公开(公告)号：US08580936B2

公开(公告)日：2013-11-12

申请号：US13227398

申请日：2011-09-07

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： C07H21/04 ,  A61K39/00 ,  C12P21/02 ,  C12N5/10 ,  C12N15/00

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：US20090214517A1

公开(公告)日：2009-08-27

申请号：US11658412

申请日：2005-07-27

申请人： Justin Wong ,  Kevin Hestir ,  Ernestine Lee

发明人： Justin Wong ,  Kevin Hestir ,  Ernestine Lee

IPC分类号： A61K39/395 ,  A61P35/00

CPC分类号： C07K14/4703

摘要： Microarray analysis, confirmed by RT-PCT, demonstrated that mRNA derived from cancerous tissues hybridized specifically and preferentially to human nectin 4, semaphorin 4b, IgSF9, and KIAA0152. Microarray analysis also demonstrated that RNA from malignant bladder, pancreas, and stomach tissue hybridized specifically to human nectin 4, semaphorin 4b, IgSF9, and KIAA0152, all of which are transmembrane proteins that provide a therapeutic target for treating cancer. Modulators of nectin 4, semaphorin 4b, IgSF9, and KIAA0152 are provided for the diagnosis and treatment of proliferative disorders such as cancer and psoriasis. The invention further provides methods of treating cancer with therapeutic agents directed toward nectin 4, semaphorin 4b, IgSF9, and KIAA0152.

摘要翻译： 通过RT-PCT证实的微阵列分析表明，衍生自癌组织的mRNA特异性地优先与人Nectin 4，信号素4b，IgSF9和KIAA0152杂交。 微阵列分析还表明，来自恶性膀胱，胰腺和胃组织的RNA与人Nectin 4，信号素4b，IgSF9和KIAA0152特异性杂交，所有这些都是提供治疗癌症治疗靶标的跨膜蛋白。 提供了Nectin 4，semaphorin 4b，IgSF9和KIAA0152的调节剂用于诊断和治疗增殖性疾病如癌症和牛皮癣。 本发明还提供了针对nectin 4，semaphorin 4b，IgSF9和KIAA0152的治疗剂治疗癌症的方法。

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：US20100324270A1

公开(公告)日：2010-12-23

申请号：US12279703

申请日：2007-02-20

申请人： Kevin Hestir ,  Justin Wong

发明人： Kevin Hestir ,  Justin Wong

IPC分类号： C07K16/18

CPC分类号： C07K14/47 ,  A61K38/00

摘要： This invention relates to the polynucleotides and the encoded polypeptides, including novel sequences, of human or non-human primate genes that are amplified in breast and/or other tumor tissues melanoma, as compared to the corresponding normal tissue. The invention also relates to modulators of such polynucleotides and polypeptides, for example, antibodies, that specifically bind to and/or interfere with the activity of this polypeptide, polynucleotide, its fragments, variants, and antagonists. The invention further relates to compositions containing such a polypeptide, polynucleotide, or modulators thereof and uses of such compositions in methods of treating or preventing cancer, by detecting this polynucleotide, polypeptide, or antibodies thereto in patient samples. The invention also provides diagnostic tests for breast cancer and melanoma, by identifying polypeptides and polynucleotides encoded by the cDNA sequence of the invention that correlate with those disorders.

摘要翻译： 本发明涉及与相应的正常组织相比，在乳腺和/或其它肿瘤组织黑素瘤中扩增的人或非人灵长类动物基因的多核苷酸和编码多肽，包括新序列。 本发明还涉及这种多核苷酸和多肽的调节剂，例如抗体，其特异性结合和/或干扰该多肽，多核苷酸，其片段，变体和拮抗剂的活性。 本发明进一步涉及通过在患者样品中检测该多核苷酸，多肽或其抗体，含有此类多肽，多核苷酸或其调节剂的组合物以及在治疗或预防癌症的方法中的用途。 本发明还通过鉴定与本发明的cDNA序列编码的多肽和与这些疾病相关的多核苷酸来提供对乳腺癌和黑素瘤的诊断测试。

