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1. 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>

2. 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。

3. 发明申请

WO2006047639A2 MODULATION OF ANTIBODY SPECIFICITY BY TAILORING THE AFFINITY TO COGNATE ANTIGENS 审中-公开
标题翻译：通过将亲和力调整为抗原抗体来调节抗体特异性
公开(公告)号：WO2006047639A2
公开(公告)日：2006-05-04
申请号：PCT/US2005/038668
申请日：2005-10-27
申请人： MEDIMMUNE, INC. , DALL'ACQUA, William , KINCH, Michael , CARLES-KNICH, Kelly
发明人： DALL'ACQUA, William , KINCH, Michael , CARLES-KNICH, Kelly
IPC分类号： A61K39/395 , C07H21/04 , C12P21/06 , C12N5/06 , C07K16/30
CPC分类号： C07K16/2866 , C07K16/005 , C07K2317/21 , C07K2317/55 , C07K2317/565 , C07K2317/92
摘要： The present invention relates to methods and compositions designed for the treatment, management, prevention and/o amelioration of various disorders associated with aberrant expression and/or activity of one or more Eph receptor tyrosine kinase family members and/or one or more Eph receptor ligands, particularly the Ephrins. In particular, the invention provides methods for the treatment, management , prevention and/or amelioration of a disorder associated with aberrant expression and/or activity(ies) of one or more Eph receptors and/or one or more Ephrins, the method comprising administering to a subject in need thereof an effective amount of one or more Eph/Ephrin Modulators. The present invention further relates to methods of modulating antibody specificity by tailoring the affinity to cognate antigens.
摘要翻译：本发明涉及设计用于治疗，管理，预防和/或改善与一种或多种Eph受体酪氨酸激酶家族成员和/或一种或多种Eph受体配体的异常表达和/或活性相关的各种疾病的方法和组合物，特别是Ephrins。特别地，本发明提供了治疗，管理，预防和/或改善与一种或多种Eph受体和/或一种或多种Ephrins的异常表达和/或活性相关的病症的方法，所述方法包括施用对有需要的受试者有效量的一种或多种Eph / Ephrin调节剂。本发明还涉及通过调整对同源抗原的亲和力来调节抗体特异性的方法。

4. 发明申请

WO2007005612A3 AN INTEGRATED APPROACH FOR GENERATING MULTIDOMAIN PROTEIN THERAPEUTICS 审中-公开
公开(公告)号：WO2007005612A3
公开(公告)日：2007-01-11
申请号：PCT/US2006/025590
申请日：2006-06-30
申请人： MEDIMMUNE, INC. , ALLAN, Christian , WU, Herren , SWERS, Jeffery , DALL'ACQUA, William
发明人： ALLAN, Christian , WU, Herren , SWERS, Jeffery , DALL'ACQUA, William
IPC分类号： A61K51/10
摘要： The invention provides method for therapeutic protein drug development that incorporates therapeutic and/or formulation and/or manufacturing considerations in the early screening process. The approach involves screening a plurality of different variants of a domain that have been determined to have the desired therapeutic property to identify one or more variants that have desired therapeutic and/or formulation characteristics, and constructing the full multidomain proteins using the identified domain variants. The present invention also provides a method for determining the shelf life of multidomain proteins in formulations. The method comprises determining a thermal denaturation and/or renaturation curve of a domain of the protein whose unfolding leads to aggregation of the protein in a solution. The method evaluates the shelf life of the multidomain protein based on the denaturation/renaturation curve. The invention also provides methods for engineering multidomain proteins to improve their therapeutic and/or formulation characteristics.

