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    • 7. 发明申请
    • Albumin-fused kunitz domain peptides
    • 白蛋白融合kunitz结构域肽
    • US20050222023A1
    • 2005-10-06
    • US10503834
    • 2003-02-07
    • Hans-Peter HauserThomas WeimerVal RombergScott KeeDarrell SleepRobert LadnerArthur Ley
    • Hans-Peter HauserThomas WeimerVal RombergScott KeeDarrell SleepRobert LadnerArthur Ley
    • C07K14/675C12N15/62
    • C12N15/62C07K2319/31
    • The invention relates to proteins comprising serine protease inhibiting peptides, such as Kunitz domain peptides (including, but not limited to, fragments and variants thereof) fused to albumin, or fragments or variants thereof. These fusion proteins are herein collectively referred to as “albumin fusion proteins of the invention.” These fusion proteins exhibit extended shelf-life and/or extended or therapeutic activity in solution. The invention encompasses, therapeutic albumin fusion proteins, compositions, pharmaceutical compositions, formulations and kits. The invention also encompasses nucleic acid molecules encoding the albumin fusion proteins of the invention, as well as vectors containing these nucleic acids, host cells transformed with these nucleic acids and vectors, and methods of making the albumin fusion proteins of the invention using these nucleic acids, vectors, and/or host cells. The invention also relates to compositions and methods for inhibiting neutrophil elastase, kallikrein, and plasmin. The invention further relates to compositions and methods for treating cystic fibrosis and cancer.
    • 本发明涉及包含丝氨酸蛋白酶抑制肽的蛋白质,例如与白蛋白或其片段或变体融合的Kunitz结构域肽(包括但不限于其片段和变体)。 这些融合蛋白在本文中统称为“本发明的白蛋白融合蛋白”。 这些融合蛋白在溶液中表现出延长的保质期和/或延长或治疗活性。 本发明包括治疗性白蛋白融合蛋白,组合物,药物组合物,制剂和试剂盒。 本发明还包括编码本发明的白蛋白融合蛋白的核酸分子以及含有这些核酸的载体,用这些核酸和载体转化的宿主细胞,以及使用这些核酸制备本发明的白蛋白融合蛋白的方法 ,载体和/或宿主细胞。 本发明还涉及抑制嗜中性粒细胞弹性蛋白酶,激肽释放酶和纤溶酶的组合物和方法。 本发明还涉及治疗囊性纤维化和癌症的组合物和方法。
    • 8. 发明申请
    • DIRECTED EVOLUTION OF NOVEL BINDING PROTEINS
    • 新型结合蛋白的指导进化
    • US20070259417A1
    • 2007-11-08
    • US11745199
    • 2007-05-07
    • Robert LadnerSonia GutermanBruce RobertsWilliam MarklandArthur LeyRachel Kent
    • Robert LadnerSonia GutermanBruce RobertsWilliam MarklandArthur LeyRachel Kent
    • C12N1/08
    • C40B40/02A61K8/64A61K38/00A61K2800/57A61Q11/00C07K1/047C07K14/43522C07K14/8114C07K14/8117C12N7/00C12N15/1037C12N2795/18111
    • In order to obtain a novel binding protein against a chosen target, DNA molecules, each encoding a protein comprising one of a family of similar potential binding domains and a structural signal calling for the display of the protein on the outer surface of a chosen bacterial cell, bacterial spore or phage (genetic package) are introduced into a genetic package. The protein is expressed and the potential binding domain is displayed on the outer surface of the package. The cells or viruses bearing the binding domains which recognize the target molecule are isolated and amplified. The successful binding domains are then characterized. One or more of these successful binding domains is used as a model for the design of a new family of potential binding domains, and the process is repeated until a novel binding domain having a desired affinity for the target molecule is obtained. In one embodiment, the first family of potential binding domains is related to bovine pancreatic trypsin inhibitor, the genetic package is M13 phage, and the protein includes the outer surface transport signal of the M13 gene III protein.
    • 为了获得针对所选靶标的新型结合蛋白,每个编码包含相似潜在结合结构域的家族之一的蛋白质的DNA分子和要求在选择的细菌细胞的外表面上显示蛋白质的结构信号 ,细菌孢子或噬菌体(遗传包装)被引入到遗传包装中。 蛋白质被表达,并且潜在的结合结构域显示在包装的外表面上。 分离和扩增具有识别靶分子的结合域的细胞或病毒。 然后表征成功的结合结构域。 将这些成功结合结构域中的一个或多个用作设计新的潜在结合结构域家族的模型,并重复该过程,直到获得对靶分子具有所需亲和力的新结合结构域。 在一个实施方案中,第一潜在结合域家族与牛胰蛋白酶抑制剂有关,遗传包是M13噬菌体,蛋白质包括M13基因III蛋白的外表面转运信号。