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：US20070264277A1

公开(公告)日：2007-11-15

申请号：US11632319

申请日：2005-07-21

申请人： Dirk Behrens ,  Elizabeth Bosch ,  Stephen Doberstein ,  Robert Halenbeck ,  Kevin Hestir ,  Min Huang ,  Ernestine Lee ,  Haishan Lin ,  Thomas Linnemann ,  Shannon Marshall ,  Justin Wong ,  Ge Wu ,  Aileen Zhou

发明人： Dirk Behrens ,  Elizabeth Bosch ,  Stephen Doberstein ,  Robert Halenbeck ,  Kevin Hestir ,  Min Huang ,  Ernestine Lee ,  Haishan Lin ,  Thomas Linnemann ,  Shannon Marshall ,  Justin Wong ,  Ge Wu ,  Aileen Zhou

IPC分类号： A61K39/00 ,  A61K38/00 ,  C07H21/00 ,  C07K14/00 ,  C07K16/18 ,  C12N15/00 ,  C12N15/87 ,  C12N5/06 ,  C12P1/00 ,  G01N33/53

CPC分类号： C07K16/243 ,  A61K38/00 ,  C07K14/53

摘要： 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.

摘要翻译： 公开了一种新鉴定的分泌型分子，本文称为“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。

公开(公告)号：US20060084799A1

公开(公告)日：2006-04-20

申请号：US10948571

申请日：2004-09-24

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

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

IPC分类号： C07K14/705 ,  A01K67/00 ,  C07H21/04 ,  C12P21/06 ,  C12N5/06

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：US20130065276A1

公开(公告)日：2013-03-14

申请号：US13227398

申请日：2011-09-07

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： C12P21/00 ,  C12N5/073 ,  C12N5/07 ,  C12N15/13 ,  C12N15/85

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.

公开(公告)号：US20110281302A1

公开(公告)日：2011-11-17

申请号：US13157712

申请日：2011-06-10

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： C12P21/04 ,  C12N5/10 ,  C07H21/04 ,  C07K14/00 ,  C07K16/46

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：US20100028867A1

公开(公告)日：2010-02-04

申请号：US12084172

申请日：2006-10-25

申请人： Elizabeth Bosch ,  Kevin Hestir ,  Justin Wong

发明人： Elizabeth Bosch ,  Kevin Hestir ,  Justin Wong

IPC分类号： C12Q1/68 ,  G01N33/574

CPC分类号： C07K14/705 ,  A61K38/00

摘要： Microarray analysis, confirmed by RT-PCR, demonstrated that mRNA from certain cancer tissues, for example, ovarian cancer tissue, pancreatic cancer tissue, and colorectal cancer tissue, hybridizes specifically and preferentially to LRRTM1. LRRTM1 is a leucine-rich repeat transmembrane protein overexpressed on the surface of cancer cells compared to normal tissues and thus provides a therapeutic target for treating cancer. Modulators of LRRTM1, highly expressed in cancerous as compared to normal tissues, are provided for the diagnosis and treatment of proliferative disorders such as cancer. The invention further provides methods of treating cancer with therapeutic agents directed toward LRRTM1.

摘要翻译： 通过RT-PCR证实的微阵列分析表明，来自某些癌症组织例如卵巢癌组织，胰腺癌组织和结肠直肠癌组织的mRNA与LRRTM1具体和优先地杂交。 与正常组织相比，LRRTM1是在癌细胞表面上过表达的富含亮氨酸的重复跨膜蛋白，因此提供了治疗癌症的治疗靶点。 提供了与正常组织相比在癌症中高度表达的LRRTM1的调节剂用于诊断和治疗增殖性疾病如癌症。 本发明还提供了针对LRRTM1的治疗剂治疗癌症的方法。