公开(公告)号：US6165733A

公开(公告)日：2000-12-26

申请号：US861745

申请日：1997-05-22

Applicant: Hui Cen ,  Lewis T. Williams

Inventor： Hui Cen ,  Lewis T. Williams

IPC: C07K14/47 ,  C12N9/12 ,  C12N15/12 ,  C12Q1/00 ,  C07K14/46 ,  C12N15/62

CPC classification number: C12N9/1205 ,  C07K14/47 ,  C07K2319/00

Abstract: A mammalian protein involved in receptor-mediated endocytosis specifically binds to phosphatidylinositol 3-kinase. More specifically it binds to the Bcr homology domain of the p85 subunit of phosphatidylinositol 3-kinase. Phathoidylinositol 3-kinase also binds to platelet derived growth factor receptor. Other receptors may also bind, including those for insulin, insulin-like growth factor-1, colony stimulating factor 1, nerve growth factor, hepatocyte growth factor, stem cell growth factor, and epidermal growth factor. Mitogenesis is the consequence of the binding and internalization of these growth factors. Inhibition of the process of receptor-mediated internalization inhibits mitogenesis.

Abstract translation: 参与受体介导的内吞作用的哺乳动物蛋白质特异性结合磷脂酰肌醇3-激酶。 更具体地说，它结合磷脂酰肌醇3-激酶的p85亚基的Bcr同源结构域。 Phathoidylinositol 3-kinase也与血小板衍生生长因子受体结合。 其他受体也可能结合，包括胰岛素，胰岛素样生长因子-1，集落刺激因子1，神经生长因子，肝细胞生长因子，干细胞生长因子和表皮生长因子。 有丝分裂是这些生长因子的结合和内化的结果。 受体介导的内化过程的抑制抑制有丝分裂。

公开(公告)号：US20120183477A1

公开(公告)日：2012-07-19

申请号：US13378318

申请日：2010-06-25

Applicant: Lewis T. Williams ,  Justin Wong ,  Hongbing Zhang

Inventor： Lewis T. Williams ,  Justin Wong ,  Hongbing Zhang

IPC: A61K49/00

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

Abstract: 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.

Abstract translation: 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

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

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

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

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

Abstract: 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.

Abstract translation: 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

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

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

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

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

Abstract: 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.

Abstract translation: 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

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

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

IPC: G01N3300

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

Abstract: 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.

Abstract translation: 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

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

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

IPC: C12P2106

CPC classification number: C12N9/1205 ,  A61K38/00 ,  C07K2319/00 ,  C12Y207/11022 ,  Y02A90/24 ,  Y02A90/26

Abstract: 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.

Abstract translation: 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

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

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

IPC: G01N3353

CPC classification number: C07K14/71 ,  A61K38/00 ,  G01N33/74 ,  G01N2333/50 ,  G01N2333/71 ,  G01N2500/00

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US5948664A

公开(公告)日：1999-09-07

申请号：US609049

申请日：1996-02-12

Applicant: Lewis T. Williams ,  Lisa Molz ,  Yen-Wen Chen

Inventor： Lewis T. Williams ,  Lisa Molz ,  Yen-Wen Chen

IPC: A61K38/00 ,  C12N9/12

CPC classification number: C12N9/1205 ,  A61K38/00

Abstract: The present invention generally provides polypeptides that are related to and/or derived from the family of PI3-kinases. These polypeptides are generally involved in cell signaling cascades which control, e.g., cell cycle progression and intracellular protein sorting. The family of PI3-kinases from which the polypeptides of the invention are derived are generally characterized by their structure as well as their unique substrate specificity.

Abstract translation: 本发明通常提供与PI3-激酶家族有关和/或衍生自PI3-激酶家族的多肽。 这些多肽通常参与控制例如细胞周期进程和细胞内蛋白质分选的细胞信号传导级联。 得自本发明多肽的PI3-激酶家族通常以其结构以及它们独特的底物特异性为特征。

公开(公告)号：US5707632A

公开(公告)日：1998-01-13

申请号：US458938

申请日：1995-06-02

Applicant: Lewis T. Williams ,  Daniel E. Johnson ,  Pauline E. Lee

Inventor： Lewis T. Williams ,  Daniel E. Johnson ,  Pauline E. Lee

IPC: A61K38/00 ,  A01N20060101 ,  A61K38/04 ,  A61P35/00 ,  A61P43/00 ,  C07K14/00 ,  C07K14/47 ,  C07K14/705 ,  C07K14/71 ,  C07K14/715 ,  C07K16/28 ,  C12N5/10 ,  C12N15/09 ,  C12N15/12 ,  C12P20060101 ,  C12P21/02 ,  C12P21/08 ,  C12Q1/00 ,  C12R1/91 ,  G01N33/53 ,  G01N33/577 ,  G01N33/74 ,  C07K1/00 ,  C07K16/00

