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公开(公告)号：US5665704A
公开(公告)日：1997-09-09
申请号：US451240
申请日：1995-05-25
摘要： Human receptor selective atrial natriuretic factor variants containing various substitutions, especially G16R, show equal potency and binding affinity for the human A-receptor but have decreased affinity for the human clearance or C-receptor. These ANF variants have natriuretic, diuretic and vasorelaxant activity but have increased metabolic stability, making them suitable for treating congestive heart failure, acute kidney failure and renal hypertension.
摘要翻译： 含有各种取代，特别是G16R的人受体选择性心房利钠因子变体对人A受体显示相同的效力和结合亲和力，但对人清除或C-受体的亲和力降低。 这些ANF变体具有利钠，利尿和血管舒张活性，但具有增加的代谢稳定性，使其适合于治疗充血性心力衰竭，急性肾衰竭和肾性高血压。
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公开(公告)号：US06525022B1
公开(公告)日：2003-02-25
申请号：US09154390
申请日：1998-09-16
IPC分类号： A61K3812
摘要： Human receptor selective atrial natriuretic factor variants containing various substitutions, especially G16R, show equal potency and binding affinity for the human A-receptor but have decreased affinity for the human clearance or C-receptor. These ANF variants have natriuretic, diuretic and vasorelaxant activity but have increased metabolic stability, making them suitable for treating congestive heart failure, acute kidney failure and renal hypertension.
摘要翻译： 含有各种取代，特别是G16R的人受体选择性心房利钠因子变体对人A受体显示相同的效力和结合亲和力，但对人清除或C-受体的亲和力降低。 这些ANF变体具有利钠，利尿和血管舒张活性，但具有增加的代谢稳定性，使其适合于治疗充血性心力衰竭，急性肾衰竭和肾性高血压。
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公开(公告)号：US5846932A
公开(公告)日：1998-12-08
申请号：US470846
申请日：1995-06-06
摘要： Human receptor selective atrial natriuretic factor variants containing various substitutions, especially G16R, show equal potency and binding affinity for the human A-receptor but have decreased affinity for the human clearance or C-receptor. These ANF variants have natriuretic, diuretic and vasorelaxant activity but have increased metabolic stability, making them suitable for treating congestive heart failure, acute kidney failure and renal hypertension.
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4.发明授权Variants of native growth hormones having non naturally occurring amino acid sequences or covalent modifications 失效具有非天然存在的氨基酸序列或共价修饰的天然生长激素的变体公开(公告)号：US06800740B1
公开(公告)日：2004-10-05
申请号：US08479883
申请日：1995-06-07
IPC分类号： A61K3827
CPC分类号： C12N15/8509 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2267/03 , A61K38/00 , C07K14/505 , C07K14/535 , C07K14/5412 , C07K14/57554 , C07K14/61 , C07K16/2869 , G01N33/74 , G01N2333/61
摘要： Growth hormones contain two receptor binding sites termed site 1 and site 2 with which they form ternary complexes with their receptors. In this scheme, site 1 on the hormone binds to one molecule of receptor and then site 2 binds to another molecule of receptor, thereby producing a 1:2 complex. Disclosed herein are growth hormone variants consisting of modifications to the native sequence in the region of site 1 or site 2, or alternatively a combination of modifications at both site 1 and site 2.
摘要翻译： 生长激素含有两个受体结合位点，称为位点1和位点2，它们与其受体形成三元复合物。 在该方案中，激素上的位点1与一个受体分子结合，然后位点2与另一个受体分子结合，从而产生1：2复合物。 本文公开了生长激素变体，其包含对位点1或位点2区域中的天然序列的修饰，或者在位点1和位点2处的修饰组合。
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公开(公告)号：US06451561B1
公开(公告)日：2002-09-17
申请号：US08486474
申请日：1995-06-07
IPC分类号： C12N1500
CPC分类号： C40B40/02 , C07K14/575 , C07K14/61 , C07K2319/00 , C07K2319/75 , C12N15/1037 , C12N15/1058 , C12N15/62 , G01N33/6878 , G01N33/74 , G01N2333/61 , Y10S530/806 , Y10S530/808
摘要： The invention provides methods for the systematic analysis of the structure and function of polypeptides by identifying active domains which influence the activity of the polypeptide with a target substance. Such active domains are determined by substituting selected amino acid segments of the polypeptide with an analogous polypeptide segment from an analog to the polypeptide. The analog has a different activity with the target substance as compared to the parent polypeptide. The activities of the segment-substituted polypeptides are compared to the same activity for the parent polypeptide for the target. A comparison of such activities provides an indication of the location of the active domain in the parent polypeptide. The invention also provides methods for identifying the active amino acid residues within the active domain of the parent polypeptide. The method comprises substituting a scanning amino acid for one of the amino acid residues within the active domain of the parent polypeptide and assaying the residue-substituted polypeptide so formed with a target substance. The invention further provides polypeptide variants comprising segment-substituted and residue-substituted growth hormones, prolactins and placental lactogens.
