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1. 发明申请

WO2005042743A8 HUMANIZATION OF ANTIBODIES 审中-公开
标题翻译：抗体人类化
公开(公告)号：WO2005042743A8
公开(公告)日：2013-11-21
申请号：PCT/US2004026953
申请日：2004-08-18
申请人： MEDIMMUNE INC , DALL-ACQUA WILLIAM , DAMSCHRODER MELISSA , WU HERREN
发明人： DALL-ACQUA WILLIAM , DAMSCHRODER MELISSA , WU HERREN
IPC分类号： A61P35/00 , C07H21/04 , C07K16/00 , C07K16/40 , C12N15/13
CPC分类号： C07K16/005 , C07H21/04 , C07K16/40 , C12N15/1037 , C12Q2563/131
摘要： The present invention relates to methods of reengineering or reshaping antibodies to reduce the immunogenicity of the antibodies, while maintaining the immunospecificity of the antibodies for an antigen. In particular, the present invention provides methods of producing antibodies immunospecific for an antigen by synthesizing a combinatorial library comprising complementarity determining regions (CDRs) from a donor antibody fused in frame to framework regions from a sub-bank of framework regions. The present invention also provides antibodies produced by the methods of the invention.
摘要翻译：本发明涉及重新设计或重塑抗体以降低抗体免疫原性的方法，同时保持针对抗原的抗体的免疫特异性。特别地，本发明提供了通过合成包含来自框架区域的子库的框架区域融合的供体抗体的互补决定区（CDR）的组合文库的组合文库来产生针对抗原免疫特异性的抗体的方法。本发明还提供通过本发明的方法制备的抗体。

2. 发明申请

WO2006050166A3 METHODS OF PREVENTING AND TREATING RSV INFECTIONS AND RELATED CONDITIONS 审中-公开
标题翻译：预防和治疗RSV感染的方法及相关条件
公开(公告)号：WO2006050166A3
公开(公告)日：2009-04-09
申请号：PCT/US2005039091
申请日：2005-10-31
申请人： MEDIMMUNE INC , LOSONSKY GENEVIEVE , CONNOR EDWARD M , YOUNG JAMES F , WU HERREN , DALL ACQUA WILLIAM
发明人： LOSONSKY GENEVIEVE , CONNOR EDWARD M , YOUNG JAMES F , WU HERREN , DALL ACQUA WILLIAM
IPC分类号： A61K39/395
CPC分类号： C07K16/1027 , A61K2039/505 , A61K2039/543 , C07K2317/21 , C07K2317/24 , C07K2317/52 , C07K2317/55 , C07K2317/565 , C07K2317/567 , C07K2317/72 , C07K2317/92 , C07K2317/94
摘要： The present invention provides methods for preventing, managing, treating and/or ameliorating a Respiratory Syncytial Virus (RSV) infection (e.g., acute RSV disease, or a RSV upper respiratory tract infection (URI) and/or lower respiratory tract infection (LRI)), otitis media (preferably, stemming from, caused by or associated with a RSV infection, such as a RSV URI and/or LRI), and/or a symptom or respiratory condition relating thereto (e.g., asthma, wheezing, and/or reactive airway disease (RAD)) in a subject, comprising administering to said human an effective amount of one or more antibodies that immunospecifically bind to one or more RSV antigens with a high affinity and/or high avidity. In some embodiments, one or more antibodies comprise a modified IgG constant domain, or FcRn-binding fragment thereof resulting in longer in vivo serum half-life. In particular embodiments the methods of the invention comprising administering to subject an effective amount of one or more modified antibodies that immunospecifically bind to one or more RSV antigens with an association rate (kon) of at least 2 x 105 M-1s-1 and a dissociation rate (koff) of less than 5 x 10-4 S-1.
摘要翻译：本发明提供了用于预防，治疗和/或改善呼吸道合胞病毒（RSV）感染（例如急性RSV疾病或RSV上呼吸道感染（URI））和/或下呼吸道感染（LRI）的方法，），中耳炎（优选来源于，由RSV感染引起或与RSV感染相关联，例如RSV URI和/或LRI），和/或与其相关的症状或呼吸病症（例如，哮喘，喘息和/或反应性气道疾病（RAD）），包括向所述人施用有效量的一种或多种以高亲和力和/或高亲合力免疫特异性结合一种或多种RSV抗原的抗体。在一些实施方案中，一种或多种抗体包含修饰的IgG恒定结构域或其FcRn结合片段，导致更长的体内血清半衰期。在具体实施方案中，本发明的方法包括施用有效量的一种或多种经免疫特异性结合一种或多种具有至少2×10 5 M-1s-1的缔合速率（kon）的RSV抗原的修饰的抗体，以及解离速率（koff）小于5×10-4S-1。

