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    COMPOSITIONS AND METHOD FOR DEIMMUNIZATION OF PROTEINS
    3.
    发明申请
    COMPOSITIONS AND METHOD FOR DEIMMUNIZATION OF PROTEINS 审中-公开
    蛋白质去除组合物和方法

    公开(公告)号：US20120148559A1

    公开(公告)日：2012-06-14

    申请号：US13307715

    申请日：2011-11-30

    申请人： George Georgiou ,  Jason Cantor ,  Tae Hyeon Yoo

    发明人： George Georgiou ,  Jason Cantor ,  Tae Hyeon Yoo

    IPC分类号： A61K38/50 ,  C07H21/04 ,  C12N5/10 ,  C12N15/63 ,  C12Q1/68 ,  C12N9/78

    CPC分类号： C12N9/82 ,  A61K38/00 ,  C07K2319/23 ,  C07K2319/31 ,  C12Y305/01001 ,  G01N33/5023 ,  G01N2500/10

    摘要： The invention provides deimmunized mutant proteins having reduced immunogenicity while exhibiting substantially the same or greater biological activity as the proteins of interst from which they are derived, as exemplified by mutant L-asparaginase that comprises amino acid substitutions compared to wild type L-asparaginase. The invention further provides methods for screening mutant deimmunized proteins that have substantially the same or greater biological activity as a protein of interest, and methods for reducing immunogenicity, without substantially reducing biological activity, of a protein of interest.The invention's compositions and methods are useful in, for example, therapeutic applications by minimizing adverse immune responses by the host mammalian subjects to the protein of interest. Thus, the invention further provides methods for treating disease comprising administering to a subject a therapeutically effective amount of a pharmaceutical composition comprising at least one of the mutant deimmunized proteins produced by the invention's methods.

    摘要翻译： 本发明提供具有降低的免疫原性的解除免疫的突变蛋白，同时表现出与它们衍生的中间蛋白基本上相同或更大的生物学活性，如与野生型L-天冬酰胺酶相比包含氨基酸取代的突变L-天冬酰胺酶所示例。 本发明还提供了用于筛选与目的蛋白质具有基本相同或更大的生物学活性的突变体去免疫化蛋白质的方法，以及降低免疫原性而不显着降低目的蛋白质的生物学活性的方法。 本发明的组合物和方法在例如治疗应用中可用于通过使宿主哺乳动物受试者对感兴趣的蛋白质的不良免疫应答最小化。 因此，本发明还提供了治疗疾病的方法，包括向受试者施用治疗有效量的药物组合物，其包含本发明方法产生的至少一种突变型去免疫化蛋白质。

    Gateway-based system and method for tandem free operation
    4.
    发明授权
    Gateway-based system and method for tandem free operation 有权
    基于网关的系统和方法，用于串联自由操作

    公开(公告)号：US08059663B1

    公开(公告)日：2011-11-15

    申请号：US10616679

    申请日：2003-07-10

    申请人： Manish Mangal ,  George Georgiou ,  Anand Chakraborty

    发明人： Manish Mangal ,  George Georgiou ,  Anand Chakraborty

    IPC分类号： H04L12/28 ,  H04L12/56

    CPC分类号： H04W36/0033 ,  H04W28/06 ,  H04W76/10 ,  H04W88/16

    摘要： Mobile switching centers (MSCs) in serving systems are interconnected by gateways for tandem free operation. The serving systems route calls involving two mobile stations that use the same compressed digital format through the gateways. The gateways carry the media exchanged during the call in the compressed digital format in order to avoid tandem transcoding. When a serving system hands off a mobile station involved in a tandem free call, the call pathway is extended through the gateways so that the call remains tandem free.

    摘要翻译： 服务系统中的移动交换中心（MSC）通过网关互连，实现串联自由运行。 服务系统通过网关路由涉及使用相同压缩数字格式的两个移动台的呼叫。 网关在呼叫期间以压缩数字格式携带媒体交换，以避免串联转码。 当服务系统切断涉及无线电通话的移动台时，呼叫路径通过网关延伸，使得呼叫保持串通。