摘要翻译： 本发明提供了通过鉴定影响多肽与靶物质的活性的活性结构域来系统分析多肽的结构和功能的方法。 通过用类似物与多肽的类似多肽片段取代多肽的选定氨基酸片段来确定此类活性结构域。 与亲本多肽相比，类似物与目标物质具有不同的活性。 将段取代的多肽的活性与目标的亲本多肽的相同活性进行比较。 这些活性的比较提供了活性结构域在亲本多肽中的位置的指示。 本发明还提供鉴定亲本多肽活性结构域内活性氨基酸残基的方法。 该方法包括用扫描氨基酸取代母体多肽的活性结构域内的氨基酸残基之一，并测定与靶物质形成的残基取代的多肽。 本发明还提供了包含片段取代的和残基取代的生长激素，催乳素和胎盘乳糖的多肽变体。
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公开(公告)号：US6143523A
公开(公告)日：2000-11-07
申请号：US487107
申请日：1995-06-06
IPC分类号： A61K38/27 , C07K14/01 , C07K14/475 , C07K14/575 , C07K14/61 , C12N1/21 , C12N15/10 , C12N15/18 , C12N15/62 , C12N15/63 , C40B40/02 , G01N33/68 , G01N33/74
CPC分类号： C40B40/02 , A61K38/27 , C07K14/005 , C07K14/575 , C07K14/61 , C12N15/1037 , C12N15/62 , G01N33/6878 , G01N33/74 , C07K2319/00 , C07K2319/02 , C07K2319/735 , C07K2319/75 , C12N2795/14122 , G01N2333/61 , Y10S930/12
摘要： Human growth hormone variants and their nucleic acids are disclosed wherein the amino acid residues at positions 10, 14, 18, 21, 167, 171, 174, 176 and 179 have been replaced with other amino acids. Also claimed are vectors and host cells comprising these human growth hormone variants as well as processes for their preparation.
摘要翻译： 公开了人生长激素变体及其核酸，其中第10,14,18,21,167,171,174,176和179位的氨基酸残基被其它氨基酸替代。 还要求的是包含这些人生长激素变体的载体和宿主细胞以及它们的制备方法。
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公开(公告)号：US6136563A
公开(公告)日：2000-10-24
申请号：US28652
申请日：1998-02-24
IPC分类号： C12N15/09 , A61K31/00 , A61K38/00 , A61K38/27 , A61K47/48 , A61P3/00 , A61P3/10 , A61P5/00 , A61P5/08 , A61P5/12 , A61P13/12 , A61P35/00 , A61P37/00 , A61P43/00 , C07K1/107 , C07K14/61 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/18 , C12N15/63 , C12P21/02 , C12R1/19
CPC分类号： A61K47/48215 , C07K14/61 , A61K38/00 , C07K2319/00 , Y10S514/866 , Y10S930/12
摘要： Human growth hormone variants are disclosed having enhanced affinity for the growth hormone receptor. Also disclosed are human growth hormone variants conjugated to one or more chemical groups, such as poly(ethylene glycol), which is believed to prolong the in vivo half-life of the variants.
摘要翻译： 公开了对生长激素受体具有增强的亲和力的人生长激素变体。 还公开了与一种或多种化学基团缀合的人生长激素变体，例如聚（乙二醇），其被认为延长了变体的体内半衰期。
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公开(公告)号：US6057428A
公开(公告)日：2000-05-02
申请号：US691794
申请日：1996-08-02
申请人： Bruce A. Keyt , Francis Hung Nguyen , Napoleone Ferrara , Brian C. Cunningham , James A. Wells , Bing Li
发明人： Bruce A. Keyt , Francis Hung Nguyen , Napoleone Ferrara , Brian C. Cunningham , James A. Wells , Bing Li
IPC分类号： C12N15/09 , A61K38/00 , A61K38/18 , A61K38/22 , A61P35/00 , C07K14/475 , C07K14/52 , C12N5/10 , C12N15/12 , C12N15/18 , C12Q1/68 , G01N33/50 , G01N33/566 , G01N33/74 , C07K14/71
CPC分类号： C07K14/515 , C07K14/52 , G01N33/74 , A61K38/00 , G01N2500/00
摘要： The present invention involves the preparation of vascular endothelial growth factor (VEGF) variants which provide materials that are selective in respect to binding characteristics to the kinase domain region and the FMS-like tyrosine-kinase region, respectively KDR and FLT-1. The respective KDR and FLT-1 receptors are bound by corresponding domains within the VEGF compound domains. The variants hereof define those two binding regions and modify them so as to introduce changes that interrupt the binding to the respective domain. In this fashion the final biological characteristics of the VEGF molecule are selectively modified.
