利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

22 条记录 (耗时 0.028 秒)

    Proteins with integrin-like activity
    1.
    发明授权
    Proteins with integrin-like activity 失效

    公开(公告)号：US06951927B2

    公开(公告)日：2005-10-04

    申请号：US09902481

    申请日：2001-07-09

    申请人： Stephen Mayo ,  Julia Shifman ,  Motomu Shimaoka ,  Timothy Springer

    发明人： Stephen Mayo ,  Julia Shifman ,  Motomu Shimaoka ,  Timothy Springer

    IPC分类号： A61K38/00 ,  C07K14/705 ,  C07K1/107

    CPC分类号： C07K14/70546 ,  A61K38/00

    摘要： The invention relates to novel proteins with novel integrin and I domain activity and nucleic acids encoding these proteins. The invention further relates to the use of the novel proteins in the treatment of integrin related disorders. TABLE 1 Computationally designed mutantsa WTido1qido1rido2rjlm2r BackboneEnergyb 1ido−1037 −1145−1138−1116 −678 1jlm−1059+82758 −840−1000−1086 PositionResidues 139I——V— 153M——A— 156FLW—— 157V——I— 160VI——— 199VIII— 215ILL—V 219V———I 223F———L 238VFFII 239VLLL— 240ILL—— 259ALL—— 269IL——— 271VF——— 287IVVV— 299VAII— 308IV——— aMutants are named according to the structure that was stabilized (ido or jlm), the solvation potential used (1 or 2) and the definition of core residues (q or r). bThe lowest energy rotamer configuration was calculated for each sequence in the lido structure, and cross-calculated in the ljlm structure, using both solvent potentials; all 50 core residues were used in order to make the q and r energies comparable. Results are shown for solvent potential 1 and were similar for potential 2. # A severe clash of the side-chain of F271 with the backbone caused the high energy of the 1q sequence in the 1jlm structure; no movement of the backbone is allowed by the design method.

    Modified polypeptides stabilized in a desired conformation and methods for producing same
    4.
    发明授权
    Modified polypeptides stabilized in a desired conformation and methods for producing same 有权
    以所需构象稳定的修饰多肽及其制备方法

    公开(公告)号：US07241869B2

    公开(公告)日：2007-07-10

    申请号：US11080026

    申请日：2005-03-15

    申请人： Timothy A. Springer ,  Motomu Shimaoka ,  Chafen Lu

    发明人： Timothy A. Springer ,  Motomu Shimaoka ,  Chafen Lu

    IPC分类号： C07K14/705 ,  C07K1/107

    CPC分类号： C07K14/70546 ,  A61K38/00 ,  Y10S930/26

    摘要： The present invention provides a method for stabilizing a protein in a desired conformation by introducing at least one disulfide bond into the polypeptide. Computational design is used to identify positions where cysteine residues can be introduced to form a disulfide bond in only one protein conformation, and therefore lock the protein in a given conformation. Accordingly, antibody and small molecule therapeutics are selected that are specific for the desired protein conformation.The invention also provides modified integrin I-domain polypeptides that are stabilized in a desired conformation. The invention further provides screening assays and therapeutic methods utilizing the modified integrin I-domains of the invention.

    摘要翻译： 本发明提供了通过在多肽中引入至少一个二硫键来稳定所需构象的蛋白质的方法。 计算设计用于鉴定可以引入半胱氨酸残基以仅在一个蛋白质构象中形成二硫键的位置，因此将蛋白质锁定在给定的构象中。 因此，选择对所需蛋白质构象具有特异性的抗体和小分子治疗剂。 本发明还提供以所需构象稳定的修饰的整联蛋白I结构域多肽。 本发明还提供了利用本发明的修饰的整联蛋白I结构域的筛选测定和治疗方法。

    Modified polypeptides stabilized in a desired conformation and methods for producing same
    6.
    发明授权
    Modified polypeptides stabilized in a desired conformation and methods for producing same 有权
    以所需构象稳定的修饰多肽及其制备方法

    公开(公告)号：US07879577B2

    公开(公告)日：2011-02-01

    申请号：US12592275

    申请日：2009-11-20

    申请人： Timothy A. Springer ,  Motomu Shimaoka ,  Chafen Lu

    发明人： Timothy A. Springer ,  Motomu Shimaoka ,  Chafen Lu

    IPC分类号： C12P21/06 ,  C12P11/00 ,  A61K38/00 ,  A61K31/67

    CPC分类号： C07K14/70546 ,  A61K38/00 ,  Y10S930/26

    摘要： The present invention provides a method for stabilizing a protein in a desired conformation by introducing at least one disulfide bond into the polypeptide. Computational design is used to identify positions where cysteine residues can be introduced to form a disulfide bond in only one protein conformation, and therefore lock the protein in a given conformation. Accordingly, antibody and small molecule therapeutics are selected that are specific for the desired conformation. The invention also provides modified integrin I-domain polypeptides that are stabilized in a desired conformation. The invention further provides screening assays and therapeutic methods utilizing the modified integrin I-domains of the invention.

