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1. 发明申请

US20070259417A1 DIRECTED EVOLUTION OF NOVEL BINDING PROTEINS 审中-公开
标题翻译：新型结合蛋白的指导进化
公开(公告)号：US20070259417A1
公开(公告)日：2007-11-08
申请号：US11745199
申请日：2007-05-07
申请人： Robert Ladner , Sonia Guterman , Bruce Roberts , William Markland , Arthur Ley , Rachel Kent
发明人： Robert Ladner , Sonia Guterman , Bruce Roberts , William Markland , Arthur Ley , Rachel Kent
IPC分类号： C12N1/08
CPC分类号： C40B40/02 , A61K8/64 , A61K38/00 , A61K2800/57 , A61Q11/00 , C07K1/047 , C07K14/43522 , C07K14/8114 , C07K14/8117 , C12N7/00 , C12N15/1037 , C12N2795/18111
摘要： 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.
摘要翻译：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。

2. 发明申请

US20060134087A1 ITI-D1 Kunitz domain mutants as hNE inhibitors 审中-公开
公开(公告)号：US20060134087A1
公开(公告)日：2006-06-22
申请号：US11253176
申请日：2005-10-18
申请人： Arthur Ley , Sonia Guterman , William Markland , Rachel Kent , Bruce Roberts , Robert Ladner
发明人： Arthur Ley , Sonia Guterman , William Markland , Rachel Kent , Bruce Roberts , Robert Ladner
IPC分类号： A61K38/54 , C12N9/99
CPC分类号： A61K38/57 , C07K14/8114
摘要： Mutants of Kunitz domain 1 (ITI-D1) of human inter-α-trypsin inhibitor (ITI), are useful as inhibitors of human neutrophil elastase. Mutants characterized by one or more of the following substitutions (numbered to correspond to bovine pancreatic trypsin inhibitor, the archetypal Kunitz domain) are of particular interest: (a) Val15 or Ile15, (b) Ala16, (c) Phe18, (d) Pro19, (e) Arg1, (f) Pro2, and/or (g) Phe4.

3. 发明申请

US20060084113A1 Directed evolution of disulfide-bonded micro-proteins 有权
标题翻译：二硫键结合微蛋白的定向进化
公开(公告)号：US20060084113A1
公开(公告)日：2006-04-20
申请号：US10207797
申请日：2002-07-31
申请人： Robert Ladner , Sonia Guterman , Bruce Roberts , William Markland , Arthur Ley , Rachel Kent
发明人： Robert Ladner , Sonia Guterman , Bruce Roberts , William Markland , Arthur Ley , Rachel Kent
IPC分类号： C40B40/10
CPC分类号： C12N15/1037 , C40B40/02
摘要： 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.
摘要翻译：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。

4. 发明申请

US20080064637A1 Prevention and reduction of blood loss 审中-公开
标题翻译：预防和减少失血
公开(公告)号：US20080064637A1
公开(公告)日：2008-03-13
申请号：US11796272
申请日：2007-04-27
申请人： Robert Ladner , Arthur Ley , Shirish Hirani , Anthony Williams
发明人： Robert Ladner , Arthur Ley , Shirish Hirani , Anthony Williams
IPC分类号： A61K38/16 , A61P9/10
CPC分类号： A61K38/57 , A61K9/0019 , A61K38/55 , C12N9/6445
摘要： Methods are described for preventing or reducing ischemia and/or systemic inflammatory response in a patient such as perioperative blood loss and/or systemic inflammatory response in a patient subjected to cardiothoracic surgery, e.g. coronary artery bypass grafting and other surgical procedures, especially when such procedures involve extra-corporeal circulation, such as cardiopulmonary bypass.
摘要翻译：描述了用于预防或减少患者中缺血和/或全身炎症反应的方法，例如进行心胸外科手术的患者中的围手术期失血和/或全身炎症反应。冠状动脉旁路移植术等外科手术，特别是当此类手术涉及体外循环，如体外循环时。

5. 发明申请

US20070020252A1 Modified protease inhibitors 审中-公开
标题翻译：改性蛋白酶抑制剂
公开(公告)号：US20070020252A1
公开(公告)日：2007-01-25
申请号：US10570186
申请日：2004-08-30
申请人： Robert Ladner , Aaron Sato , Arthur Ley , Michelle Amaral , Mary Bossard , Michael Roberts , Yan Zhang
发明人： Robert Ladner , Aaron Sato , Arthur Ley , Michelle Amaral , Mary Bossard , Michael Roberts , Yan Zhang
IPC分类号： A61K38/54 , C12N9/99
CPC分类号： C07K14/8114 , A61K38/00 , A61K47/60 , A61K49/0002
摘要： DX-890 inhibits elastase. DX-890 can be attached a single polyethylene glycol moiety. The polyethylene glycol is at least 18 kDa in molecular weight and is attached to the polypeptide by a single covalent bond to the N-terminus of the polypeptide.
摘要翻译： DX-890可抑制弹性蛋白酶。 DX-890可以连接单个聚乙二醇部分。聚乙二醇的分子量至少为18kDa，并且通过与多肽的N末端的单一共价键连接到多肽上。

