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。

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

IPC分类号： C07K14/61 ,  C12N9/22 ,  C12N9/54 ,  C12P21/02 ,  C12P21/06 ,  C12N9/56 ,  C12P7/62

CPC分类号： C12N9/54 ,  C07K14/61 ,  C12N9/22 ,  C12P21/02

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。

公开(公告)号：US20110052575A1

公开(公告)日：2011-03-03

申请号：US12768089

申请日：2010-04-27

申请人： Manuel Baca ,  James A. Wells ,  Leonard G. Presta ,  Henry B. Lowman ,  Yvonne Man-yee Chen

发明人： Manuel Baca ,  James A. Wells ,  Leonard G. Presta ,  Henry B. Lowman ,  Yvonne Man-yee Chen

IPC分类号： A61K39/395 ,  C07K16/22 ,  A61P35/00

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。

公开(公告)号：US07063961B2

公开(公告)日：2006-06-20

申请号：US10082747

申请日：2002-02-22

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： C12P21/06

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-β1 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.

公开(公告)号：US06429186B1

公开(公告)日：2002-08-06

申请号：US08308879

申请日：1994-09-19

申请人： Germaine Fuh ,  James A. Wells

发明人： Germaine Fuh ,  James A. Wells

IPC分类号： A01N3718

CPC分类号： G01N33/74 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2267/0331 ,  A61K38/00 ,  C07K14/505 ,  C07K14/535 ,  C07K14/5412 ,  C07K14/57554 ,  C07K14/61 ,  C07K14/72 ,  C07K16/2869 ,  C07K2317/73 ,  C12N15/8509 ,  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. Methods for inhibiting the growth of breast cancer cells are also described.

摘要翻译： 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，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。 还描述了抑制乳腺癌细胞生长的方法。

公开(公告)号：US06428954B1

公开(公告)日：2002-08-06

申请号：US08483039

申请日：1995-06-06

申请人： James A. Wells ,  Brian C. Cunningham

发明人： James A. Wells ,  Brian C. Cunningham

IPC分类号： C12Q168

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, prolactens 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。 本发明进一步提供了包含片段取代和残基取代的生长激素，催乳激素和胎盘乳糖的多肽变体。

公开(公告)号：US06271198B1

公开(公告)日：2001-08-07

申请号：US08965056

申请日：1997-11-05

申请人： Andrew C. Braisted ,  J. Kevin Judice ,  Robert S. McDowell ,  J. Christopher Phelan ,  Melissa A. Starovasnik ,  James A. Wells

发明人： Andrew C. Braisted ,  J. Kevin Judice ,  Robert S. McDowell ,  J. Christopher Phelan ,  Melissa A. Starovasnik ,  James A. Wells

IPC分类号： A61K3800

CPC分类号： C07K14/005 ,  A61K38/00 ,  A61K39/00 ,  C12N2740/16122

摘要： Provided are cyclized peptides with a constrained region(s) having an &agr;-helical conformation. Constrained helical peptides having amino acid sequences from HIV gp41 are provided, as is their use in preparing antibodies that prevent viral membrane fusion. Also provided are methods for making such cyclized peptides.

摘要翻译： 提供具有α螺旋构象的约束区域的环化肽。 提供了具有来自HIV gp41的氨基酸序列的约束螺旋肽，以及它们在制备预防病毒膜融合的抗体中的用途。 还提供了制备这种环化肽的方法。

公开(公告)号：US6040136A

公开(公告)日：2000-03-21

申请号：US923854

申请日：1997-09-03

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 ,  C07H17/00 ,  C07K14/00 ,  C12P21/06

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。

公开(公告)号：US6022711A

公开(公告)日：2000-02-08

申请号：US482137

申请日：1995-06-07

申请人： Brian C. Cunningham ,  Henry Lowman ,  James A. Wells

发明人： Brian C. Cunningham ,  Henry Lowman ,  James A. Wells

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： Growth hormone participates in the regulation of normal growth and development processes. The binding affinity of growth hormone for its target receptors is dependent upon the interaction of site 1 and site 2 domains of growth hormone with the target receptor. Embodiments of the present invention include site 1 variants of human growth hormone which bind to target receptors with a different affinity than that of the native hormone. Embodiments of the invention further include components for the production of isolated human growth hormone variants using a host cell/vector expression system.

摘要翻译： 生长激素参与正常生长发育过程的调节。 生长激素对其靶受体的结合亲和力取决于生长激素的位点1和位点2结构域与靶受体的相互作用。 本发明的实施方案包括以不同于天然激素的亲和力结合目标受体的人生长激素的位点1变体。 本发明的实施方案还包括使用宿主细胞/载体表达系统生产分离的人生长激素变体的组分。

公开(公告)号：US5955346A

公开(公告)日：1999-09-21

申请号：US476999

申请日：1995-06-07

申请人： James A. Wells ,  Brian C. Cunningham

发明人： James A. Wells ,  Brian C. Cunningham

IPC分类号： G01N33/53 ,  A61K38/24 ,  A61K38/27 ,  A61P3/10 ,  A61P5/00 ,  A61P5/06 ,  C07K1/00 ,  C07K14/00 ,  C07K14/435 ,  C07K14/47 ,  C07K14/575 ,  C07K14/61 ,  C07K16/00 ,  C12N1/21 ,  C12N5/10 ,  C12N15/00 ,  C12N15/09 ,  C12N15/10 ,  C12N15/12 ,  C12N15/16 ,  C12N15/18 ,  C12N15/62 ,  C12N15/63 ,  C12N15/70 ,  C12P21/02 ,  C12P21/06 ,  C12Q1/68 ,  C12R1/19 ,  C40B40/02 ,  G01N33/48 ,  G01N33/50 ,  G01N33/566 ,  G01N33/68 ,  G01N33/74 ,  G06F19/00

CPC分类号： C40B40/02 ,  C07K14/575 ,  C07K14/61 ,  C12N15/1037 ,  C12N15/1058 ,  C12N15/62 ,  G01N33/6878 ,  G01N33/74 ,  C07K2319/00 ,  C07K2319/75 ,  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。