3. 发明申请

WO2009009103A2 CRYSTALS AND STRUCTURE OF HUMAN IgG Fc VARIANT 审中-公开
标题翻译：人IgG Fc变体的晶体和结构
公开(公告)号：WO2009009103A2
公开(公告)日：2009-01-15
申请号：PCT/US2008008482
申请日：2008-07-10
申请人： MEDIMMUNE LLC , DALL ACQUA WILLIAM , OGANESYAN VAHEH , CASAS-FINET JOSE , BRADEN BRADFORD , WU HERREN
发明人： DALL ACQUA WILLIAM , OGANESYAN VAHEH , CASAS-FINET JOSE , BRADEN BRADFORD , WU HERREN
IPC分类号： C07K16/40
CPC分类号： C07K16/2866 , C07K16/00 , C07K2299/00 , C07K2317/24 , C07K2317/55 , C07K2317/72 , C07K2317/92
摘要： The present invention provides crystalline forms of a human IgG Fc variant comprising one or more amino acid residues that provides for enhanced effector function, methods of obtaining such crystals and high-resolution X-ray diffraction structures and atomic structure coordinates. The present invention also provides machine readable media embedded with the three-dimensional atomic structure coordinates of the human IgG Fc variant and methods of using them. The present invention also provides human IgG Gc variants with reduced binding to at least one Fc?R.
摘要翻译：本发明提供了包含提供增强的效应子功能的一个或多个氨基酸残基的人IgG Fc变体的结晶形式，获得此类晶体的方法和高分辨率X射线衍射结构以及原子结构坐标。本发明还提供嵌入有人IgG Fc变体的三维原子结构坐标的机器可读介质及其使用方法。本发明还提供了与至少一个FcγR结合减少的人IgG Gc变体。

4. 发明申请

WO2008100816A9 ANTIBODY LIBRAY DISPLAY BY YEAST CELL PLASMA MEMBRANE 审中-公开
公开(公告)号：WO2008100816A9
公开(公告)日：2008-08-21
申请号：PCT/US2008/053398
申请日：2008-02-08
申请人： MEDIMMUNE, LLC , WU, Herren , GAO, Changshou
发明人： WU, Herren , GAO, Changshou
IPC分类号： A61K39/00 , C12N1/00
摘要： The present invention relates to antibodies or antibody fragments that may be displayed on the extracellular surface of the plasma membrane when expressed in a host cell. The present invention provides libraries comprising a plurality of plasma membrane displayed antibodies and methods of screening the libraries for antibodies or antibody fragments with desired characteristics.

5. 发明申请

WO2008042941A2 HUMANIZED ANTI-EPHB4 ANTIBODIES AND THEIR USE IN TREATMENT OF ONCOLOGY AND VASCULOGENESIS-RELATED DISEASE 审中-公开
标题翻译：人源化抗EPHB4抗体及其在治疗肿瘤和血管造成相关疾病中的应用
公开(公告)号：WO2008042941A2
公开(公告)日：2008-04-10
申请号：PCT/US2007080270
申请日：2007-10-03
申请人： MEDIMMUNE INC , DAMSCHRODER MELISSA , DALL ACQUA WILLIAM , WU HERREN , BOWDEN EMMA T
发明人： DAMSCHRODER MELISSA , DALL ACQUA WILLIAM , WU HERREN , BOWDEN EMMA T
IPC分类号： A61K39/395
CPC分类号： C07K16/2866 , C07K2317/24 , C07K2317/55 , C07K2317/73 , C07K2317/75 , C07K2317/76 , C07K2317/92 , C07K2319/30 , C07K2319/32
摘要： The present invention provides humanized versions of anti-EphB4 mouse monoclonal antibodies. The invention further relates to pharmaceutical compositions, immunotherapeutic compositions, and methods using therapeutic antibodies that bind to the human EphB4 antigen and that may mediate ADCC, CDC, and/or apoptosis for the treatment of human malignancies and vasculogenesis-related disorders and diseases.
摘要翻译：本发明提供了人源化形式的抗EphB4小鼠单克隆抗体。本发明进一步涉及使用治疗性抗体的药物组合物，免疫治疗组合物和方法，所述治疗性抗体结合人EphB4抗原并可介导ADCC，CDC和/或细胞凋亡以治疗人恶性肿瘤和血管发生相关病症和疾病。

