-binding proteins produced are assembled in the desired configuration.
摘要翻译：本发明涉及双特异性抗原结合蛋白。这些双特异性抗原结合蛋白的抗原亲和力优化，但保持其作为天然抗体的功能，包括激活补体介导的细胞毒性和抗体依赖性细胞毒性的能力。天然IgG免疫球蛋白是单特异性和二价的，具有两个相同表位特异性的结合结构域。相比之下，本发明的IgG型免疫球蛋白是双特异性和二价的，在每个轻链上具有针对一个表位的结合结构域和在每个重链上具有针对第二表位的结合结构域。本发明的抗原结合蛋白的设计提供了有效的生产，使得基本上所有产生的抗原结合蛋白都以所需的构型组装。

7. 发明申请

WO2003002144A1 BISPECIFIC ANTIBODIES THAT BIND TO VEGF RECEPTORS 审中-公开
标题翻译：与VEGF受体结合的双重抗体
公开(公告)号：WO2003002144A1
公开(公告)日：2003-01-09
申请号：PCT/US2002/020332
申请日：2002-06-26
申请人： IMCLONE SYSTEMS INCORPORATED , ZHU, Zhenping
发明人： ZHU, Zhenping
IPC分类号： A61K39/395
CPC分类号： C07K16/2863 , A61K2039/505 , C07K2317/31 , C07K2317/56 , C07K2317/565 , C07K2317/622 , C07K2317/626 , C07K2317/76
摘要： The present invention is directed to production of antigen-binding proteins that bind specifically to an extracellular domains of two different VEGF receptors, The bispecific antigen-binding proteins block activation of the VEGF receptors and are used to reduce or inhibit VEGF-induced cellular functions such as mitogenesis of vascular endothelial cells and migration of leukemia cells. The antigen-binding proteins of the present invention can be monovalent or multivalent, have antigen-binding sites consisting of immunoglobulin heavy chain and light chain variable domains and may further include immunoglobulin constant domains.
摘要翻译：本发明涉及特异性结合两种不同VEGF受体的细胞外结构域的抗原结合蛋白的生产。双特异性抗原结合蛋白阻断VEGF受体的活化，并用于降低或抑制VEGF诱导的细胞功能，例如作为血管内皮细胞的有丝分裂和白血病细胞的迁移。本发明的抗原结合蛋白可以是一价或多价的，具有由免疫球蛋白重链和轻链可变区组成的抗原结合位点，并且还可以包括免疫球蛋白恒定结构域。

8. 发明申请

WO2012069466A1 MULTISPECIFIC MOLECULES 审中-公开
标题翻译：多重分子
公开(公告)号：WO2012069466A1
公开(公告)日：2012-05-31
申请号：PCT/EP2011/070668
申请日：2011-11-22
申请人： NOVARTIS AG , LEI, Ming , LI, Jing , ZHOU, Li , ZHU, Zhenping
发明人： LEI, Ming , LI, Jing , ZHOU, Li , ZHU, Zhenping
IPC分类号： C07K16/28 , C07K16/32
CPC分类号： C07K16/468 , C07K16/00 , C07K16/2863 , C07K16/32 , C07K2317/31 , C07K2317/53 , C07K2317/60 , C07K2317/64
摘要： The present invention is directed to multi-specific/multivalent molecules of novel formats. The molecules with the formats of the present invention have desired yield and thermostability. The present invention also includes methods of producing and using the molecules described herein.
摘要翻译：本发明涉及新型的多特异性/多价分子。具有本发明形式的分子具有期望的产率和热稳定性。本发明还包括生产和使用本文所述分子的方法。

9. 发明申请

WO2007095338A2 FUNCTIONAL ANTIBODIES 审中-公开
标题翻译：功能抗体
公开(公告)号：WO2007095338A2
公开(公告)日：2007-08-23
申请号：PCT/US2007004051
申请日：2007-02-15
申请人： IMCLONE SYSTEMS INC , ZHU ZHENPING
发明人： ZHU ZHENPING
CPC分类号： C07K16/2863 , C07K16/00 , C07K16/468 , C07K2317/21 , C07K2317/50 , C07K2317/55 , C07K2317/569 , C07K2317/622 , C07K2317/626 , C07K2317/64 , C07K2317/76 , C07K2317/92 , C07K2319/30
摘要： The invention is directed to novel antibodies, which comprise single domain binding sites. The antibodies can be bivalent or multivalent, and can be bispecific. The invention is further directed to monospecific and bispecific antibodies that bind to mPDGFRa. The antibodies can be administered alone or in combination with anti- angiogenic or anti-neoplastic drugs.
摘要翻译：本发明涉及包含单结构域结合位点的新型抗体。抗体可以是二价或多价的，并且可以是双特异性的。本发明还涉及与mPDGFRa结合的单特异性和双特异性抗体。抗体可以单独施用或与抗血管生成或抗肿瘤药联合施用。

10. 发明申请

WO2006020258A3 NOVEL TETRAVALENT BISPECIFIC ANTIBODY 审中-公开
标题翻译：新的四价双特异性抗体
公开(公告)号：WO2006020258A3
公开(公告)日：2006-10-12
申请号：PCT/US2005025472
申请日：2005-07-18
申请人： IMCLONE SYSTEMS INC , ZHU ZHENPING
发明人： ZHU ZHENPING
IPC分类号： C12P21/08 , A61K39/395 , C07K16/28 , C07K16/46
CPC分类号： C07K16/2863 , A61K2039/505 , C07K2317/31 , C07K2317/622 , C07K2317/626 , C07K2317/73 , C07K2317/732 , C07K2317/77 , C07K2317/92
摘要： The invention is directed to novel tetravalent antibodies, which are preferably bi-specific. The tetravalent bispecific antibodies can be efficiently expressed in prokaryotic and eukaryotic cells, and are useful in therapeutic and diagnostic methods. The invention further describes administration of the antibodies, either alone or in combination with antiangiogenic or anti-neoplastic drugs to inhibit tumor growth and/or angiogenesis.
摘要翻译：本发明涉及新颖的四价抗体，其优选是双特异性的。四价双特异性抗体可以在原核和真核细胞中有效表达，并且可用于治疗和诊断方法。本发明进一步描述了抗体的单独施用或与抗血管生成或抗肿瘤药物组合以抑制肿瘤生长和/或血管生成。

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