5. 发明申请

WO2006116260A2 MODULATION OF ANTIBODY EFFECTOR FUNCTION BY HINGE DOMAIN ENGINEERING 审中-公开
标题翻译：通过兴奋剂工程调整抗体效应函数
公开(公告)号：WO2006116260A2
公开(公告)日：2006-11-02
申请号：PCT/US2006/015393
申请日：2006-04-25
申请人： MEDIMMUNE, INC. , DALL'ACQUA, William , WU, Herren , DAMSCHRODER, Melissa , CASA-FINET, Jose
发明人： DALL'ACQUA, William , WU, Herren , DAMSCHRODER, Melissa , CASA-FINET, Jose
IPC分类号： C12P21/06 , C07K16/44
CPC分类号： C07K16/18 , C07K16/00 , C07K16/2866 , C07K2317/53 , C07K2317/71 , C07K2317/72 , C07K2317/732 , C07K2317/734
摘要： The present invention relates to novel molecules (Fc variants) comprising at least one antigen binding region and an Fc region that further comprises a modified hinge which alters the binding of Fc to one or more Fc ligand (e.g., FcγRs) and/or modulates effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more FcγR and/or CIq. 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 particularly for therapeutic purposes.
摘要翻译：本发明涉及包含至少一个抗原结合区和Fc区的新分子（Fc变体），其还包含修饰的铰链，其改变Fc与一个或多个Fc配体（例如FcγR）的结合和/或调节效应子功能。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。本发明还提供了用于所述Fc变体的应用的方法和方案，特别是用于治疗目的。

6. 发明申请

WO2010141329A1 MOLECULES WITH EXTENDED HALF-LIVES AND USES THEREOF 审中-公开
标题翻译：具有扩展性半衰期的分子及其用途
公开(公告)号：WO2010141329A1
公开(公告)日：2010-12-09
申请号：PCT/US2010/036497
申请日：2010-05-28
申请人： MEDIMMUNE, LLC , LUBMAN, Olga , DALL'ACQUA, William , WU, Herren
发明人： LUBMAN, Olga , DALL'ACQUA, William , WU, Herren
IPC分类号： A61K38/00
CPC分类号： A61K47/48538 , A61K39/3955 , A61K47/62 , A61K47/6835 , A61K2039/505 , C07K14/315 , C07K16/18 , C07K2317/52 , C07K2317/94 , C07K2319/21 , C07K2319/30 , C07K2319/31 , C07K2319/41
摘要： The invention is directed to a molecule comprising an albumin binding domain (ABD) and an FcRn binding moiety, wherein said molecule has enhanced pharmacologic properties in vivo .
摘要翻译：本发明涉及包含白蛋白结合结构域（ABD）和FcRn结合部分的分子，其中所述分子在体内具有增强的药理学性质。

7. 发明申请

WO2010088444A1 HUMAN ANTI-IL-6 ANTIBODIES WITH EXTENDED IN VIVO HALF-LIFE AND THEIR USE IN TREATMENT OF ONCOLOGY, AUTOIMMUNE DISEASES AND INFLAMMATORY DISEASES 审中-公开
标题翻译：人类抗IL-6抗体在体细胞生存中的应用及其在治疗肿瘤，自身免疫性疾病和炎症疾病中的应用
公开(公告)号：WO2010088444A1
公开(公告)日：2010-08-05
申请号：PCT/US2010/022478
申请日：2010-01-29
申请人： MEDIMMUNE, LLC , BOWEN, Michael , WU, Herren , DALL'ACQUA, William , KIENER, Peter , JALLAL, Bahija , COYLE, Anthony
发明人： BOWEN, Michael , WU, Herren , DALL'ACQUA, William , KIENER, Peter , JALLAL, Bahija , COYLE, Anthony
IPC分类号： A61K39/395 , C07K16/24
CPC分类号： C07K16/248 , A61K39/3955 , A61K45/06 , A61K2039/505 , C07K2317/21 , C07K2317/52 , C07K2317/56 , C07K2317/622 , C07K2317/72 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C07K2317/94
摘要： The present invention provides human anti-IL-6 antibodies with extended in vivo half-life. The invention further relates to pharmaceutical compositions, therapeutic compositions, and methods using therapeutic antibodies that bind to IL-6 and that has an extended in vivo half-life for the treatment and prevention of IL-6 mediated diseases and disorders, such as, but not limited to, inflammatory diseases and disorders, autoimmune diseases and disorders and tumors.
摘要翻译：本发明提供具有延长体内半衰期的人抗IL-6抗体。本发明进一步涉及药物组合物，治疗组合物和使用结合IL-6的治疗性抗体并且具有延长的体内半衰期以用于治疗和预防IL-6介导的疾病和病症的方法，例如但是不限于炎性疾病和病症，自身免疫性疾病和病症和肿瘤。