    IMMUNOGLOBULIN FC POLYPEPTIDES
    6.
    发明申请
    IMMUNOGLOBULIN FC POLYPEPTIDES 有权
    多柔比星FC多糖

    公开(公告)号：US20100330076A1

    公开(公告)日：2010-12-30

    申请号：US12827386

    申请日：2010-06-30

    申请人： George Georgiou ,  Sang Taek Jung ,  Sai Reddy

    发明人： George Georgiou ,  Sang Taek Jung ,  Sai Reddy

    IPC分类号： A61K39/395 ,  C07K16/42 ,  C07H21/04 ,  C12N5/10 ,  C12P21/00 ,  C12N5/071 ,  G01N33/53 ,  A61P37/04

    CPC分类号： G01N33/56911 ,  C07K16/00 ,  C07K16/005 ,  C07K16/32 ,  C07K2317/24 ,  C07K2317/41 ,  C07K2317/72 ,  C07K2317/732 ,  C07K2317/75 ,  C07K2317/76 ,  G01N33/6857 ,  G01N2500/10

    摘要： Methods and compositions involving polypeptides having an aglycosylated antibody Fc domain. In certain embodiments, polypeptides have an aglycosylated Fc domain that contains one or more substitutions compared to a native Fc domain. Additionally, some embodiments involve an Fc domain that is binds some Fc receptors but not others. For example, polypeptides are provided with an aglycosylated Fe domain that selectively binds FcγRI at a level within 2-fold of a glycosylated Fc domain, but that is significantly reduced for binding to other Fc receptors. Furthermore, methods and compositions are provided for promoting antibody-dependent cell-mediated toxicity (ADCC) using a polypeptide having a modified aglycosylated Fc domain and a second non-Fc binding domain, which can be an antigen binding region of an antibody or a non-antigen binding region. Some embodiments concern antibodies with such polypeptides, which may have the same or different non-Fc binding domain.

    摘要翻译： 涉及具有糖基化抗体Fc结构域的多肽的方法和组合物。 在某些实施方案中，多肽具有与天然Fc结构域相比含有一个或多个取代的糖基化Fc结构域。 另外，一些实施方案涉及结合一些Fc受体而不是其它Fc受体的Fc结构域。 例如，提供多肽具有糖基化的Fe结构域，其选择性地结合FcγRI在糖基化Fc结构域的2倍以内的水平，但是与其它Fc受体结合显着降低。 此外，提供了使用具有修饰的糖苷基化Fc结构域和第二非Fc结合结构域的多肽来促进抗体依赖性细胞介导的毒性（ADCC）的方法和组合物，其可以是抗体或非抗体的抗原结合区域 - 抗原结合区。 一些实施方案涉及具有这样的多肽的抗体，其可以具有相同或不同的非Fc结合结构域。

    Prokaryotic host cells for expressing proteins rich in disulfide bonds
    7.
    发明授权
    Prokaryotic host cells for expressing proteins rich in disulfide bonds 有权
    用于表达富含二硫键的蛋白质的原核宿主细胞

    公开(公告)号：US07816117B2

    公开(公告)日：2010-10-19

    申请号：US11411988

    申请日：2006-04-26

    申请人： Jonathan Beckwith ,  Daniel Ritz ,  Melinda Faulkner ,  Stephanie Gon ,  George Georgiou

    发明人： Jonathan Beckwith ,  Daniel Ritz ,  Melinda Faulkner ,  Stephanie Gon ,  George Georgiou

    IPC分类号： C12N1/12 ,  C12N9/02 ,  C12P21/04

    CPC分类号： C12N9/0065 ,  C12N2500/44 ,  C12N2501/70 ,  C12N2510/02

    摘要： The invention provides composition and methods for producing proteins of interest which comprise at least one disulfide bond, include proteins which in their mature form do not contain disulfide bonds, but whose precursor molecule contained at least one disulfide bond. The methods employ a host cell modified to more efficiently produce properly folded disulfide bond containing proteins. The host cells generally contain a mutation in one or more reductase genes, and can be further genetically modified to increase their growth rate, and are further optionally modified to increase the expression of a catalyst of disulfide bond formation. Host cells, methods for u sing such to produce proteins of interest, proteins of interest produced by these methods are within the scope of the invention.

