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    TRANSTHYRETIN VARIANTS
    3.
    发明申请
    TRANSTHYRETIN VARIANTS 审中-公开

    公开(公告)号：US20140234945A1

    公开(公告)日：2014-08-21

    申请号：US14157325

    申请日：2014-01-16

    Applicant: Amgen Inc.

    Inventor： Kenneth W. WALKER ,  Fei XIONG

    IPC: C07K14/47

    CPC classification number: C07K14/47 ,  A61K38/043 ,  A61K38/10 ,  A61K38/20 ,  A61K38/29 ,  A61K47/58 ,  A61K47/60 ,  A61K47/61 ,  A61K47/643 ,  C07K2319/31

    Abstract: The present invention provides a means for increasing the serum half-life of a selected biologically active agent by utilizing transthyretin (TTR) as a fusion partner with a biologically active agent. Specifically, the present invention provides substantially homogenous preparations of TTR (or a TTR variant)-biologically active agent fusions and PEG-TTR (PEG-TTR variant)-biologically active agent fusions. As compared to the biologically active agent alone, the TTR-biologically active agent fusion and/or PEG-TTR-biologically active agent fusion has substantially increased serum half-life.

    Abstract translation: 本发明提供了通过利用转甲状腺素蛋白（TTR）作为与生物活性剂的融合配偶体来提高选择的生物活性剂的血清半衰期的方法。 具体地说，本发明提供基本均匀的TTR（或TTR变体） - 生物活性剂融合物和PEG-TTR（PEG-TTR变体） - 生物活性剂融合物的制剂。 与单独的生物活性剂相比，TTR-生物活性剂融合和/或PEG-TTR-生物活性剂融合物具有显着增加的血清半衰期。

    MODIFIED Fc MOLECULES
    4.
    发明申请
    MODIFIED Fc MOLECULES 审中-公开
    改良的Fc分子

    公开(公告)号：US20160000932A1

    公开(公告)日：2016-01-07

    申请号：US14796502

    申请日：2015-07-10

    Applicant: AMGEN INC.

    Inventor： Colin V. GEGG ,  Kenneth W. WALKER ,  Leslie P. MIRANDA ,  Fei XIONG

    IPC: A61K47/48 ,  C07K16/00 ,  A61K38/02 ,  C07K17/00

    CPC classification number: A61K38/02 ,  A61K47/60 ,  A61K47/68 ,  A61K47/6817 ,  C07K16/00 ,  C07K17/00 ,  C07K2317/40 ,  C07K2317/52

    Abstract: Disclosed is a process for preparing a pharmacologically active compound, in which at least one internal conjugation site of an Fc domain sequence is selected that is amenable to conjugation of an additional functional moiety by a defined conjugation chemistry through the side chain of an amino acid residue at the conjugation site. An appropriate amino acid residue for conjugation may be present in a native Fc domain at the conjugation site or may be added by insertion (i.e., between amino acids in the native Fc domain) or by replacement (i.e., removing amino acids and substituting different amino acids). In the latter case, the number of amino acids added need not correspond to the number of amino acids removed from the previously existing Fc domain. This technology may be used to produce useful compositions of matter and pharmaceutical compositions containing them. A DNA encoding the inventive composition of matter, an expression vector containing the DNA, and a host cell containing the expression vector are also disclosed.

    Abstract translation: 公开了制备药理活性化合物的方法，其中选择Fc结构域序列的至少一个内部缀合位点，其适于通过定义的缀合化学通过氨基酸残基的侧链与另外的功能部分缀合 在共轭位点。 用于缀合的合适的氨基酸残基可以在缀合位点处的天然Fc结构域中存在，或者可以通过插入（即天然Fc结构域中的氨基酸之间）或替换（即，除去氨基酸并用不同的氨基 酸）。 在后一种情况下，加入的氨基酸数不需要对应于从先前存在的Fc结构域去除的氨基酸的数目。 该技术可用于生产含有它们的物质和药物组合物的有用组合物。 还公开了编码本发明组合物的DNA，含有该DNA的表达载体和含有表达载体的宿主细胞。

    COMPOSITIONS AND METHODS FOR PRODUCING BIOACTIVE FUSION PROTEINS
    5.
    发明申请
    COMPOSITIONS AND METHODS FOR PRODUCING BIOACTIVE FUSION PROTEINS 审中-公开
    用于生产活性融合蛋白的组合物和方法

    公开(公告)号：US20130209466A1

    公开(公告)日：2013-08-15

    申请号：US13861349

    申请日：2013-04-11

    Applicant: AMGEN INC.

    Inventor： Kenneth W. WALKER ,  Colin V. Gegg, JR.

