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    PERIPLASMIC EXPRESSION OF ANTIBODIES USING A SINGLE SIGNAL SEQUENCE
    2.
    发明申请
    PERIPLASMIC EXPRESSION OF ANTIBODIES USING A SINGLE SIGNAL SEQUENCE 审中-公开
    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

    Applicant: MEDIMMUNE, INC. ,  DALL'ACQUA, William ,  WU, Herren ,  DAMSCHRODER, Melissa

    Inventor： DALL'ACQUA, William ,  WU, Herren ,  DAMSCHRODER, Melissa

    IPC: C07H21/04 ,  C12N15/63

    CPC classification number: C07K16/2863 ,  C07K16/00 ,  C07K2317/55

    Abstract: 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.

    Abstract translation: 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。

    MODULATION OF ANTIBODY SPECIFICITY BY TAILORING THE AFFINITY TO COGNATE ANTIGENS
    3.
    发明申请
    MODULATION OF ANTIBODY SPECIFICITY BY TAILORING THE AFFINITY TO COGNATE ANTIGENS 审中-公开
    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

    Applicant: MEDIMMUNE, INC. ,  DALL'ACQUA, William ,  KINCH, Michael ,  CARLES-KNICH, Kelly

    Inventor： DALL'ACQUA, William ,  KINCH, Michael ,  CARLES-KNICH, Kelly

    IPC: A61K39/395 ,  C07H21/04 ,  C12P21/06 ,  C12N5/06 ,  C07K16/30

    CPC classification number: C07K16/2866 ,  C07K16/005 ,  C07K2317/21 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/92

    Abstract: 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.

    Abstract translation: 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。

    AN INTEGRATED APPROACH FOR GENERATING MULTIDOMAIN PROTEIN THERAPEUTICS
    4.
    发明申请
    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

    Applicant: MEDIMMUNE, INC. ,  ALLAN, Christian ,  WU, Herren ,  SWERS, Jeffery ,  DALL'ACQUA, William

    Inventor： ALLAN, Christian ,  WU, Herren ,  SWERS, Jeffery ,  DALL'ACQUA, William

    IPC: A61K51/10

    Abstract: 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.

    MODULATION OF ANTIBODY EFFECTOR FUNCTION BY HINGE DOMAIN ENGINEERING
    5.
    发明申请
    MODULATION OF ANTIBODY EFFECTOR FUNCTION BY HINGE DOMAIN ENGINEERING 审中-公开
    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

    Applicant: MEDIMMUNE, INC. ,  DALL'ACQUA, William ,  WU, Herren ,  DAMSCHRODER, Melissa ,  CASA-FINET, Jose

    Inventor： DALL'ACQUA, William ,  WU, Herren ,  DAMSCHRODER, Melissa ,  CASA-FINET, Jose

    IPC: C12P21/06 ,  C07K16/44

    CPC classification number: C07K16/18 ,  C07K16/00 ,  C07K16/2866 ,  C07K2317/53 ,  C07K2317/71 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/734

    Abstract: 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.

    Abstract translation: 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。

    HUMANIZATION OF ANTIBODIES
    9.
    发明申请
    HUMANIZATION OF ANTIBODIES 审中-公开
    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

    Applicant: MEDIMMUNE, INC. ,  WU, Herren ,  DALL'ACQUA, William ,  DAMSCHRODER, Melissa

    Inventor： WU, Herren ,  DALL'ACQUA, William ,  DAMSCHRODER, Melissa

    IPC: C07K16/00

    CPC classification number: C07K16/465

    Abstract: 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.

    Abstract translation: 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。

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