6. 发明申请

WO2008031056A2 HUMANIZED ANTI-CD19 ANTIBODIES AND THEIR USE IN TREATMENT OF ONCOLOGY, TRANSPLANTATION AND AUTOIMMUNE DISEASE 审中-公开
标题翻译：人源化抗CD19抗体及其在治疗肿瘤，移植和自身免疫性疾病中的应用
公开(公告)号：WO2008031056A2
公开(公告)日：2008-03-13
申请号：PCT/US2007/077916
申请日：2007-09-07
申请人： MEDIMMUNE, INC. , DAMSCHRODER, Melissa , KIENER, Peter , WU, Herren , DALL'ACQUA, William , HERBST, Ronald , COYLE, Anthony
发明人： DAMSCHRODER, Melissa , KIENER, Peter , WU, Herren , DALL'ACQUA, William , HERBST, Ronald , COYLE, Anthony
IPC分类号： A61K39/395
CPC分类号： C07K16/2803 , A61K2039/505 , C07K16/2896 , C07K16/3061 , C07K2317/24 , C07K2317/41 , C07K2317/52 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/73 , C07K2317/732 , C07K2317/77 , C07K2317/92
摘要： The present invention provides chimeric and humanized versions of anti-CD 19 mouse monoclonal antibodies. The invention further relates to pharmaceutical compositions, immunotherapeutic compositions, and methods using therapeutic antibodies that bind to the human CD 19 antigen and that may mediate ADCC, CDC, and/or apoptosis for the treatment of B cell diseases and disorders, such as, but not limited to, B cell malignancies, for the treatment and prevention of autoimmune disease, and for the treatment and prevention of graft- versus-host disease (GVHD), humoral rejection, and post-transplantation lymphoproliferative disorder in human transplant recipients.
摘要翻译：本发明提供了抗CD 19小鼠单克隆抗体的嵌合和人源化形式。本发明进一步涉及使用治疗性抗体的药物组合物，免疫治疗组合物和方法，所述治疗性抗体结合人CD 19抗原并可介导ADCC，CDC和/或细胞凋亡以治疗B细胞疾病和病症，例如但不限于不限于B细胞恶性肿瘤，用于治疗和预防自身免疫性疾病，以及用于治疗和预防人移植受体中移植物抗宿主病（GVHD），体液排斥和移植后淋巴增殖性疾病。 p>

7. 发明申请

WO2007030642A3 TOXIN CONJUGATED EPH RECEPTOR ANTIBODIES 审中-公开
标题翻译：毒素联合EPH受体抗体
公开(公告)号：WO2007030642A3
公开(公告)日：2007-10-11
申请号：PCT/US2006034894
申请日：2006-09-07
申请人： MEDIMMUNE INC , SEATTLE GENETICS INC , KINCH MICHAEL S , WU HERREN , BACHY CHRISTINE , TICE DAVID , GAO CHANGSOU , SENTER PETER D
发明人： KINCH MICHAEL S , WU HERREN , BACHY CHRISTINE , TICE DAVID , GAO CHANGSOU , SENTER PETER D
IPC分类号： C07K16/00 , A61K39/395
CPC分类号： C07K16/2866 , A61K47/6811 , A61K47/6849 , A61K2039/505 , C07K2317/24 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/75 , C07K2317/77
摘要： The present invention relates to compositions and methods for inducing cell death or stasis in cancer cells or other hyperproliferative cells using anti-EphA2 or anti-EphA4 antibodies conjugated to toxins.
摘要翻译：本发明涉及使用与毒素缀合的抗EphA2或抗EphA4抗体诱导癌细胞或其它过度增殖细胞中的细胞死亡或停滞的组合物和方法。

8. 发明申请

WO2007084253A2 HIGH AFFINITY ANTIBODIES AGAINST HMGB1 AND METHODS OF USE THEREOF 审中-公开
标题翻译： HMGB1的高亲和力抗体及其使用方法
公开(公告)号：WO2007084253A2
公开(公告)日：2007-07-26
申请号：PCT/US2006/061258
申请日：2006-11-27
申请人： MEDIMMUNE, INC. , CRITICAL THERAPEUTICS , WU, Herren , GAO, Changshou , AN, Ling-ling , KIENER, Peter , MAO, Su-yau , COYLE, Anthony , TIAN, Jane , O'KEEFE, Theresa , QIN, Shixin
发明人： WU, Herren , GAO, Changshou , AN, Ling-ling , KIENER, Peter , MAO, Su-yau , COYLE, Anthony , TIAN, Jane , O'KEEFE, Theresa , QIN, Shixin
IPC分类号： A61K39/395 , C07K16/40
CPC分类号： C07K16/24 , A61K2039/505 , C07K2317/21 , C07K2317/55 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C07K2319/32
摘要： Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn s disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.
摘要翻译：公开了用于抑制促炎细胞因子从脊椎动物细胞中释放并抑制患者炎性细胞因子级联的组合物和方法。组合物包含例如特异性结合HMG1的高亲和力抗体及其抗原性片段。本发明的高亲和力抗体和包含其的药物组合物可用于许多目的，例如作为针对广泛范围的炎性疾病和病症的治疗剂，例如败血症，类风湿性关节炎，腹膜炎，克罗恩病，再灌注损伤，败血症，内毒素性休克，囊性纤维化，心内膜炎，牛皮癣，牛皮癣关节炎，关节炎，过敏性休克，器官缺血，再灌注损伤和同种异体移植排斥。此外，本发明的高亲和力抗体可用作诊断抗体。