6. 发明申请

US20060111296A1 Plasmin-inhibitory therapies 审中-公开
标题翻译：纤溶酶抑制疗法
公开(公告)号：US20060111296A1
公开(公告)日：2006-05-25
申请号：US11287121
申请日：2005-11-22
申请人： Laetitia Devy , Arthur Ley , Robert Ladner
发明人： Laetitia Devy , Arthur Ley , Robert Ladner
IPC分类号： A61K38/38
CPC分类号： A61K38/57 , A61K38/38
摘要： The disclosure features a method of treating cancers, angiogenesis-related disorders and lymphangiogenesis-related disorders with plasmin inhibitors. An exemplary method includes: administering, to a subject, a plasmin inhibitor, such as a protein that includes a Kunitz domain that inhibits plasmin.
摘要翻译：该公开内容特征在于用纤溶酶抑制剂治疗癌症，血管发生相关疾病和淋巴管生成相关疾病的方法。一种示例性方法包括：向受试者施用纤溶酶抑制剂，例如包含抑制纤溶酶的Kunitz结构域的蛋白质。

7. 发明申请

US20050222023A1 Albumin-fused kunitz domain peptides 审中-公开
标题翻译：白蛋白融合kunitz结构域肽
公开(公告)号：US20050222023A1
公开(公告)日：2005-10-06
申请号：US10503834
申请日：2003-02-07
申请人： Hans-Peter Hauser , Thomas Weimer , Val Romberg , Scott Kee , Darrell Sleep , Robert Ladner , Arthur Ley
发明人： Hans-Peter Hauser , Thomas Weimer , Val Romberg , Scott Kee , Darrell Sleep , Robert Ladner , Arthur Ley
IPC分类号： C07K14/675 , C12N15/62
CPC分类号： C12N15/62 , C07K2319/31
摘要： 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.
摘要翻译：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

US20050164928A1 Kallikrein-inhibitor therapies 有权
标题翻译：激肽释放酶抑制剂治疗
公开(公告)号：US20050164928A1
公开(公告)日：2005-07-28
申请号：US10953902
申请日：2004-09-27
申请人： Robert Ladner , Arthur Ley , Shirish Hirani , Anthony Williams , Maria De Simoni , Luigi Bergamaschini
发明人： Robert Ladner , Arthur Ley , Shirish Hirani , Anthony Williams , Maria De Simoni , Luigi Bergamaschini
IPC分类号： A61K38/17 , A61K38/54 , C07K14/47
CPC分类号： A61K38/57
摘要： Methods are described for preventing or reducing ischemia, e.g., cerebral ischemia, and/or reperfusion injury, e.g., reperfusion injury associated with cerebral ischemia, in a patient.
摘要翻译：描述了用于预防或减少患者中局部缺血，例如脑缺血和/或再灌注损伤（例如与脑缺血相关的再灌注损伤）的方法。

9. 发明申请

US20050089515A1 Poly-pegylated protease inhibitors 审中-公开
标题翻译：聚聚乙二醇化蛋白酶抑制剂
公开(公告)号：US20050089515A1
公开(公告)日：2005-04-28
申请号：US10931153
申请日：2004-08-30
申请人： Arthur Ley , Aaron Sato , Robert Ladner , Mark Stochl
发明人： Arthur Ley , Aaron Sato , Robert Ladner , Mark Stochl
IPC分类号： A61K38/43 , C07F20060101 , C12N9/99 , C12N15/09
摘要： Disclosed are compounds that comprise: (i) a Kunitz domain polypeptide that comprises a Kunitz domain that binds to and inhibits a protease; and (ii) a plurality of polyethylene glycol moieties attached to the Kunitz domain polypeptide. Each accessible primary amine of the Kunitz domain polypeptide can be attached to one of the moieties. Also disclosed are related methods.
摘要翻译：公开的化合物包括：（i）Kunitz结构域多肽，其包含结合并抑制蛋白酶的Kunitz结构域; 和（ii）连接到Kunitz结构域多肽的多个聚乙二醇部分。 Kunitz结构域多肽的每个可接触的伯胺可以连接到其中一个部分。还公开了相关方法。

10. 发明申请

US20070049522A1 KALLIKREIN-INHIBITOR THERAPIES 有权
标题翻译： KALLIKREIN-INHIBITOR治疗
公开(公告)号：US20070049522A1
公开(公告)日：2007-03-01
申请号：US11466979
申请日：2006-08-24
申请人： Robert Ladner , Arthur Ley , Shirish Hirani , Anthony Williams , Maria De Simoni , Luigi Bergamaschini
发明人： Robert Ladner , Arthur Ley , Shirish Hirani , Anthony Williams , Maria De Simoni , Luigi Bergamaschini
IPC分类号： A61K38/55
CPC分类号： A61K38/57
摘要： Methods are described for preventing or reducing ischemia, e.g., cerebral ischemia, and/or reperfusion injury, e.g., reperfusion injury associated with cerebral ischemia, in a patient.
摘要翻译：描述了用于预防或减少患者中局部缺血，例如脑缺血和/或再灌注损伤（例如与脑缺血相关的再灌注损伤）的方法。

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