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公开(公告)号：US5506107A
公开(公告)日：1996-04-09
申请号：US122548
申请日：1993-09-29
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 , G01N33/566
CPC分类号： C12N15/8509 , C07K14/505 , C07K14/535 , C07K14/5412 , C07K14/57554 , C07K14/61 , C07K16/2869 , G01N33/74 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2267/03 , A61K38/00 , G01N2333/61
摘要： We have discovered that growth hormones form 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： PCT No.PCT / US92 / 03743 Sec。 371日期：1993年9月29日 102（e）日期1993年9月29日PCT提交1992年5月6日PCT公布。 出版物WO92 / 21029 日期：1992年11月26日。我们发现生长激素与其受体形成三元复合物，其中激素上的位点1首先与一个受体分子结合，然后激素位点2然后结合另一个受体分子，由此产生1 ：2复杂。 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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公开(公告)号：US6057292A
公开(公告)日：2000-05-02
申请号：US28587
申请日：1998-02-24
申请人： Brian C. Cunningham , Henry B. Lowman , James A. Wells , Ross G. Clark , Kenneth Olson , Germaine G. Fuh
发明人： Brian C. Cunningham , Henry B. Lowman , James A. Wells , Ross G. Clark , Kenneth Olson , Germaine G. Fuh
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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3.发明授权Method for identifying active domains and amino acid residues in polypeptides and hormone variants 失效用于鉴定多肽和激素变体中活性结构域和氨基酸残基的方法
公开(公告)号：US06013478A
公开(公告)日：2000-01-11
申请号：US104036
申请日：1998-06-24
IPC分类号： A61K38/24 , C07K1/00 , C07K14/575 , C07K14/61 , C07K16/00 , C12N1/21 , C12N15/00 , C12N15/16 , C12N15/18 , C12N15/63 , C12P21/06 , C12Q1/68 , G01N33/48 , G01N33/50 , G01N33/53 , G01N33/566 , G06F19/00
CPC分类号： C07K14/575 , C12N15/1058 , 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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4.发明授权Human growth hormone variant having enhanced affinity for human growth hormone receptor at site 1 失效人类生长激素变体在位点1具有增强的对人生长激素受体的亲和力
公开(公告)号：US5854026A
公开(公告)日：1998-12-29
申请号：US487110
申请日：1995-06-07
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： A human growth hormone variant including the set of amino acid substitutions H18A, Q22A, F25A, D26A, Q29A, E65A, K168A, E174A is disclosed. Also disclosed is a nucleic acid encoding this variant, along with a vector including the nucleic acid, a host cell including the vector, and a process for preparing the variant. The variant has enhanced affinity for human growth hormone receptor at site 1.
摘要翻译： 公开了一种人生长激素变体，其包括一组氨基酸取代H18A，Q22A，F25A，D26A，Q29A，E65A，K168A，E174A。 还公开了编码该变体的核酸，以及包含核酸的载体，包含载体的宿主细胞，以及制备该变体的方法。 该变体在位点1增强了对人生长激素受体的亲合力。
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公开(公告)号：US06780613B1
公开(公告)日：2004-08-24
申请号：US08479884
申请日：1995-06-07
IPC分类号： C12N121
CPC分类号： C07K14/575 , C12N15/1058 , 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：US5849535A
公开(公告)日：1998-12-15
申请号：US717394
申请日：1996-09-20
申请人： Brian C. Cunningham , Henry B. Lowman , James A. Wells , Ross G. Clark , Kenneth Olson , Germaine G. Fuh
发明人： Brian C. Cunningham , Henry B. Lowman , James A. Wells , Ross G. Clark , Kenneth Olson , Germaine G. Fuh
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, DNA encoding the variants, vectors, host cells, pegylated forms of the variants, as well as methods of making the variants are disclosed.
摘要翻译： 公开了人生长激素变体，编码变体的DNA，载体，宿主细胞，变体的聚乙二醇化形式，以及制备变体的方法。
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7.发明授权
公开(公告)号：US5834250A
公开(公告)日：1998-11-10
申请号：US903398
申请日：1997-06-30
IPC分类号： A61K38/24 , C07K1/00 , C07K14/575 , C07K14/61 , C07K16/00 , C12N1/21 , C12N15/00 , C12N15/16 , C12N15/18 , C12N15/63 , C12P21/06 , C12Q1/68 , G01N33/48 , G01N33/50 , G01N33/53 , G01N33/566 , G06F19/00
CPC分类号： C07K14/575 , C12N15/1058 , 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.
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8.发明授权
公开(公告)号：US5766854A
公开(公告)日：1998-06-16
申请号：US483039
申请日：1995-06-06
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.
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9.发明授权Human growth hormone variants having greater affinity for human growth hormone receptor at site 1 失效在位点1对人生长激素受体具有更高亲和力的人生长激素变体
公开(公告)号：US5534617A
公开(公告)日：1996-07-09
申请号：US67160
申请日：1993-05-25
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 , A61K38/25 , C12P21/06
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 are disclosed wherein the lysine at position 41 and/or the leucine at position 45 of native human growth hormone, numbered from the mature N-terminus of native human growth hormone, has been replaced with another amino acid. Also claimed are combination variants that have a higher binding affinity to the growth hormone receptor than wild-type human growth hormone.
摘要翻译： 公开了人生长激素变体，其中天然人生长激素的编号自天然人生长激素的成熟N末端的位置41的赖氨酸和/或第45位的亮氨酸已被另一个氨基酸替代。 还要求的是与野生型人生长激素相比具有比生长激素受体更高的结合亲和力的组合变体。
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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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