8. 发明申请

WO2006004663A2 INCREASING THE PRODUCTION OF RECOMBINANT ANTIBODIES IN MAMMALIAN CELLS BY SITE-DIRECTED MUTAGENESIS 审中-公开
标题翻译：通过现场指导的MUTAGENESIS增加妈妈细胞中重组抗体的产生
公开(公告)号：WO2006004663A2
公开(公告)日：2006-01-12
申请号：PCT/US2005/022738
申请日：2005-06-24
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 , C12P21/06 , C12N5/06 , C07K16/44
CPC分类号： C07K16/2866 , C07K16/00 , C07K16/2848 , C07K2317/24 , C07K2317/565 , C07K2317/567 , C07K2317/92 , C12N2510/02
摘要： The present invention relates to a reliable, reproducible method for improving the producibility of an antibody. More specifically, this invention provides a method for modifying the heavy chain of an antibody to improve its producibility in eukaryotic cells. Additionally, the method of the invention may improve both antibody producibility and one or more antigen binding characteristics. The invention further provides modified antibodies which are better produced and which have either no change in their antigen binding characteristics or exhibit improved antigen binding characteristics.
摘要翻译：本发明涉及提高抗体可生产性的可靠，可重现的方法。更具体地，本发明提供了修饰抗体重链以改善其在真核细胞中的可生产性的方法。此外，本发明的方法可以改善抗体可产生性和一种或多种抗原结合特征。本发明还提供了更好地产生并且其抗原结合特征没有变化或表现出改善的抗原结合特征的修饰抗体。

9. 发明申请

WO2005035575A2 HUMANIZATION OF ANTIBODIES 审中-公开
标题翻译：抗体人类化
公开(公告)号：WO2005035575A2
公开(公告)日：2005-04-21
申请号：PCT/US2004/027188
申请日：2004-08-20
申请人： MEDIMMUNE, INC. , WU, Herren , DALL'ACQUA, William , DAMSCHRODER, Melissa
发明人： WU, Herren , DALL'ACQUA, William , DAMSCHRODER, Melissa
IPC分类号： C07K16/00
CPC分类号： C07K16/465
摘要： The present invention provides methods of re-engineering or re-shaping an antibody from a first species, wherein the re-engineered or re-shaped antibody does not elicit undesired immune response in a second species, and the re-engineered or re-shaped antibody retains substantially the same antigen binding-ability of the antibody from the first species. In accordance with the present invention, a combinatorial library comprising the CDRs of the antibody from the first species fused in frame with framework regions derived from a second species can be constructed and screened for the desired modified antibody. In particular, the present invention provides methods utilizing low homology acceptor antibody frameworks for efficiently humanizing an antibody or a fragment thereof. The present invention also provides antibodies produced by the methods of the invention.
摘要翻译：本发明提供了重新设计或重新形成来自第一种类的抗体的方法，其中重新设计或重新形成的抗体在第二种物种中不引发不期望的免疫应答，并且重新设计或重新形成抗体保留了来自第一物种的抗体基本相同的抗原结合能力。根据本发明，可以构建包含来自与来自第二种类的框架区域框架融合的第一物种的抗体的CDR的组合文库，并筛选所需的修饰抗体。特别地，本发明提供利用低同源受体抗体框架有效地使抗体或其片段人源化的方法。本发明还提供通过本发明的方法制备的抗体。

10. 发明申请

WO2009009103A3 CRYSTALS AND STRUCTURE OF HUMAN IgG Fc VARIANT 审中-公开
公开(公告)号：WO2009009103A3
公开(公告)日：2009-01-15
申请号：PCT/US2008/008482
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： C12P21/08
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 FcγR.

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