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61. 发明授权

US4881175A Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides 失效
标题翻译：用于确定和显示将双链或多链多肽转化为单链多肽的可能的化学结构的基于计算机的系统和方法
公开(公告)号：US4881175A
公开(公告)日：1989-11-14
申请号：US204940
申请日：1988-06-09
申请人： Robert C. Ladner
发明人： Robert C. Ladner
IPC分类号： C07K1/00 , G06F17/50
CPC分类号： C07K1/00 , G06F19/16 , G06F19/22 , Y10S706/932
摘要： A computer based system and method determines and displays possible chemical structures for converting two naturally aggregated but chemically separated polypeptide chains into a single polypeptide chain which will fold into a three dimensional structure very similar to the original structure made of the two polypeptide chains. A data base contains a large number of amino acid sequences for which the three dimensional structure is known. After plausible sites have been selected, this data base is examined to find which amino acid sequences (linkers) can bridge the gap between the plausible sites to create a plausible one-polypeptide structure. The testing of each possible linker proceeds in three steps. First, the span (a scalar quantity) of the candidate is compared to the span of the gap. If the span is close enough, step two is done which involves aligning the first peptides of the candidate with the initial peptide of the gap. The three dimensional vector from tail to head of the candidate is compared to the three dimensional vector from tail to head of the gap. If there is a sufficient match between the two vectors, step three is done, which involves fitting the termini of the candidate (using, for example, a least squares procedure) to the termini of the gap. If these two termini fit well enough, the candidate is enrolled for a ranking process.
摘要翻译：基于计算机的系统和方法确定并显示用于将两个天然聚集但化学分离的多肽链转化成单个多肽链的可能的化学结构，其将折叠成与由两条多肽链构成的原始结构非常相似的三维结构。数据库包含大量已知三维结构的氨基酸序列。在选择合适的位点后，检查该数据库以找出哪些氨基酸序列（接头）可以弥合可信位点之间的间隙，以产生合理的单多肽结构。每个可能的接头的测试分三步进行。首先，将候选者的跨度（标量）与间隙的跨度进行比较。如果跨度足够接近，则进行第二步，其包括将候选物的第一个肽与间隙的初始肽对齐。从候选人的尾部到头部的三维向量与从间隙的尾部到头部的三维向量进行比较。如果两个向量之间存在足够的匹配，则完成步骤3，这涉及将候选者的终端（例如使用最小二乘法）适配到间隙的终点。如果这两个终端足够好，候选人将被注册进行排名过程。

62. 发明授权

US4704692A Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides 失效
标题翻译：用于确定和显示将双链或多链多肽转化为单链多肽的可能的化学结构的基于计算机的系统和方法
公开(公告)号：US4704692A
公开(公告)日：1987-11-03
申请号：US902970
申请日：1986-09-02
申请人： Robert C. Ladner
发明人： Robert C. Ladner
IPC分类号： C07K1/00 , G06F17/50 , G06F15/46 , G01N33/00
CPC分类号： C07K1/00 , G06F19/16 , G06F19/22 , Y10S706/906
摘要： A computer based system and method determines, and displays possible chemical structures for converting two naturally aggregated but chemically separated polypeptide chains into a single polypeptide chain which will fold into a three dimensional structure very similar to the original structure made of the two polypeptide chains. A data base contains a large number of amino acid sequences for which the three dimensional structure is known. After plausible sites have been selected, this data base is examined to find which amino acid sequences (linkers) can bridge the gap between the plausible sites to create a plausible one-polypeptide structure. The testing of each possible linker proceeds in three steps. First, the span (a scaler quantity) of the candidate is compared to the span of the gap. If the span is close enough, step two is done which involves aligning the first peptides of the candidate with the initial peptide of the gap. The three dimensional vector from tail to head of the candidate is compared to the three dimensional vector from tail to head of the gap. If there is a sufficient match between the two vectors, step three is done, which involves fitting the termini of the candidate (using, for example, at least squares procedure) to the termini of the gap. If these two termini fit well enough, the candidate is enrolled for a ranking process.
摘要翻译：基于计算机的系统和方法确定并显示用于将两个天然聚集但化学分离的多肽链转化成单个多肽链的可能化学结构，其将折叠成与由两条多肽链构成的原始结构非常相似的三维结构。数据库包含大量已知三维结构的氨基酸序列。在选择合适的位点后，检查该数据库以找出哪些氨基酸序列（接头）可以弥合可信位点之间的间隙，以产生合理的单多肽结构。每个可能的接头的测试分三步进行。首先，将候选者的跨度（缩放器数量）与间隙的跨度进行比较。如果跨度足够接近，则进行第二步，其包括将候选物的第一个肽与间隙的初始肽对齐。从候选人的尾部到头部的三维向量与从间隙的尾部到头部的三维向量进行比较。如果两个向量之间存在足够的匹配，则完成步骤3，其涉及将候选者的终端（例如，至少使用平方子程序）拟合到间隙的末尾。如果这两个终端足够好，候选人将被注册进行排名过程。

