公开(公告)号：US06566075B1

公开(公告)日：2003-05-20

申请号：US09628188

申请日：2000-07-28

申请人： Jaime A. Escobedo ,  Lewis T. Williams

发明人： Jaime A. Escobedo ,  Lewis T. Williams

IPC分类号： G01N102

CPC分类号： C07K14/71

摘要： A DNA sequence encoding human platelet-derived growth factor receptor (hPDGF-R) has now been isolated and sequenced. An expression construct comprising the sequence encodes a receptor that can be secreted or incorporated into the membrane of a mammalian cell. The incorporated receptor is functionally equivalent to the wild-type receptor, conferring a PDGF-sensitive mitogenic response on cells lacking the receptor. The construct can be used for enhancing PDGF response of cells, determining the regions involved in transducing the signal in response to PDGF binding, providing mutated analogs and evaluating drugs for their physiologic activity.

摘要翻译： 编码人血小板衍生生长因子受体（hPDGF-R）的DNA序列现已被分离并测序。 包含该序列的表达构建体编码可分泌或并入哺乳动物细胞膜的受体。 所掺入的受体在功能上等同于野生型受体，赋予对缺乏受体的细胞的PDGF敏感的促有丝分裂反应。 该构建体可以用于增强细胞的PDGF应答，确定响应于PDGF结合参与转导信号的区域，提供突变的类似物并评价药物的生理活性。

公开(公告)号：US6110737A

公开(公告)日：2000-08-29

申请号：US240294

申请日：1994-05-09

申请人： Jaime A. Escobedo ,  Lewis T. Williams

发明人： Jaime A. Escobedo ,  Lewis T. Williams

IPC分类号： C07K14/435 ,  C07K14/71 ,  C07K14/715 ,  C12N1/19 ,  C12N5/10 ,  C12N5/16 ,  C12N15/63 ,  C12N15/81 ,  C12N15/85 ,  C12Q1/14 ,  G01N1/02 ,  G01N33/53 ,  G01N33/567

CPC分类号： C07K14/71

摘要： A DNA sequence encoding human platelet-derived growth factor receptor (hPDGF-R) has now been isolated and sequenced. An expression construct comprising the sequence encodes a receptor that can be secreted or incorporated into the membrane of a mammalian cell. The incorporated receptor is functionally equivalent to the wild-type receptor, conferring a PDGF-sensitive mitogenic response on cells lacking the receptor. The construct can be used for enhancing PDGF response of cells, determining the regions involved in transducing the signal in response to PDGF binding, providing mutated analogs and evaluating drugs for their physiologic activity.

摘要翻译： 编码人血小板衍生生长因子受体（hPDGF-R）的DNA序列现已被分离并测序。 包含该序列的表达构建体编码可分泌或并入哺乳动物细胞膜的受体。 所掺入的受体在功能上等同于野生型受体，赋予对缺乏受体的细胞的PDGF敏感的促有丝分裂反应。 该构建体可以用于增强细胞的PDGF应答，确定响应于PDGF结合参与转导信号的区域，提供突变的类似物并评价药物的生理活性。

公开(公告)号：US07105305B2

公开(公告)日：2006-09-12

申请号：US10027400

申请日：2001-12-19

申请人： Lewis T. Williams ,  Jaime A. Escobedo

发明人： Lewis T. Williams ,  Jaime A. Escobedo

IPC分类号： G01N33/53 ,  C07K14/49

CPC分类号： C07K14/71 ,  G01N33/74 ,  G01N2333/49

摘要： DNA sequences encoding human platelet-derived growth factor receptors (hPDGF-R), and expression constructs comprising sequences which encode a receptor that can be secreted or incorporated into the membrane of a mammalian cell. Peptide fragments with functions equivalent to the wild-type receptor, conferring a PDGF-sensitive mitogenic response on cells lacking the receptor are provided. The constructs can be used for enhancing PDGF response of cells, determining the regions involved in transducing the signal in response to PDGF binding, providing mutated analogs and evaluating drugs for their physiologic activity. Soluble fragments comprising PDGF receptor sequences are also provided, including important intracellular kinase insert sequences which interact with intracellular proteins.

公开(公告)号：US06475782B1

公开(公告)日：2002-11-05

申请号：US08451693

申请日：1995-05-26

申请人： Jaime A. Escobedo ,  Lewis T. Williams

发明人： Jaime A. Escobedo ,  Lewis T. Williams

IPC分类号： C12N510

CPC分类号： C07K14/71

摘要： A DNA sequence encoding human platelet-derived growth factor receptor (hPDGF-R) has now been isolated and sequenced. An expression construct comprising the sequence encodes a receptor that can be secreted or incorporated into the membrane of a mammalian cell. The incorporated receptor is functionally equivalent to the wild-type receptor, conferring a PDGF-sensitive mitogenic response on cells lacking the receptor. The construct can be used for enhancing PDGF response of cells, determining the regions involved in transducing the signal in response to PDGF binding, providing mutated analogs and evaluating drugs for their physiologic activity.

