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1. 发明申请

US20060264603A1 Kallikrein-binding "Kunitz domain" proteins and analogues thereof 失效
公开(公告)号：US20060264603A1
公开(公告)日：2006-11-23
申请号：US11365438
申请日：2006-03-01
申请人： William Markland , Robert Ladner
发明人： William Markland , Robert Ladner
IPC分类号： A61K38/54 , G01N33/53 , C12N9/99
CPC分类号： C07K14/8117 , A61K38/00 , C07K14/8114 , G01N2333/8114 , G01N2333/96455
摘要： This invention provides: novel protein homologous of a Kunitz domain, which are capable of binding kallikrein; polynucleotides that encode such novel proteins; and vectors and transformed host cells containing these polynucleotides.

2. 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。

3. 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.

4. 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。

5. 发明申请

US20050186649A1 Inhibitors of human plasmin derived from the kunitz domains 失效
标题翻译：人类纤溶酶抑制剂衍生自kunitz结构域
公开(公告)号：US20050186649A1
公开(公告)日：2005-08-25
申请号：US11083742
申请日：2005-03-18
申请人： William Markland , Robert Ladner
发明人： William Markland , Robert Ladner
IPC分类号： C12N15/09 , A61K38/55 , A61K38/57 , A61K51/00 , A61P7/04 , C04B35/593 , C07K14/81 , C12N9/68 , C12Q1/37 , C12Q1/56 , C07H21/04 , C12N9/99
CPC分类号： C04B35/5935 , C07K14/8114
摘要： This invention provides: novel proteins, which are homologous to the first Kunitz domain (K1) of lipoprotein-associated coagulation inhibitor (LACI), and which are capable of inhibiting plasmin; uses of such novel proteins in therapeutic, diagnostic, and clinical methods; and polynucleotides that encode such novel proteins.
摘要翻译：本发明提供了与脂蛋白相关凝血抑制剂（LACI）的第一Kunitz结构域（K1）同源的能够抑制纤溶酶的新型蛋白质; 在治疗，诊断和临床方法中使用这种新型蛋白质; 和编码这种新蛋白质的多核苷酸。

6. 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。

7. 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。

8. 发明申请

US20060257937A1 Focused libraries of genetic packages 审中-公开
公开(公告)号：US20060257937A1
公开(公告)日：2006-11-16
申请号：US11416460
申请日：2006-05-01
申请人： Robert Ladner
发明人： Robert Ladner
IPC分类号： C40B30/06 , C40B40/10 , G01N33/53
CPC分类号： C12N15/1037 , C07K16/00 , C07K16/005 , C07K2317/565 , C40B40/02 , C40B40/08 , C40B40/10
摘要： Focused libraries of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of antibody peptides, polypeptides or proteins and collectively display, display and express, or comprise at least a portion of the focused diversity of the family. The libraries have length and sequence diversities that mimic that found in native human antibodies.

9. 发明申请

US20060234302A1 Libraries and methods for isolating antibodies 失效
公开(公告)号：US20060234302A1
公开(公告)日：2006-10-19
申请号：US11346403
申请日：2006-02-01
申请人： Rene Hoet , Sonia Schoonbroodt , Robert Ladner
发明人： Rene Hoet , Sonia Schoonbroodt , Robert Ladner
IPC分类号： C40B30/04
CPC分类号： C07K16/005 , C07K16/00 , C07K16/18 , C07K16/2896 , C07K2317/21 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C40B30/04
摘要： The disclosure features methods for identifying antibodies that bind to a carbohydrate moiety. Libraries coding for antibodies that bind to a carbohydrate moiety are provided. The libraries can be provided by modifying a pre-existing nucleic acid library. Antibodies that bind to a carbohydrate moiety are described.

10. 发明申请

US20060051764A1 Thymidylate synthase polymorphisms for use in screening for cancer susceptibility 审中-公开
标题翻译：用于筛选癌症易感性的胸苷酸合酶多态性
公开(公告)号：US20060051764A1
公开(公告)日：2006-03-09
申请号：US10532201
申请日：2003-10-21
申请人： Michael Mandola , Jan Stoehlmacher , Heinz-Josef Lenz , Robert Ladner
发明人： Michael Mandola , Jan Stoehlmacher , Heinz-Josef Lenz , Robert Ladner
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C12Q1/6886 , C12Q2600/106 , C12Q2600/156 , C12Q2600/172
摘要： The present invention discloses a novel single nucleotide polymorphism (SNP) in the isolated 5′ tandem repeats of the thymidylate synthase (TS) gene and methods for its use. The novel SNP, located in the 12th nucleotide of a 28 bp third tandem repeat (3R) of the TS gene, substitutes a C for a G, and is the variant form of the repeat. Subjects with the wild-type form of 3R have greater transcription of the TS gene than subjects with the variant form. The invention also reveals that a six base pair deletion in the 3′ region of TS (−6 bp/1494) indicates mRNA instability and thus reduced production of TS. In diseased tissue, such as cancer, reduced production of TS is beneficial because it prevents the cancerous cells from growing and spreading. Analysis of either polymorphism or both together allows for prediction of a subject's response to chemotherapeutic and anti-cardiovascular disease treatments because both diseases are related to TS levels in a subject.
摘要翻译：本发明公开了在胸苷酸合酶（TS）基因的分离的5'串联重复中的新型单核苷酸多态性（SNP）及其使用方法。位于TS基因的28bp第三串联重复（3R）的第12个核苷酸的新型SNP代替C代表G，并且是重复的变体形式。具有野生型形式的3R的受试者比具有变体形式的受试者具有更高的TS基因转录。本发明还揭示了在TS（-6bp / 1494）的3'区域中的6个碱基对缺失表示mRNA不稳定性，从而降低TS的产生。在患病组织如癌症中，减少TS的产生是有益的，因为它可防止癌细胞生长和扩散。多态性或两者的分析可以预测受试者对化学治疗和抗心血管疾病治疗的反应，因为这两种疾病都与受试者的TS水平相关。

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