63. 发明授权

US09873957B2 Libraries of genetic packages comprising novel HC CDR3 designs 有权
公开(公告)号：US09873957B2
公开(公告)日：2018-01-23
申请号：US12922153
申请日：2009-03-13
申请人： Robert C. Ladner
发明人： Robert C. Ladner
IPC分类号： C40B50/06 , C40B40/08 , C07K16/00 , C07K16/12 , C07K16/28
CPC分类号： C40B40/08 , C07K16/005 , C07K16/1275 , C07K16/28 , C07K2317/565 , C40B50/06
摘要： Provided are compositions and methods for preparing and identifying antibodies having CDR3s that vary in sequence and in length from very short to very long which in certain embodiments may bind to a carbohydrate moiety or the active site of an enzyme. Libraries coding for antibodies with the CDR3s are also provided. The libraries can be provided by modifying a pre-existing nucleic acid library.

64. 发明授权

US09388510B2 Libraries of genetic packages comprising novel HC CDR1, CDR2, and CDR3 and novel LC CDR1, CDR2, and CDR3 designs 有权
标题翻译：包含新型HC CDR1，CDR2和CDR3以及新型LC CDR1，CDR2和CDR3设计的遗传包装库
公开(公告)号：US09388510B2
公开(公告)日：2016-07-12
申请号：US12989307
申请日：2009-04-24
申请人： Robert C. Ladner
发明人： Robert C. Ladner
IPC分类号： C40B40/08 , C40B40/02 , C07K16/00
CPC分类号： C07K16/005 , C07K2317/565 , C40B40/02 , C40B40/08 , C40B40/10
摘要： Provided are compositions and methods for preparing and identifying antibodies having CDR3s that vary in sequence and in length from very short to very long which in certain embodiments may bind to a carbohydrate moiety or the active site of an enzyme. Libraries coding for antibodies with the CDR3s are also provided. The libraries can be provided by modifying a pre-existing nucleic acid library.
摘要翻译：提供了用于制备和鉴定具有CDR3的抗体的组合物和方法，所述抗体具有从非常短到非常长的序列和长度，其在某些实施方案中可能结合于碳水化合物部分或酶的活性位点。还提供了编码具有CDR3的抗体的文库。可以通过修饰预先存在的核酸文库来提供文库。

65. 发明授权

US08431359B2 Nucleic acids encoding polypeptide inhibitors of human plasmin derived from the Kunitz domains 失效
标题翻译：编码来自Kunitz结构域的人纤溶酶多肽抑制剂的核酸
公开(公告)号：US08431359B2
公开(公告)日：2013-04-30
申请号：US11083742
申请日：2005-03-18
申请人： William Markland , Robert C. Ladner
发明人： William Markland , Robert C. Ladner
IPC分类号： C12P21/06
CPC分类号： C04B35/5935 , C07K14/8114
摘要： This invention features novel proteins that are homologous to the first Kunitz domain (K1) of lipoprotein-associated coagulation inhibitor (LACI), and are capable of inhibiting plasmin and nucleic acids encoding these proteins. The invention also features the use of such proteins in therapeutic, diagnostic, and clinical methods.
摘要翻译：本发明的特征在于与脂蛋白相关的凝血抑制剂（LACI）的第一Kunitz结构域（K1）同源的新型蛋白质，并能够抑制编码这些蛋白质的纤溶酶和核酸。本发明还涉及这些蛋白质在治疗，诊断和临床方法中的应用。

