公开(公告)号：US07118879B2

公开(公告)日：2006-10-10

申请号：US10126544

申请日：2002-04-22

申请人： Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

发明人： Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

IPC分类号： C12Q1/68

CPC分类号： C40B40/02 ,  A61K38/00 ,  C07K1/047 ,  C07K1/107 ,  C07K14/43522 ,  C07K14/805 ,  C07K14/8114 ,  C07K14/8117 ,  C12N7/00 ,  C12N15/1037 ,  C12N2795/14111 ,  C12N2795/14122 ,  C12N2795/14143

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。

公开(公告)号：US5663143A

公开(公告)日：1997-09-02

申请号：US358160

申请日：1994-12-16

申请人： Arthur Charles Ley ,  Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Rachel Baribault Kent

发明人： Arthur Charles Ley ,  Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Rachel Baribault Kent

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/55 ,  A61P11/00 ,  A61Q11/00 ,  C07K1/04 ,  C07K14/435 ,  C07K14/805 ,  C07K14/81 ,  C12N1/19 ,  C12N15/10 ,  C12N15/15 ,  C12P21/02 ,  C40B40/02

CPC分类号： C07K1/047 ,  C07K14/43522 ,  C07K14/805 ,  C07K14/8114 ,  C12N15/1037 ,  C40B40/02 ,  A61K38/00

摘要： Certain Kunitz domain derived proteins which bind and inhibit human neutrophil elastase with a K.sub.i of less than 10 picomolar are described.

摘要翻译： 描述了结合并抑制Ki小于10皮摩尔的人嗜中性粒细胞弹性蛋白酶的某些Kunitz结构域衍生的蛋白质。

公开(公告)号：US20090234101A1

公开(公告)日：2009-09-17

申请号：US12255793

申请日：2008-10-22

申请人： ROBERT CHARLES LADNER ,  SONIA KOSOW GUTERMAN ,  BRUCE LINDSY ROBERTS ,  WILLIAM MARKLAND ,  ARTHUR CHARLES LEY ,  RACHEL BARIBAULT KENT

发明人： ROBERT CHARLES LADNER ,  SONIA KOSOW GUTERMAN ,  BRUCE LINDSY ROBERTS ,  WILLIAM MARKLAND ,  ARTHUR CHARLES LEY ,  RACHEL BARIBAULT KENT

IPC分类号： C07K14/00 ,  C40B40/10 ,  C07H21/04 ,  C40B30/04

CPC分类号： C07K14/43504 ,  A61K38/00 ,  A61K2800/57 ,  C07K1/047 ,  C07K14/00 ,  C07K14/245 ,  C07K14/43522 ,  C07K14/43572 ,  C07K14/811 ,  C07K14/8114 ,  C07K2319/00 ,  C07K2319/02 ,  C12N7/00 ,  C12N15/1037 ,  C12N2795/14022 ,  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。

公开(公告)号：US07893007B2

公开(公告)日：2011-02-22

申请号：US12255793

申请日：2008-10-22

申请人： Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

发明人： Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

IPC分类号： C40B30/04

CPC分类号： C07K14/43504 ,  A61K38/00 ,  A61K2800/57 ,  C07K1/047 ,  C07K14/00 ,  C07K14/245 ,  C07K14/43522 ,  C07K14/43572 ,  C07K14/811 ,  C07K14/8114 ,  C07K2319/00 ,  C07K2319/02 ,  C12N7/00 ,  C12N15/1037 ,  C12N2795/14022 ,  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。

公开(公告)号：US5837500A

公开(公告)日：1998-11-17

申请号：US415922

申请日：1995-04-03

申请人： Robert Charles Ladner ,  Sonia Kosow Gutterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

发明人： Robert Charles Ladner ,  Sonia Kosow Gutterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