    摘要翻译： 本发明提供了通过在多肽中引入至少一个二硫键来稳定所需构象的蛋白质的方法。 计算设计用于鉴定可以引入半胱氨酸残基以仅在一个蛋白质构象中形成二硫键的位置，因此将蛋白质锁定在给定的构象中。 因此，选择对所需构象特异的抗体和小分子治疗剂。 本发明还提供以所需构象稳定的修饰的整联蛋白I结构域多肽。 本发明还提供了利用本发明的修饰的整联蛋白I结构域的筛选测定和治疗方法。

    TREATMENT OR PREVENTION OF INFLAMMATION BY TARGETING CYCLIN D1
    7.
    发明申请
    TREATMENT OR PREVENTION OF INFLAMMATION BY TARGETING CYCLIN D1 审中-公开
    通过定期循环D1治疗或预防炎症

    公开(公告)号：US20100285002A1

    公开(公告)日：2010-11-11

    申请号：US12811229

    申请日：2008-12-30

    申请人： Dan Peer ,  Motomu Shimaoka

    发明人： Dan Peer ,  Motomu Shimaoka

    IPC分类号： A61K39/395 ,  A61K31/7088 ,  A61P37/00 ,  A61P29/00 ,  A61P25/28 ,  A61P19/02

    CPC分类号： C12N15/113 ,  C12N2310/14

    摘要： In one aspect, the invention relates to the treatment and/or prevention of inflammation by inhibition of cyclin D1. In one embodiment, Th1-mediated inflammation is selectively inhibited or reduced by a method comprising administering an agent that inhibits cyclin D1. In another embodiment, an autoimmune disease or a disorder characterized by or involving a Th1 inflammatory response is treated or prevented in a subject by a method comprising administering to the subject an agent that inhibits cyclin D1.

    摘要翻译： 一方面，本发明涉及通过抑制细胞周期蛋白D1治疗和/或预防炎症。 在一个实施方案中，通过包括施用抑制细胞周期蛋白D1的试剂的方法选择性地抑制或减少Th1介导的炎症。 在另一个实施方案中，通过包括向受试者施用抑制细胞周期蛋白D1的药物的方法，在受试者中治疗或预防特征为或涉及Th1炎症反应的自身免疫疾病或病症。

    Modified polypeptides stabilized in a desired conformation and methods for producing same
    8.
    发明授权
    Modified polypeptides stabilized in a desired conformation and methods for producing same 有权
    以所需构象稳定的修饰多肽及其制备方法

    公开(公告)号：US07160541B2

    公开(公告)日：2007-01-09

    申请号：US09945265

    申请日：2001-08-31

    申请人： Timothy A. Springer ,  Motomu Shimaoka ,  Chafen Lu

    发明人： Timothy A. Springer ,  Motomu Shimaoka ,  Chafen Lu

    IPC分类号： A61K39/395 ,  C07K16/46 ,  C07K16/28 ,  C07K16/00

    CPC分类号： C07K14/70546 ,  A61K38/00 ,  Y10S930/26

    摘要： The present invention provides a method for stabilizing a protein in a desired conformation by introducing at least one disulfide bond into the polypeptide. Computational design is used to identify positions where cysteine residues can be introduced to form a disulfide bond in only one protein conformation, and therefore lock the protein in a given conformation. Accordingly, antibody and small molecule therapeutics are selected that are specific for the desired protein conformation. Modified integrin I-domain polypeptides that are stabilized in a desired conformation are also provided. Finally, screening assays and therapeutic methods utilizing the modified integrin I-domains of the invention are also provided.

    摘要翻译： 本发明提供了通过在多肽中引入至少一个二硫键来稳定所需构象的蛋白质的方法。 计算设计用于鉴定可以引入半胱氨酸残基以仅在一个蛋白质构象中形成二硫键的位置，因此将蛋白质锁定在给定的构象中。 因此，选择对所需蛋白质构象具有特异性的抗体和小分子治疗剂。 还提供了以所需构象稳定的修饰的整联蛋白I结构域多肽。 最后，还提供了使用本发明的修饰的整联蛋白I结构域的筛选测定和治疗方法。

    TARGETED DELIVERY TO LEUKOCYTES USING PROTEIN CARRIERS
    9.
    发明申请
    TARGETED DELIVERY TO LEUKOCYTES USING PROTEIN CARRIERS 审中-公开
    使用蛋白质载体的目标交付给LEUKOCYTES