66. 发明申请

US20110172125A1 LIBRARIES OF GENETIC PACKAGES COMPRISING NOVEL HC CDR1, CDR2, AND CDR3 AND NOVEL LC CDR1, CDR2, AND CDR3 DESIGNS 有权
标题翻译：包含新型HC CDR1，CDR2和CDR3和新型LC CDR1，CDR2和CDR3设计的遗传包装图
公开(公告)号：US20110172125A1
公开(公告)日：2011-07-14
申请号：US12989307
申请日：2009-04-24
申请人： Robert C. Ladner
发明人： Robert C. Ladner
IPC分类号： C40B40/08 , C40B50/00
CPC分类号： C07K16/005 , C07K2317/565 , C40B40/02 , C40B40/08 , C40B40/10
摘要： Provided are compositions and methods for preparing and identifying antibodies having CDR3s that vary in sequence and in length from very short to very long which in certain embodiments may bind to a carbohydrate moiety or the active site of an enzyme. Libraries coding for antibodies with the CDR3s are also provided. The libraries can be provided by modifying a pre-existing nucleic acid library.
摘要翻译：提供了用于制备和鉴定具有CDR3的抗体的组合物和方法，所述抗体具有从非常短到非常长的序列和长度，其在某些实施方案中可能结合于碳水化合物部分或酶的活性位点。还提供了编码具有CDR3的抗体的文库。可以通过修饰预先存在的核酸文库来提供文库。

67. 发明授权

US07851442B2 Prevention and reduction of blood loss 有权
标题翻译：预防和减少失血
公开(公告)号：US07851442B2
公开(公告)日：2010-12-14
申请号：US11931373
申请日：2007-10-31
申请人： Robert C. Ladner , Arthur C. Ley
发明人： Robert C. Ladner , Arthur C. Ley
IPC分类号： A61K38/16 , C07K14/00
CPC分类号： A61K38/57 , A61K9/0019 , A61K38/55 , C12N9/6445
摘要： Kits containing a dry lyophilized kallikrein inhibitor are described.
摘要翻译：描述了含有干燥冻干激肽释放酶抑制剂的试剂盒。

68. 发明授权

US07628983B2 Kallikrein-binding “Kunitz domain” proteins and analogues thereof 失效
标题翻译：激肽释放酶结合“Kunitz结构域”蛋白及其类似物
公开(公告)号：US07628983B2
公开(公告)日：2009-12-08
申请号：US11365438
申请日：2006-03-01
申请人： William Markland , Robert C. Ladner
发明人： William Markland , Robert C. Ladner
IPC分类号： A61K38/43 , A61K38/00 , A01N37/18 , C12Q1/00 , C12P21/04
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.
摘要翻译：本发明提供了能够结合激肽释放酶的Kunitz结构域的新型蛋白质同源物; 编码这种新蛋白质的多核苷酸; 和含有这些多核苷酸的载体和转化的宿主细胞。

69. 发明申请

US20090221480A1 Kallikrein Inhibitors and Anti-Thrombolytic Agents and Uses Thereof 审中-公开
公开(公告)号：US20090221480A1
公开(公告)日：2009-09-03
申请号：US11931665
申请日：2007-10-31
申请人： Henry Blair , Thomas Beck , Robert C. Ladner
发明人： Henry Blair , Thomas Beck , Robert C. Ladner
IPC分类号： A61K38/17 , A61P7/00
CPC分类号： A61K38/55 , A61K31/195 , A61K38/57 , A61K45/06 , A61K2300/00
摘要： Methods, kits and compositions are described that include a non-naturally occurring kallikrein inhibitor and an anti-thrombolytic agent, e.g., an anti-fibrinolytic agent, for preventing or reducing blood loss and/or ischemia, e.g., ischemia associated with perioperative blood loss and cerebral ischemia, the onset of systemic inflammatory response, and/or reperfusion injury, e.g., reperfusion injury associated with cerebral ischemia or a focal brain ischemia, e.g., in patients subjected to invasive surgical procedures, especially procedures requiring cardiopulmonary bypass.

70. 发明申请

US20090062195A1 Kallikrein-Inhibitor Therapies 审中-公开
标题翻译：激肽释放酶抑制剂治疗
公开(公告)号：US20090062195A1
公开(公告)日：2009-03-05
申请号：US11929876
申请日：2007-10-30
申请人： Robert C. Ladner , Arthur C. Ley , Shirish Hirani , Anthony Williams , Maria Grazia De Simoni , Luigi Bergamaschini
发明人： Robert C. Ladner , Arthur C. Ley , Shirish Hirani , Anthony Williams , Maria Grazia De Simoni , Luigi Bergamaschini
IPC分类号： A61K38/55 , A61P9/10
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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