    IPC: C07K16/18 ,  C07K14/435

    CPC classification number: C07K14/78 ,  A61K47/60 ,  C07K14/43504 ,  C07K14/43522 ,  C07K14/524 ,  C07K16/18 ,  C07K2319/00 ,  C07K2319/30 ,  C07K2319/31 ,  C07K2319/35

    Abstract: Disclosed is a composition of matter involving a recombinant fusion protein comprising a a pharmacologically active protein partner, and a small pharmacologically inactive protein domain partner of human origin, such as but not limited to, a 10th fibronectin III domain, a SH3 domain, a SH2 domain, a CH2 domain of IgG1, a PDZ domain, a thrombospondin repeat domain, an ubiquitin domain, a leucine-rich repeat domain, a villin headpiece HP35 domain, a villin headpiece HP76 domain, or a fragment or modification of any of these. Also disclosed are nucleic acids (e.g., DNA constructs) encoding the fusion protein, expression vectors and recombinant host cells for expression of the fusion protein, and pharmaceutical compositions containing the recombinant fusion protein and a pharmaceutically acceptable carrier, and method of producing a pharmacologically active recombinant fusion protein.

    Abstract translation: 公开了包含重组融合蛋白的组合物，其包含药理活性蛋白质配偶体和人源的小的药理学无活性蛋白质结构域伴侣，例如但不限于第10纤连蛋白III结构域，SH3结构域，SH2结构域 ，IgG1的CH2结构域，PDZ结构域，血小板反应蛋白重复结构域，泛素结构域，富含亮氨酸的重复结构域，绒毛头部HP35结构域，绒毛头部HP76结构域，或任何这些的片段或修饰。 还公开了编码融合蛋白的核酸（例如，DNA构建体），用于表达融合蛋白的表达载体和重组宿主细胞，以及含有重组融合蛋白和药学上可接受的载体的药物组合物，以及产生药理学活性的方法 重组融合蛋白。

    MODIFIED Fc MOLECULES
    6.
    发明申请
    MODIFIED Fc MOLECULES 审中-公开

    公开(公告)号：US20190151463A1

    公开(公告)日：2019-05-23

    申请号：US16206899

    申请日：2018-11-30

    Applicant: AMGEN INC.

    Inventor： Colin V. GEGG ,  Kenneth W. WALKER ,  Leslie P. MIRANDA ,  Fei XIONG

    IPC: A61K47/68 ,  C07K16/00 ,  C07K17/00 ,  A61K47/60 ,  A61K38/02

    Abstract: Disclosed is a process for preparing a pharmacologically active compound, in which at least one internal conjugation site of an Fc domain sequence is selected that is amenable to conjugation of an additional functional moiety by a defined conjugation chemistry through the side chain of an amino acid residue at the conjugation site. An appropriate amino acid residue for conjugation may be present in a native Fc domain at the conjugation site or may be added by insertion (i.e., between amino acids in the native Fc domain) or by replacement (i.e., removing amino acids and substituting different amino acids). In the latter case, the number of amino acids added need not correspond to the number of amino acids removed from the previously existing Fc domain. This technology may be used to produce useful compositions of matter and pharmaceutical compositions containing them. A DNA encoding the inventive composition of matter, an expression vector containing the DNA, and a host cell containing the expression vector are also disclosed.

    ANTI-TL1A/ANTI-TNF-ALPHA BISPECIFIC ANTIGEN BINDING PROTEINS AND USES THEREOF
    10.
    发明申请
    ANTI-TL1A/ANTI-TNF-ALPHA BISPECIFIC ANTIGEN BINDING PROTEINS AND USES THEREOF 有权

    公开(公告)号：US20220213226A1

    公开(公告)日：2022-07-07

    申请号：US17379968

    申请日：2021-07-19

    Applicant: AMGEN INC.

    Inventor： Hailing HSU ,  Gunasekaran KANNAN ,  Kenneth W. WALKER ,  Michelle HORTTER ,  Edward J. BELOUSKI

    IPC: C07K16/46 ,  C07K16/24 ,  C07K16/28 ,  A61K39/395

    Abstract: The present invention concerns antigen binding proteins that bind TL1A, including bispecific antigen binding proteins (e.g., antibodies) to TL1A and TNF-α. Such bispecific antibodies can be in a tetrameric immunoglobulin format, in which one heavy chain-light chain pair of the antibody is directed to TL1A and the other to TNF-α. The bispecific antigen binding proteins may also be comprised in an IgG-scFv fusion, in which a conventional tetrameric antibody directed to one antigen is fused to a pair of single chain Fv units directed to the other. The bispecific antigen binding protein may also be comprised in an IgG-Fab fusion, in which a Fab molecule that binds to one antigen is fused to each heavy chain of a conventional tetrameric antibody directed to the other antigen. The invention further relates to uses of the anti-TL1A binding proteins and anti-TL1A/anti-TNF-α antigen binding proteins, and pharmaceutical formulations thereof.

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