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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

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。

4. 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。

5. 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。

6. 发明申请

US20070041959A1 POLY-PEGYLATED PROTEASE INHIBITORS 有权
标题翻译：聚乙二醇化蛋白酶抑制剂
公开(公告)号：US20070041959A1
公开(公告)日：2007-02-22
申请号：US11458773
申请日：2006-07-20
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： A61K38/54 , C12N9/99
CPC分类号： C07K14/8114 , A61K47/60 , A61K49/0002
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。

7. 发明申请

US20070031879A1 Novel enterokinase cleavage sequences 审中-公开
标题翻译：新型肠激酶切割序列
公开(公告)号：US20070031879A1
公开(公告)日：2007-02-08
申请号：US11542881
申请日：2006-10-04
申请人： Arthur Ley , Christopher Luneau , Robert Ladner
发明人： Arthur Ley , Christopher Luneau , Robert Ladner
IPC分类号： C40B30/06 , C40B50/06 , C40B40/10 , C07K7/08 , C07K7/06
CPC分类号： C07K7/06 , C07H21/04 , C07K5/1024 , C12N15/1037
摘要： Novel enterokinase cleavage sequences are provided. Also disclosed are methods for the rapid isolation of a protein of interest present in a fusion protein construct including a novel enterokinase cleavage sequence of the present invention and a ligand recognition sequence for capturing the fusion construct on a solid substrate. Preferred embodiments of the present invention show rates of cleavage up to thirty times that of the known enterokinase cleavage substrate (Asp)4-Lys-Ile.
摘要翻译：提供新的肠激酶切割序列。还公开了用于快速分离融合蛋白构建体中包含本发明的新型肠激酶切割序列的目标蛋白质的快速分离方法和用于在固体基质上捕获融合构建体的配体识别序列。本发明的优选实施方案显示分解速率高达已知的肠激酶切割底物（Asp）4 -Lys-Ile的30倍。

8. 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。

9. 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。

10. 发明授权

US5981648A Polymeric curable compositions containing alkylacrylamidoglycolates 失效
标题翻译：含有烷基丙烯酰胺聚糖的聚合物可固化组合物
公开(公告)号：US5981648A
公开(公告)日：1999-11-09
申请号：US913126
申请日：1992-07-13
申请人： Howard Robert Lucas , Robert Gerald Lees , Herbert Burkhard , David Arthur Ley
发明人： Howard Robert Lucas , Robert Gerald Lees , Herbert Burkhard , David Arthur Ley
IPC分类号： C08F20/58 , C08K5/00 , C08K3/00 , C08L33/00
CPC分类号： C08F20/58
摘要： New and improved curable compositions useful as non-yellowing, acid resistant coatings for a variety of substrates and as adhesives and binders are disclosed. The curable compositions comprise a polymeric component comprising poly(C.sub.1 -C.sub.6 alkyl acrylamidoglycolate) functional units and poly (active hydrogen) functional units and preferably an effective amount of a protic acid crosslinking catalyst. In preferred embodiments acid-catalyzed room temperature curable coating compositions are provided. The compositions may be cured effectively at lower temperatures without the use of amines or other toxic crosslinking agents and do not liberate formaldehyde on curing. A method for making poly(C.sub.1 -C.sub.6 alkyl acrylamidoglycolate) functional polymers is also disclosed.
摘要翻译：公开了用作各种基材和粘合剂和粘合剂的非黄变，耐酸涂层的新型和改进的可固化组合物。可固化组合物包含聚合物组分，其包含聚（C 1 -C 6烷基丙烯酰胺基乙酸酯）官能单元和聚（活性氢）官能单元，优选有效量的质子交联催化剂。在优选实施方案中，提供了酸催化的室温可固化涂料组合物。组合物可以在较低温度下有效固化而不使用胺或其它有毒的交联剂，并且在固化时不释放甲醛。还公开了制备聚（C 1 -C 6烷基丙烯酰基羟基乙酸酯）官能聚合物的方法。

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