IPC分类号： A61K8/64 ,  A61K38/00 ,  A61Q11/00 ,  C07K1/04 ,  C07K1/107 ,  C07K14/435 ,  C07K14/805 ,  C07K14/81 ,  C12N1/21 ,  C12N7/00 ,  C12N7/01 ,  C12N15/10 ,  C40B40/02 ,  C12N15/62 ,  C07K19/00

CPC分类号： C40B40/02 ,  C07K1/047 ,  C07K1/107 ,  C07K14/43522 ,  C07K14/805 ,  C07K14/8114 ,  C07K14/8117 ,  C12N15/1037 ,  C12N7/00 ,  A61K38/00 ,  C12N2795/14111 ,  C12N2795/14122 ,  C12N2795/14143

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.

公开(公告)号：US07413537B2

公开(公告)日：2008-08-19

申请号：US10207797

申请日：2002-07-31

申请人： Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

发明人： Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

IPC分类号： C40B40/02

CPC分类号： C12N15/1037 ,  C40B40/02

摘要： The invention relates, in part, to a library of chimeric proteins, each chimeric protein including a mini-protein between about eight and about forty amino acids long, wherein the mini-protein has a single disulfide bond formed by a pair of invariant cysteines and has only two cysteines. The chimeric protein also includes at least a portion of an outer surface protein of a genetic package, wherein the chimeric protein is displayed on the outer surface of the genetic package. The invention also includes, in part, a mixture of nucleic acids that encode a library of the invention. The invention also includes, in part, a process for identifying proteins with a desired binding activity against a target, the process including screening a library of chimeric proteins of the invention; and identifying the chimeric protein. The invention, in part, also includes chimeric proteins expressed by a library of the invention.

摘要翻译： 本发明部分涉及嵌合蛋白文库，每种嵌合蛋白包括约8至约40个氨基酸长的微型蛋白，其中该微型蛋白具有由一对不变半胱氨酸形成的单一二硫键和 只有两个半胱氨酸。 嵌合蛋白还包括遗传包装的外表面蛋白质的至少一部分，其中嵌合蛋白质显示在遗传包装的外表面上。 本发明还部分包括编码本发明文库的核酸混合物。 本发明还部分包括用于鉴定对靶具有所需结合活性的蛋白质的方法，所述方法包括筛选本发明的嵌合蛋白文库; 并鉴定嵌合蛋白。 本发明部分还包括由本发明的文库表达的嵌合蛋白。

公开(公告)号：US07208293B2

公开(公告)日：2007-04-24

申请号：US09893878

申请日：2001-06-29

申请人： Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

发明人： Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

IPC分类号： C12Q1/68

CPC分类号： C40B40/02 ,  A61K38/00 ,  C07K1/047 ,  C07K1/107 ,  C07K14/43522 ,  C07K14/805 ,  C07K14/8114 ,  C07K14/8117 ,  C12N7/00 ,  C12N15/1037 ,  C12N2795/14111 ,  C12N2795/14122 ,  C12N2795/14143

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。

公开(公告)号：US06979538B2

公开(公告)日：2005-12-27

申请号：US09781988

申请日：2001-02-14

申请人： Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

发明人： Robert Charles Ladner ,  Sonia Kosow Guterman ,  Bruce Lindsay Roberts ,  William Markland ,  Arthur Charles Ley ,  Rachel Baribault Kent

IPC分类号： A61K8/64 ,  A61K38/00 ,  A61Q11/00 ,  C07K1/04 ,  C07K1/107 ,  C07K14/435 ,  C07K14/805 ,  C07K14/81 ,  C12N1/21 ,  C12N7/00 ,  C12N7/01 ,  C12N15/10 ,  C40B40/02 ,  C12Q1/68

CPC分类号： C40B40/02 ,  A61K38/00 ,  C07K1/047 ,  C07K1/107 ,  C07K14/43522 ,  C07K14/805 ,  C07K14/8114 ,  C07K14/8117 ,  C12N7/00 ,  C12N15/1037 ,  C12N2795/14111 ,  C12N2795/14122 ,  C12N2795/14143

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。