摘要翻译： 编码人血小板衍生生长因子受体（hPDGF-R）的DNA序列现已被分离并测序。 包含该序列的表达构建体编码可分泌或并入哺乳动物细胞膜的受体。 所掺入的受体在功能上等同于野生型受体，赋予对缺乏受体的细胞的PDGF敏感的促有丝分裂反应。 该构建体可以用于增强细胞的PDGF应答，确定响应于PDGF结合参与转导信号的区域，提供突变的类似物并评价药物的生理活性。

公开(公告)号：US20120183477A1

公开(公告)日：2012-07-19

申请号：US13378318

申请日：2010-06-25

申请人： Lewis T. Williams ,  Justin Wong ,  Hongbing Zhang

发明人： Lewis T. Williams ,  Justin Wong ,  Hongbing Zhang

IPC分类号： A61K49/00

CPC分类号： A61K49/0008 ,  A61K2039/505 ,  C07K16/00 ,  C07K16/32 ,  C12N15/85 ,  C12N2800/30 ,  C12N2800/80 ,  C12N2840/20 ,  G01N33/5088 ,  G01N2500/10 ,  G01N2800/52

摘要： An in vivo method of validating a candidate therapeutic target molecule is provided. An in vivo method of selecting a therapeutic antibody to a specific target molecule is also provided.

摘要翻译： 提供了验证候选治疗靶分子的体内方法。 还提供了选择特定靶分子的治疗性抗体的体内方法。

公开(公告)号：US07982014B2

公开(公告)日：2011-07-19

申请号：US12652720

申请日：2010-01-05

申请人： Lewis T. Williams ,  Elizabeth Bosch ,  Stephen Doberstein ,  Kevin Hestir ,  Diane Hollenbaugh ,  Ernestine Lee ,  Minmin Qin ,  Ali Sadra ,  Justin Wong ,  Ge Wu ,  Hongbing Zhang

发明人： Lewis T. Williams ,  Elizabeth Bosch ,  Stephen Doberstein ,  Kevin Hestir ,  Diane Hollenbaugh ,  Ernestine Lee ,  Minmin Qin ,  Ali Sadra ,  Justin Wong ,  Ge Wu ,  Hongbing Zhang

IPC分类号： A61K38/00 ,  A61K38/18 ,  A61K39/00

CPC分类号： C07K14/71 ,  A61K45/06 ,  C07K14/765 ,  C07K16/2863 ,  C07K17/08 ,  C07K2319/30 ,  C07K2319/32

摘要： The invention provides FGFR fusion proteins, methods of making them, and methods of using them to treat proliferative disorders, including cancers and disorders of angiogenesis. The FGFR fusion molecules can be made in CHO cells and may comprise deletion mutations in the extracellular domains of the FGFRs which improve their stability. These fusion proteins inhibit the growth and viability of cancer cells in vitro and in vivo. The combination of the relatively high affinity of these receptors for their ligand FGFs and the demonstrated ability of these decoy receptors to inhibit tumor growth is an indication of the clinical value of the compositions and methods provided herein.

摘要翻译： 本发明提供了FGFR融合蛋白，其制备方法以及使用它们来治疗增殖性疾病（包括癌症和血管生成障碍）的方法。 FGFR融合分子可以在CHO细胞中制备，并且可以包含改善其稳定性的FGFRs的细胞外结构域中的缺失突变。 这些融合蛋白体外和体内抑制癌细胞的生长和活力。 这些受体对其配体FGF的相对高亲和力的组合以及这些诱饵受体抑制肿瘤生长的证明的能力是本文提供的组合物和方法的临床价值的指示。

公开(公告)号：US20090286954A1

公开(公告)日：2009-11-19

申请号：US12424373

申请日：2009-04-15

申请人： Lewis T. Williams ,  Keting Chu ,  Ernestine Lee ,  Kevin Hestir ,  Justin Wong ,  Stephen K. Doberstein

发明人： Lewis T. Williams ,  Keting Chu ,  Ernestine Lee ,  Kevin Hestir ,  Justin Wong ,  Stephen K. Doberstein

IPC分类号： C07K14/00 ,  C07K14/765 ,  C07K16/00

CPC分类号： C07K14/47 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A61K38/00 ,  A61K39/00 ,  A61K48/00 ,  C07K14/705

摘要： The invention provides novel human full-length cDNA clones, novel polynucleotides, related polypeptides, related nucleic acid and polypeptide compositions, and related modulators, such as antibodies and small molecule modulators. The invention also provides methods to make and use these cDNA clones, polynucleotides, polypeptides, related compositions, and modulators. These methods include diagnostic, prophylactic and therapeutic applications. The compositions and methods of the invention are useful in treating proliferative disorders, e.g., cancers, and inflammatory, immune, bacterial, and viral disorders.

