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公开(公告)号：US07297334B2
公开(公告)日：2007-11-20
申请号：US10974591
申请日：2004-10-26
IPC分类号： A61K39/395
CPC分类号： C07K16/22 , A61K38/00 , C07K16/005 , C07K2317/24 , C07K2317/55 , C07K2317/56 , C07K2317/565 , C07K2317/569 , C07K2317/73 , C07K2317/92
摘要： Humanized and variant anti-VEGF antibodies and various uses therefor are disclosed. The anti-VEGF antibodies have strong binding affinities for VEGF; inhibit VEGF-induced proliferation of endothelial cells in vitro; and inhibit tumor growth in vivo.
摘要翻译： 公开了人源化和变异的抗VEGF抗体及其各种用途。 抗VEGF抗体对VEGF具有很强的结合亲和力; 体外抑制VEGF诱导的内皮细胞增殖; 并在体内抑制肿瘤生长。
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公开(公告)号：US07169901B2
公开(公告)日：2007-01-30
申请号：US10234671
申请日：2002-09-03
IPC分类号： C07K16/00
CPC分类号： C07K16/22 , A61K2039/505 , C07K2317/24 , C07K2317/55 , C07K2317/565 , C07K2317/567 , C07K2317/73 , C07K2317/92
摘要： Humanized and variant anti-VEGF antibodies and various uses therefor are disclosed. The anti-VEGF antibodies have strong binding affinities for VEGF; inhibit VEGF-induced proliferation of endothelial cells in vitro; and inhibit tumor growth in vivo.
摘要翻译： 公开了人源化和变异的抗VEGF抗体及其各种用途。 抗VEGF抗体对VEGF具有很强的结合亲和力; 体外抑制VEGF诱导的内皮细胞增殖; 并在体内抑制肿瘤生长。
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43.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：US06387638B1
公开(公告)日：2002-05-14
申请号：US09101544
申请日：1998-07-17
申请人： Marcus D. Ballinger , Jennifer T. Jones , Wayne J. Fairbrother , Mark X. Sliwkowski , James A. Wells
发明人： Marcus D. Ballinger , Jennifer T. Jones , Wayne J. Fairbrother , Mark X. Sliwkowski , James A. Wells
IPC分类号： G01N33566
CPC分类号： G01N33/74 , A61K38/00 , C07K14/4756 , G01N2333/485
摘要： The present invention provides heregulin variants that are capable of binding an ErbB receptor. Included in the invention are variants of human heregulins, and, in particular, variants of human heregulin-&bgr;1 having enhanced affinity for the ErbB-3 and ErbB-4 receptors. These variants include at least one amino acid substitution and can include further modifications. The invention also provides nucleic acid molecules encoding heregulin variants and related vectors, host cells, pharmaceutical compositions, and methods.
摘要翻译： 本发明提供能够结合ErbB受体的调节蛋白变体。 本发明中包括本发明的变体，尤其是具有对ErbB-3和ErbB-4受体具有增强亲和性的人类调节蛋白-β1的变体。 这些变体包括至少一个氨基酸取代并且可以包括进一步的修饰。 本发明还提供了编码本领域变体和相关载体的核酸分子，宿主细胞，药物组合物和方法。
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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：US5821047A
公开(公告)日：1998-10-13
申请号：US463587
申请日：1995-06-05
申请人： Lisa J. Garrard , Dennis J. Henner , Steven Bass , Ronald Greene , Henry B. Lowman , James A. Wells , David J. Matthews
发明人： Lisa J. Garrard , Dennis J. Henner , Steven Bass , Ronald Greene , Henry B. Lowman , James A. Wells , David J. Matthews
IPC分类号： A61K47/48 , C07K14/01 , C07K14/47 , C07K14/575 , C07K14/61 , C07K19/00 , C12N5/10 , C12N15/10 , C12N15/11 , C12N15/62 , C12N15/85 , C12Q1/68 , C40B40/02 , G01N33/554 , G01N33/566 , G01N33/74 , C12Q1/70 , C07K16/00 , C12N7/02 , C12N15/63
CPC分类号： C40B40/02 , C07K14/005 , C07K14/575 , C07K14/61 , C12N15/1037 , C12N15/62 , G01N33/6845 , G01N33/74 , C07K2319/00 , C07K2319/02 , C07K2319/735 , C07K2319/75 , C12N2750/00011 , C12N2795/14022 , C12N2795/14122 , G01N2333/61 , Y10S436/802 , Y10S930/12
摘要： A method for selecting novel proteins such as growth hormone and antibody fragment variants having altered binding properties for their respective receptor molecules is provided. The method comprises fusing a gene encoding a protein of interest to the carboxy terminal domain of the gene III coat protein of the filamentous phage M13. The gene fusion is mutated to form a library of structurally related fusion proteins that are expressed in low quantity on the surface of a phagemid particle. Biological selection and screening are employed to identify novel ligands useful as drug candidates. Disclosed are preferred phagemid expression vectors and selected human growth hormone variants.
摘要翻译： 提供了选择新型蛋白质如生长激素和具有改变其各自受体分子的结合特性的抗体片段变体的方法。 该方法包括将编码目的蛋白质的基因融合到丝状噬菌体M13的基因III外壳蛋白的羧基末端结构域上。 基因融合突变以形成在噬菌粒粒子表面上以低量表达的结构相关融合蛋白的文库。 使用生物选择和筛选来鉴定可用作候选药物的新型配体。 公开了优选的噬菌粒表达载体和选择的人生长激素变体。
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50.发明授权
公开(公告)号：US5629173A
公开(公告)日：1997-05-13
申请号：US386000
申请日：1995-02-09
申请人： Lars Abrahmsen , John Burnier , James A. Wells , David Y. Jackson
发明人： Lars Abrahmsen , John Burnier , James A. Wells , David Y. Jackson
摘要： The invention relates to serine protease variants derived from precursor serine proteases via recombinant and/or chemical methods to form protease variants having improved peptide ligase activity. The invention also includes novel ligation substrates which in combination with the serine protease variants and a second ligation substrate are capable of forming a ligation product. The invention also relates to methods for forming such ligation products and the products formed thereby.
摘要翻译： 本发明涉及通过重组和/或化学方法衍生自前体丝氨酸蛋白酶的丝氨酸蛋白酶变体，以形成具有改善的肽连接酶活性的蛋白酶变体。 本发明还包括与丝氨酸蛋白酶变体组合的新型连接底物，第二连接底物能够形成连接产物。 本发明还涉及形成这种连接产品的方法和由此形成的产品。
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