摘要翻译： 本发明涉及血管内皮生长因子（VEGF）变体的制备，其提供关于与激酶结构域和FMS样酪氨酸激酶区分别为KDR和FLT-1的结合特性有选择性的材料。 相应的KDR和FLT-1受体由VEGF化合物结构域内的相应结构域结合。 其变体定义了这两个绑定区域并对其进行了修改，以便引入中断与相应域的绑定的更改。 以这种方式，VEGF分子的最终生物学特性被选择性地修饰。
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公开(公告)号：US08637646B2
公开(公告)日：2014-01-28
申请号：US10153207
申请日：2002-05-22
IPC分类号： C07K14/475 , C12N15/18 , C12N15/63
CPC分类号： C07K14/575 , C12N15/1058 , Y10S530/806 , Y10S530/808
摘要： The invention provides variants of human growth hormone having an amino acid substitution at amino acid residue R77, numbered from the N-terminus of 191-amino add human growth hormone as well as nucleic acid molecules encoding these variants.
摘要翻译： 本发明提供在氨基酸残基R77具有氨基酸取代的人类生长激素的变体，编号为191-氨基加人生长激素的N末端，以及编码这些变体的核酸分子。
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公开(公告)号：US06936440B1
公开(公告)日：2005-08-30
申请号：US08479886
申请日：1995-06-07
IPC分类号： A01K67/027 , A61K38/00 , A61K38/04 , A61K39/395 , A61P5/02 , A61P5/06 , A61P43/00 , C07K14/505 , C07K14/52 , C07K14/53 , C07K14/535 , C07K14/54 , C07K14/545 , C07K14/55 , C07K14/555 , C07K14/56 , C07K14/565 , C07K14/575 , C07K14/61 , C07K14/705 , C07K16/28 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/12 , C12N15/85 , C12P21/02 , G01N33/15 , G01N33/50 , G01N33/53 , G01N33/542 , G01N33/68 , G01N33/74 , C12N15/18 , C12N15/19
CPC分类号： C12N15/8509 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2267/03 , A61K38/00 , C07K14/505 , C07K14/535 , C07K14/5412 , C07K14/57554 , C07K14/61 , C07K16/2869 , G01N33/74 , G01N2333/61
摘要： We have discovered that growth hormones from ternary complexes with their receptors in which site 1 on the hormone first binds to one molecule of receptor and then hormone site 2 then binds to another molecule of receptor, thereby producing a 1:2 complex. We believe this phenomenon is shared by other ligands having similar conformational structure. Assays based on this phenomenon are useful for identifying ligand agonists and antagonists. Sites 1 and 2 are structurally identified to facilitate generation of amino acid sequence variants of ternary complex-forming ligands. Novel variants of growth hormone, prolactin placental lactogen and other related ligands are provided. As a result of our studies with the ternary complex we have determined that selected antibodies to the receptor for these ligands are capable of acting as ligand agonists or antagonists. Novel growth hormones and novel uses for anti-growth hormone receptor antibodies are described.
摘要翻译： 我们已经发现，来自与其受体的三元复合物的生长激素，其中激素上的位点1首先结合一个受体分子，然后与激素位点2结合，然后结合另一个受体分子，从而产生1：2复合物。 我们认为这种现象由具有相似构象结构的其他配体共享。 基于此现象的分析可用于鉴定配体激动剂和拮抗剂。 在结构上鉴定了位点1和2，以便于产生三元复合物形成配体的氨基酸序列变体。 提供了生长激素，催乳素胎盘乳酸和其他相关配体的新型变体。 作为我们用三元复合物研究的结果，我们确定了这些配体的受体的选定抗体能够作为配体激动剂或拮抗剂。 描述了抗生长激素受体抗体的新型生长激素和新用途。
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