    公开(公告)号：US20130129752A1

    公开(公告)日：2013-05-23

    申请号：US12298361

    申请日：2007-04-25

    申请人： Dan Peer ,  Motomu Shimaoka ,  Judy Lieberman

    发明人： Dan Peer ,  Motomu Shimaoka ,  Judy Lieberman

    IPC分类号： A61K39/395 ,  C12N5/06 ,  A61K35/12 ,  C07K16/18

    CPC分类号： C12N15/87 ,  A61K2039/55555 ,  C12N15/111 ,  C12N15/1138 ,  C12N2310/14 ,  C12N2320/32

    摘要： Disclosed herein are is a leukocyte-selective delivery agent comprising, a targeting moiety that selectively binds LFA-I, a protein carrier moiety covalently linked to the targeting moiety, and a therapeutic agent associated with the carrier moiety. The delivery agent may be further selective for activated leukocytes, wherein the targeting moiety selectively binds LFA-I in its activated conformation. The targeting moiety comprises an antibody or functional fragment thereof, such as an scFV. Examples of antibodies or fragments thereof which selectively bind LFA-I activated conformation bind to the locked open I domain of LFA-I, or binds to the leg domain of the β2 subunit of LFA-I ((ILP2)—The antibody or functional fragment thereof may alternatively bind non-selectively to both low affinity and high affinity LFA-I. Examples of a non-protein carrier are a basic polypeptide such as protamine or a functional fragment thereof. One such fragment is RSQSRSRYYRQRQRSRRRRRRS. The therapeutic agent may comprise one or more of a nucleic acid, a small molecule, a polypeptide, and an antibody or functional fragment thereof. An example of a nucleic acid delivery agent comprises an RNA interference molecule. Examples of RNA interference molecules are siRNA, dsRNA, StRNA, shRNA, miRNA, and combinations thereof. Specific siRNAs are provided. Other examples of a nucleic acid delivery agent are a small RNA, an antagomir, an LNA, and an antisense oligonucleotide. Methods for leukocyte-selective delivery, or activated leukocyte-selective delivery in vivo, in vitro and ex vivo are also provided.

    摘要翻译： 本文公开的是白细胞选择性递送剂，其包含选择性结合LFA-1的靶向部分，与靶向部分共价连接的蛋白质载体部分和与载体部分相关联的治疗剂。 递送剂可以对活化的白细胞进一步选择性，其中靶向部分选择性地结合其活化构象中的LFA-1。 靶向部分包含抗体或其功能片段，例如scFV。 选择性结合LFA-1激活的构象的抗体或其片段的实例与LFA-1的锁定的开放I结构域结合，或与LFA-1（（ILP2））的β2亚基的腿结构域结合 - 抗体或功能片段 非蛋白质载体的实例可以是碱性多肽，例如鱼精蛋白或其功能片段，一个这样的片段是RSQSRSRYYRQRQRSRRRRRRS，治疗剂可以包含一种 核酸分子的实例包括RNA干扰分子，RNA干扰分子的实例是siRNA，dsRNA，StRNA，shRNA， miRNA及其组合提供特异性siRNA，核酸递送剂的其它实例是小RNA，antagomir，LNA和反义寡核苷酸。白细胞选择方法 还提供体外和离体的活性递送或活化的白细胞选择性递送。

    Modified polypeptides stabilized in a desired conformation and methods for producing same
    10.
    发明授权
    Modified polypeptides stabilized in a desired conformation and methods for producing same 有权
    以所需构象稳定的修饰多肽及其制备方法

    公开(公告)号：US07968284B2

    公开(公告)日：2011-06-28

    申请号：US12964813

    申请日：2010-12-10

    申请人： Timothy A. Springer ,  Motomu Shimaoka ,  Chafen Lu

    发明人： Timothy A. Springer ,  Motomu Shimaoka ,  Chafen Lu

    IPC分类号： C12Q1/00 ,  G01N33/53

    CPC分类号： C07K14/70546 ,  A61K38/00 ,  Y10S930/26

    摘要： The present invention provides a method for stabilizing a protein in a desired conformation by introducing at least one disulfide bond into the polypeptide. Computational design is used to identify positions where cysteine residues can be introduced to form a disulfide bond in only one protein conformation, and therefore lock the protein in a given conformation. Accordingly, antibody and small molecule therapeutics are selected that are specific for the desired protein conformation. The invention also provides modified integrin I-domain polypeptides that are stabilized in a desired conformation. The invention further provides screening assays and therapeutic methods utilizing the modified integrin I-domains of the invention.

    摘要翻译： 本发明提供了通过在多肽中引入至少一个二硫键来稳定所需构象的蛋白质的方法。 计算设计用于鉴定可以引入半胱氨酸残基以仅在一个蛋白质构象中形成二硫键的位置，因此将蛋白质锁定在给定的构象中。 因此，选择对所需蛋白质构象具有特异性的抗体和小分子治疗剂。 本发明还提供以所需构象稳定的修饰的整联蛋白I结构域多肽。 本发明还提供了利用本发明的修饰的整联蛋白I结构域的筛选测定和治疗方法。