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    METHODS OF IDENTIFYING ATTRIBUTES OF THERAPEUTIC PROTEINS
    1.
    发明申请
    METHODS OF IDENTIFYING ATTRIBUTES OF THERAPEUTIC PROTEINS 审中-公开

    公开(公告)号：WO2020247790A1

    公开(公告)日：2020-12-10

    申请号：PCT/US2020/036380

    申请日：2020-06-05

    Applicant: AMGEN INC.

    Inventor： BONDARENKO, Pavel ,  CROUSE-ZEINEDDINI, Jill A. ,  KUHNS, Scott Thomas ,  NICHOLS, Andrew ,  XIAO, Gang ,  SHI, Rachel Liuqing

    IPC: G01N33/68

    Abstract: Provided herein are methods of identifying structures, e.g ., attributes, of a therapeutic protein or a target that affect an interaction between the therapeutic protein and the target. In exemplary embodiments, the method comprises: (a) applying a stress to a first sample comprising therapeutic proteins or targets; (b) contacting the first sample with a second sample comprising targets or therapeutic proteins to form a mixture comprising (i) therapeutic protein- target complexes, (ii) unbound therapeutic proteins, and (iii) unbound targets; and (c) separating the mixture into at least two fractions, wherein an unbound fraction comprises unbound therapeutic proteins or unbound targets and a bound fraction comprises therapeutic protein-target complexes; and (d) for each of the unbound fraction and bound fraction, identifying and quantifying the abundance of the structures, e.g ., attribute, present on a species of the therapeutic protein or target.

    LOW-VISCOSITY ANTIGEN BINDING PROTEINS AND METHODS OF MAKING THEM
    2.
    发明申请
    LOW-VISCOSITY ANTIGEN BINDING PROTEINS AND METHODS OF MAKING THEM 审中-公开
    低粘度抗原结合蛋白及其制备方法

    公开(公告)号：WO2018064307A2

    公开(公告)日：2018-04-05

    申请号：PCT/US2017/053967

    申请日：2017-09-28

    Applicant: AMGEN INC.

    Inventor： HUH, Joon ,  STEVENSON, Riki ,  BONDARENKO, Pavel ,  NICHOLS, Andrew ,  REN, Da ,  AGRAWAL, Neeraj Jagdish ,  SMITH, Richard

    Abstract: The present invention concerns a method for preparing antigen binding proteins with reduced viscosity. The method proceeds by replacing residues in high viscosity variable domain subfamilies with residues in correlating low viscosity subfamilies. The method further comprises substituting residues in the Fc domain with residues associated with low viscosity and adding charged residues to the C-terminus of the Fc domain. The present invention further concerns antigen binding proteins produced by this method.

    Abstract translation: 本发明涉及制备粘度降低的抗原结合蛋白的方法。 该方法通过用高粘度可变结构域亚家族中的残基替换与低粘度亚家族相关的残基来进行。 该方法进一步包括用具有低粘度的残基取代Fc结构域中的残基并将带电荷的残基添加到Fc结构域的C端。 本发明还涉及通过该方法产生的抗原结合蛋白。

    METHODS OF PROCESSING A SAMPLE FOR PEPTIDE MAPPING ANALYSIS
    7.
    发明申请
    METHODS OF PROCESSING A SAMPLE FOR PEPTIDE MAPPING ANALYSIS 审中-公开

    公开(公告)号：WO2022061092A1

    公开(公告)日：2022-03-24

    申请号：PCT/US2021/050842

    申请日：2021-09-17

    Applicant: AMGEN INC.

    Inventor： XIAO, Gang ,  BONDARENKO, Pavel ,  SHI, Liuqing ,  DILLON, Thomas M. ,  REN, Da ,  RICCI, Margaret Speed ,  CUI, Weidong ,  HARRAHY, John Joseph ,  PAWLOWSKI, Jake ,  DYKSTRA, Andrew ,  RIGGS, Dylan

    IPC: C07K14/435 ,  C12N9/76 ,  G01N33/68

    Abstract: Provided herein are methods of processing a polypeptide or protein for analysis, e.g., peptide mapping analysis by mass spectrometry. In exemplary embodiments, the method comprises incubating a digested sample at a mildly acidic pH and/or in the presence of a chaotrope, wherein the digested sample is produced by digesting a polypeptide with a protease to produce a digested sample comprising at least two peptides. In exemplary embodiments, the method comprises digesting the polypeptide with a protease which cleaves C-terminal to tryptophan to produce a digested sample comprising at least two peptides. In exemplary embodiments, the method comprises digesting the polypeptide with trypsin at an enzyme:substrate (E:S) weight ratio of about 1:1 to about 1:15 to produce a digested sample comprising at least two peptides. In exemplary aspects, the digested sample comprises at least one or two peptides each comprising a tyrosine at the C-terminus.

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