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28 条记录 (耗时 0.049 秒)

    Toxin peptide therapeutic agents
    1.
    发明申请
    Toxin peptide therapeutic agents 有权

    公开(公告)号：US20070071764A1

    公开(公告)日：2007-03-29

    申请号：US11406454

    申请日：2006-04-17

    申请人： John Sullivan ,  Joseph McGivern ,  Leslie Miranda ,  Hung Nguyen ,  Kenneth Walker ,  Shaw-Fen Hu ,  Colin Gegg ,  Stefan McDonough

    发明人： John Sullivan ,  Joseph McGivern ,  Leslie Miranda ,  Hung Nguyen ,  Kenneth Walker ,  Shaw-Fen Hu ,  Colin Gegg ,  Stefan McDonough

    IPC分类号： A61K39/395 ,  C07K16/46

    CPC分类号： A61K47/48215 ,  A61K38/00 ,  A61K47/60 ,  C07K14/43504 ,  C07K2319/30 ,  C07K2319/55

    摘要： Disclosed is a composition of matter of the formula (X1)a—(F1)d—(X2)b—(F2)e—(X3)c  (I) and multimers thereof, in which F1 and F2 are half-life extending moieties, and d and e are each independently 0 or 1, provided that at least one of d and e is 1; X1, X2, and X3 are each independently -(L)f-P-(L)g-, and f and g are each independently 0 or 1; P is a toxin peptide of no more than about 80 amino acid residues in length, comprising at least two intrapeptide disulfide bonds; L is an optional linker; and a, b, and c are each independently 0 or 1, provided that at least one of a, b and c is 1. Linkage to the half-life extending moiety or moieties increases the in vivo half-life of the toxin peptide, which otherwise would be quickly degraded. A pharmaceutical composition comprises the composition and a pharmaceutically acceptable carrier. Also disclosed are a DNA encoding the inventive composition of matter, an expression vector comprising the DNA, and a host cell comprising the expression vector. Methods of treating an autoimmune disorder, such as, but not limited to, multiple sclerosis, type 1 diabetes, psoriasis, inflammatory bowel disease, contact-mediated dermatitis, rheumatoid arthritis, psoriatic arthritis, asthma, allergy, restinosis, systemic sclerosis, fibrosis, scleroderma, glomerulonephritis, Sjogren syndrome, inflammatory bone resorption, transplant rejection, graft-versus-host disease, and lupus and of preventing or mitigating a relapse of a symptom of multiple sclerosis are also disclosed.

    Modified Fc molecules
    2.
    发明申请
    Modified Fc molecules 有权
    修饰的Fc分子

    公开(公告)号：US20070269369A1

    公开(公告)日：2007-11-22

    申请号：US11502761

    申请日：2006-08-10

    申请人： Colin Gegg ,  Kenneth Walker ,  Leslie Miranda ,  Fei Xiong

    发明人： Colin Gegg ,  Kenneth Walker ,  Leslie Miranda ,  Fei Xiong

    IPC分类号： A61K51/10 ,  C07H21/04 ,  A61K49/00

    CPC分类号： A61K47/48369 ,  A61K38/02 ,  A61K47/60 ,  A61K47/68 ,  A61K47/6817 ,  C07K16/00 ,  C07K17/00 ,  C07K2317/40 ,  C07K2317/52

    摘要： 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.

    摘要翻译： 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。

    Modified Fc molecules
    9.
    发明申请
    Modified Fc molecules 有权
    修饰的Fc分子

    公开(公告)号：US20060140934A1

    公开(公告)日：2006-06-29

    申请号：US11234731

    申请日：2005-09-23

    申请人： Colin Gegg ,  Fei Xiong ,  Karen Sitney

    发明人： Colin Gegg ,  Fei Xiong ,  Karen Sitney

    IPC分类号： A61K39/395 ,  G01N33/53 ,  C40B40/10

    CPC分类号： C07K16/00 ,  C07K2317/21 ,  C07K2317/52 ,  C07K2318/10 ,  C07K2319/30

    摘要： The present invention concerns molecules and a process in which one or more biologically active peptides are incorporated into an Fc domain. In this invention, pharmacologically active compounds may be prepared by a process comprising (a) selecting at least one peptide that modulates the activity of a protein of interest; and (b) preparing a pharmacologic agent comprising an amino acid sequence of the selected peptide in a loop region of an Fc domain. This process may be employed to modify an Fc domain that is already linked through an N— or C-terminus or sidechain to a peptide or to a polypeptide (e.g., etanercept). This process may also be employed to modify an Fc domain that is part of an antibody (e.g., adalimumab, epratuzumab, infliximab, Herceptin®, and the like). In this way, different molecules can be produced that have additional functionalities, such as a binding domain to a different epitope or an additional binding domain to the precursor molecule's existing epitope. The peptide can be selected, for example, by phage display, E. coli display, ribosome display, RNA-peptide screening, yeast-based screening, chemical-peptide screening, rational design, or protein structural analysis.

    摘要翻译： 本发明涉及分子和一种或多种生物活性肽并入Fc结构域的方法。 在本发明中，药理学活性化合物可以通过以下方法制备：（a）选择至少一种调节目的蛋白质活性的肽; 和（b）在Fc结构域的环区中制备包含所选肽的氨基酸序列的药理学试剂。 该方法可以用于修饰已经通过N-或C-末端或侧链连接到肽或多肽（例如依那西普）的Fc结构域。 该方法也可用于修饰作为抗体一部分的Fc结构域（例如阿达木单抗，依普珠单抗，英夫利昔单抗，赫赛汀等）。 以这种方式，可以产生具有额外功能的不同分子，例如与不同表位的结合结构域或与前体分子存在的表位的附加结合结构域。 肽可以例如通过噬菌体展示，大肠杆菌展示，核糖体展示，RNA-肽筛选，酵母筛选，化学肽筛选，合理设计或蛋白质结构分析来选择。