    摘要翻译： 本发明提供用于产生包含至少一个二硫键的感兴趣蛋白质的组合物和方法，包括其成熟形式不含二硫键但其前体分子含有至少一个二硫键的蛋白质。 该方法使用修饰的宿主细胞以更有效地产生适当折叠的含二硫键的蛋白质。 宿主细胞通常在一个或多个还原酶基因中含有突变，并且可进行进一步遗传修饰以增加其生长速率，并进一步任选地修饰以增加二硫键形成催化剂的表达。 宿主细胞，用于产生感兴趣的蛋白质的方法，通过这些方法生产的感兴趣的蛋白质在本发明的范围内。

    ISOLATION OF BINDING PROTEINS WITH HIGH AFFINITY TO LIGANDS
    8.
    发明申请
    ISOLATION OF BINDING PROTEINS WITH HIGH AFFINITY TO LIGANDS 有权
    分离具有高亲和力的结合蛋白

    公开(公告)号：US20070065913A1

    公开(公告)日：2007-03-22

    申请号：US11461757

    申请日：2006-08-01

    申请人： Gang Chen ,  Andrew Hayhurst ,  Jeffrey Thomas ,  Brent Iverson ,  George Georgiou

    发明人： Gang Chen ,  Andrew Hayhurst ,  Jeffrey Thomas ,  Brent Iverson ,  George Georgiou

    IPC分类号： C12P21/06 ,  C07H21/04 ,  C12N9/00 ,  C12N1/21 ,  C07K14/195 ,  C12N15/74

    CPC分类号： C12N15/1034

    摘要： The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides via “display-less” library screening. In the technique, libraries of candidate binding proteins, such as antibody sequences, are expressed in soluble form in the periplasmic space of gram negative bacteria, such as Escherichia coli, and are mixed with a labeled ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the concentration of the labeled ligand bound to the binding protein is increased and allows the cells to be isolated from the rest of the library. Where fluorescent labeling of the target ligand is used, cells may be isolated by fluorescence activated cell sorting (FACS). The approach is more rapid than prior art methods and avoids problems associated with the surface-expression of ligand fusion proteins employed with phage display.

    摘要翻译： 本发明通过提供通过“无显示”文库筛选分离能够结合小分子和肽的结合蛋白的快速方法来克服现有技术的缺陷。 在该技术中，候选结合蛋白（例如抗体序列）的文库以可溶形式表达在革兰氏阴性细菌如大肠杆菌的周质空间中，并与标记的配体混合。 在表达对配体具有亲和性的重组多肽的克隆中，与结合蛋白结合的标记配体的浓度增加，并允许细胞与文库的其余部分分离。 当使用靶配体的荧光标记时，可以通过荧光激活细胞分选（FACS）分离细胞。 该方法比现有技术方法更快速，并避免与噬菌体展示所用配体融合蛋白的表面表达相关的问题。

    Isolation of binding proteins with high affinity to ligands
    9.
    发明授权
    Isolation of binding proteins with high affinity to ligands 有权
    结合蛋白与配体的高亲和力分离

    公开(公告)号：US07083945B1

    公开(公告)日：2006-08-01

    申请号：US09699023

    申请日：2000-10-27

    申请人： Gang Chen ,  Andrew Hayhurst ,  Jeffrey G. Thomas ,  Brent L. Iverson ,  George Georgiou

    发明人： Gang Chen ,  Andrew Hayhurst ,  Jeffrey G. Thomas ,  Brent L. Iverson ,  George Georgiou

    IPC分类号： C12P21/06 ,  C12P21/04 ,  C12N15/09 ,  G01N33/53

    CPC分类号： C12N15/1034

    摘要： The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides via “display-less” library screening. In the technique, libraries of candidate binding proteins, such as antibody sequences, are expressed in soluble form in the periplasmic space of gram negative bacteria, such as Escherichia coli, and are mixed with a labeled ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the concentration of the labeled ligand bound to the binding protein is increased and allows the cells to be isolated from the rest of the library. Where fluorescent labeling of the target ligand is used, cells may be isolated by fluorescence activated cell sorting (FACS). The approach is more rapid than prior art methods and avoids problems associated with the surface-expression of ligand fusion proteins employed with phage display.

    摘要翻译： 本发明通过提供通过“无显示”文库筛选分离能够结合小分子和肽的结合蛋白的快速方法来克服现有技术的缺陷。 在该技术中，候选结合蛋白（例如抗体序列）的文库以可溶形式表达在革兰氏阴性细菌如大肠杆菌的周质空间中，并与标记的配体混合。 在表达对配体具有亲和性的重组多肽的克隆中，与结合蛋白结合的标记配体的浓度增加，并允许细胞与文库的其余部分分离。 当使用靶配体的荧光标记时，可以通过荧光激活细胞分选（FACS）分离细胞。 该方法比现有技术方法更快速，并避免与噬菌体展示所用配体融合蛋白的表面表达相关的问题。