9. 发明申请

WO2006093496A1 PERIPLASMIC EXPRESSION OF ANTIBODIES USING A SINGLE SIGNAL SEQUENCE 审中-公开
标题翻译：使用单个信号序列的抗体的外周表达
公开(公告)号：WO2006093496A1
公开(公告)日：2006-09-08
申请号：PCT/US2005/006796
申请日：2005-03-04
申请人： MEDIMMUNE, INC. , DALL'ACQUA, William , WU, Herren , DAMSCHRODER, Melissa
发明人： DALL'ACQUA, William , WU, Herren , DAMSCHRODER, Melissa
IPC分类号： C07H21/04 , C12N15/63
CPC分类号： C07K16/2863 , C07K16/00 , C07K2317/55
摘要： The present invention relates to recombinant polynucleotides, expression vectors and methods for the production of multimeric proteins. The vectors and methods are useful for the production of multimeric protein and are unique in that they utilize a minimal number of signal sequences. More specifically, the present invention provides recombinant polynucleotide molecules and expression vectors comprising a promoter region operably linked to a transcription unit. The transcription unit is characterized by at least two DNA sequences encoding distinct polypeptides wherein at least one but not all DNA sequences further encodes a signal sequence operably linked to the DNA sequence encoding a polypeptide. The invention further provides methods of producing a multimeric protein using the expression vectors of the present invention.
摘要翻译：本发明涉及重组多核苷酸，表达载体和用于产生多聚体蛋白质的方法。载体和方法可用于生产多聚体蛋白质，并且是唯一的，因为它们利用最少量的信号序列。更具体地，本发明提供重组多核苷酸分子和包含可操作地连接到转录单位的启动子区的表达载体。转录单元的特征在于编码不同多肽的至少两个DNA序列，其中至少一个但不是全部DNA序列进一步编码与编码多肽的DNA序列可操作地连接的信号序列。本发明还提供使用本发明的表达载体产生多聚体蛋白质的方法。

10. 发明申请

WO2006023420A3 INTEGRIN ANTAGONISTS WITH ENHANCED ANTIBODY DEPENDENT CELL-MEDIATED CYTOTOXICITY ACTIVITY 审中-公开
标题翻译：具有增强抗体依赖性细胞介导的细胞毒活性的INTEGRIN拮抗剂
公开(公告)号：WO2006023420A3
公开(公告)日：2006-06-29
申请号：PCT/US2005028894
申请日：2005-08-15
申请人： MEDIMMUNE INC , WU HERREN , GAO CHANGSHOU
发明人： WU HERREN , GAO CHANGSHOU
IPC分类号： C07K16/00 , A61K39/395 , A61K39/40 , C07K1/00 , C07K14/00 , C12N15/00 , C12P21/06 , C12P21/08 , C12Q1/68
CPC分类号： G01N33/566 , C07K16/00 , C07K16/2848 , C07K16/2866 , C07K2317/52 , C07K2317/622 , C07K2317/72 , C07K2317/732 , C07K2317/92 , C07K2319/30 , G01N33/574 , G01N2500/00
摘要： The present invention relates to novel Fc variants of antibodies that immuno-specifically binds to Integrin a V ß 3 . The Fc variants comprise a variable region that immunospecifically binds to Integrin a V ß 3 and a Fc region that further comprises at least one novel amino acid residue which may provide for enhanced effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more Fc?R and/or C 1 q. Additionally, the Fc variants have altered antibody dependent cell-mediated cytotoxicity (ADCC) and/or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants of an antibody that immunospecifically binds to Integrin a V ß 3 , particularly for therapeutic purposes.
摘要翻译：本发明涉及免疫特异性结合整联蛋白3抗体的新型Fc变体。 Fc变体包含免疫特异性结合整联蛋白的可变区，以及进一步包含至少一个新的氨基酸残基的Fc区，其可以提供增强的效应子功能。更具体地，本发明提供了对一种或多种FcγR和/或C1q具有修饰的结合亲和力的Fc变体。另外，Fc变体具有改变的抗体依赖性细胞介导的细胞毒性（ADCC）和/或补体依赖性细胞毒性（CDC）活性。本发明进一步提供了用于应用所述免疫特异性结合整联蛋白的抗体的Fc变体的方法和方案，特别是出于治疗目的。

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