CPC classification number: C07K14/71 ,  G01N33/74 ,  A61K38/00 ,  G01N2333/50 ,  G01N2333/71 ,  G01N2500/00

Abstract: A fibroblast growth factor (FGF) receptor including a basic fibroblast growth factor receptor has been purified. Various forms have been identified including soluble forms lacking any transmembrane segment. DNA sequences encoding full-length fibroblast growth factor receptors and polypeptides comprising a portion of an FGF-R ligand-binding domain have been isolated and sequenced. These DNAs include DNAs encoding for a basic FGF-R and a human FGF-R and are operably linked to control sequences and expressed in a culture of a compatible host transformed, transfected or electrophoresed by a cloning vehicle containing the DNA sequence. The invention also comprises antibodies to the receptor, methods of synthesizing the growth factor receptor proteins, methods for providing analogs of the fibroblast growth factor receptors. Methods for evaluating compositions which promote or inhibit fibroblastic growth factors and compositions which are agonistic or antagonistic to fibroblast growth factor receptors are also provided. Diagnostic and therapeutic uses are described.

Abstract translation: 已经纯化了包含碱性成纤维细胞生长因子受体的成纤维细胞生长因子（FGF）受体。 已经鉴定了各种形式，包括不含任何跨膜片段的可溶形式。 已经分离并测序了编码全长成纤维细胞生长因子受体的DNA序列和包含一部分FGF-R配体结合结构域的多肽。 这些DNA包括编码碱性FGF-R和人FGF-R的DNA，并且与对照序列可操作地连接，并在通过含有DNA序列的克隆载体转化，转染或电泳的相容宿主的培养物中表达。 本发明还包括对受体的抗体，合成生长因子受体蛋白质的方法，提供成纤维细胞生长因子受体类似物的方法。 还提供了评估促进或抑制成纤维细胞生长因子的组合物和对成纤维细胞生长因子受体具有激动作用或拮抗作用的组合物的方法。 描述诊断和治疗用途。

公开(公告)号：US20120258071A1

公开(公告)日：2012-10-11

申请号：US13446254

申请日：2012-04-13

Applicant: Dirk Behrens ,  Elizabeth Bosch ,  Stephen K. Doberstein ,  Robert Forgan Halenbeck ,  Kevin Hestir ,  Min Mei Huang ,  Ernestine Lee ,  Haishan Lin ,  Thomas Linnemann ,  Shannon Marshall ,  Justin G. P. Wong ,  Ge Wu ,  Aileen Zhou ,  Cindy Leo ,  Lewis T. Williams

Inventor： Dirk Behrens ,  Elizabeth Bosch ,  Stephen K. Doberstein ,  Robert Forgan Halenbeck ,  Kevin Hestir ,  Min Mei Huang ,  Ernestine Lee ,  Haishan Lin ,  Thomas Linnemann ,  Shannon Marshall ,  Justin G. P. Wong ,  Ge Wu ,  Aileen Zhou ,  Cindy Leo ,  Lewis T. Williams

IPC: A61K38/19 ,  C07K17/02 ,  A61P35/00 ,  A61P37/00 ,  A61P31/00 ,  C07K17/00 ,  C07K19/00

CPC classification number: C07K16/243 ,  A61K38/00 ,  C07K14/53

Abstract: Disclosed is a newly identified secreted molecule, identified herein as “monocyte, granulocyte, and dendritic cell colony stimulating factor” (MGD-CSF), the polypeptide sequence, and polynucleotides encoding the polypeptide sequence. Also provided is a procedure for producing the polypeptide by recombinant techniques employing, for example, vectors and host cells. Additionally, procedures are described to modify the disclosed novel molecules of the invention to prepare fusion molecules. Also disclosed are methods for using the polypeptides and active fragments thereof for treatment of a variety of diseases, including, for example, cancer, autoimmune and inflammatory diseases, infectious diseases, and recurrent pregnancy loss.

Abstract translation: 公开了一种新鉴定的分泌型分子，本文鉴定为单核细胞，粒细胞和树突细胞集落刺激因子（MGD-CSF），多肽序列和编码多肽序列的多核苷酸。 还提供了通过使用例如载体和宿主细胞的重组技术产生多肽的方法。 另外，描述了修饰所公开的本发明新颖分子以制备融合分子的方法。 还公开了将多肽及其活性片段用于治疗各种疾病（包括例如癌症，自身免疫性和炎性疾病，感染性疾病和复发性妊娠损失）的方法。