摘要翻译： 本发明提供新型人全长cDNA克隆，新型多核苷酸，相关多肽，相关核酸和多肽组合物以及相关调节剂，例如抗体和小分子调节剂。 本发明还提供了制备和使用这些cDNA克隆，多核苷酸，多肽，相关组合物和调节剂的方法。 这些方法包括诊断，预防和治疗应用。 本发明的组合物和方法可用于治疗增殖性疾病，例如癌症，炎症，免疫，细菌和病毒性疾病。

公开(公告)号：US06613956B1

公开(公告)日：2003-09-02

申请号：US08832571

申请日：1997-04-02

申请人： Anke Klippel ,  W. Michael Kavanaugh ,  Stephen D. Harrison ,  Lewis T. Williams

发明人： Anke Klippel ,  W. Michael Kavanaugh ,  Stephen D. Harrison ,  Lewis T. Williams

IPC分类号： G01N3300

CPC分类号： C12N9/1205 ,  A01K67/0339 ,  A01K2217/05 ,  A61K48/00 ,  C07K2319/00 ,  C12P9/00 ,  C12P19/44

摘要： Polynucleotide constructs encoding growth factor independent catalytically active membrane targeted PI 3-kinase mutants useful for therapeutic and research purposes are described. In addition, a method for using the polynucleotide constructs to screen for inhibitors of PI 3-kinase, a method for making 3′ phosphorylated inositol phospholipids, methods of reducing cell death after trauma, and methods of overcoming insulin resistance are described.

摘要翻译： 描述了用于治疗和研究目的的编码不依赖于生长因子的催化活性膜靶向PI3-激酶突变体的多核苷酸构建体。 此外，描述了使用多核苷酸构建体筛选PI 3激酶抑制剂的方法，制备3'磷酸化肌醇磷脂的方法，减少创伤后细胞死亡的方法以及克服胰岛素抵抗的方法。

公开(公告)号：US06432668B1

公开(公告)日：2002-08-13

申请号：US09206344

申请日：1998-12-07

申请人： Christoph Reinhard ,  David Pot ,  Altaf Kassam ,  Tasha Marenbach ,  Lewis T. Williams

发明人： Christoph Reinhard ,  David Pot ,  Altaf Kassam ,  Tasha Marenbach ,  Lewis T. Williams

IPC分类号： C12P2106

CPC分类号： C12N9/1205 ,  A61K38/00 ,  C07K2319/00 ,  C12Y207/11022 ,  Y02A90/24 ,  Y02A90/26

摘要： A human gene encoding a novel cyclin-dependent kinase termed hPFTAIRE and its expression products can be used to provide reagents and methods for detecting migrating or metastasizing cells. Compositions and methods for treating proliferative disorders and neoplasia are also provided.

摘要翻译： 编码称为hPFTAIRE的新型细胞周期蛋白依赖性激酶的人基因及其表达产物可用于提供用于检测迁移或转移细胞的试剂和方法。 还提供了治疗增殖性疾病和瘤形成的组合物和方法。

公开(公告)号：US06355440B1

公开(公告)日：2002-03-12

申请号：US08459082

申请日：1995-06-02

申请人： Lewis T. Williams ,  Daniel F. Johnson ,  Pauline E Lee

发明人： Lewis T. Williams ,  Daniel F. Johnson ,  Pauline E Lee

IPC分类号： G01N3353

CPC分类号： C07K14/71 ,  A61K38/00 ,  G01N33/74 ,  G01N2333/50 ,  G01N2333/71 ,  G01N2500/00

摘要： The present invention relates to receptors for growth factors, specifically to the fibroblast growth factor receptor (FGF-R). More particularly, it provides various purified fibroblast growth factor receptor proteins, nucleic acids encoding the receptor proteins, methods for the production of purified FGF-R proteins, proteins made by these methods, antibodies against these proteins, diagnostic and therapeutic uses of these various reagents, and methods of detecting a fibroblast growth factor in a sample using the disclosed fibroblast growth factor receptors.

摘要翻译： 本发明涉及生长因子受体，特别涉及成纤维细胞生长因子受体（FGF-R）。 更具体地，其提供各种纯化的成纤维细胞生长因子受体蛋白质，编码受体蛋白质的核酸，用于产生纯化的FGF-R蛋白质的方法，通过这些方法制备的蛋白质，针对这些蛋白质的抗体，这些各种试剂的诊断和治疗用途 以及使用所公开的成纤维细胞生长因子受体检测样品中成纤维细胞生长因子的方法。