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1. 发明申请

US20080112937A1 Method of Producing Autologous Embryonic Stem Cells 审中-公开
标题翻译：生产自体胚胎干细胞的方法
公开(公告)号：US20080112937A1
公开(公告)日：2008-05-15
申请号：US11632860
申请日：2005-07-19
申请人： Lewis T Williams , Hongbing Zhang , Srinivas Kothakota , Kristen Pierce , Pierre Alvaro Beaurang , Keting Chu
发明人： Lewis T Williams , Hongbing Zhang , Srinivas Kothakota , Kristen Pierce , Pierre Alvaro Beaurang , Keting Chu
IPC分类号： A61K48/00 , C12N5/08 , C12N15/09
CPC分类号： C12N5/0606 , A01K2217/05 , C12N15/873 , C12N2506/00
摘要： Aspects of the present invention relate to compositions and methods of reprogramming a somatic cell to give rise to an autologous embryonic stem cell. These methods involve providing a somatic cell of a donor subject, introducing the somatic cell into an embryo of a recipient subject to produce a chimeric embryo, allowing the chimeric embryo to develop further wherein the somatic cell will reprogram, and then selecting an autologous embryonic stem cell that has developed from the somatic cell. The methods and composition of producing pluripotent embryonic stem cells from a donor's own somatic cells invite the possibility of a number of therapeutic applications, including organ transplant and treatment of autoimmune diseases, cancer, and degenerative disorders such as diabetes, Alzheimer's, and Parkinson's.
摘要翻译：本发明的方面涉及重编程体细胞以产生自体胚胎干细胞的组合物和方法。这些方法涉及提供供体受试者的体细胞，将体细胞引入受体的胚胎以产生嵌合胚胎，允许嵌合胚胎进一步发育，其中体细胞将重新编程，然后选择自体胚胎干从体细胞发育而来的细胞。从供体自身体细胞细胞产生多能胚胎干细胞的方法和组成可引起许多治疗应用的可能性，包括器官移植和治疗自身免疫性疾病，癌症和退行性疾病如糖尿病，阿尔茨海默病和帕金森病。

2. 发明申请

US20080254033A1 Pharmaceutical Compositions Containing Antagonists to Lrp4, Lrp8 or Megalin for Treatment of Diseases 审中-公开
标题翻译：含有Lrp4，Lrp8或Megalin拮抗剂的药物组合物用于治疗疾病
公开(公告)号：US20080254033A1
公开(公告)日：2008-10-16
申请号：US10586669
申请日：2005-01-21
申请人： Kristen Pierce , Amy L.Tsui Collins , Hongbing Zhang , Lewis Thomas Williams , Pierre Alvaro Beaurang
发明人： Kristen Pierce , Amy L.Tsui Collins , Hongbing Zhang , Lewis Thomas Williams , Pierre Alvaro Beaurang
IPC分类号： A61K39/395 , A61P25/28 , C07K14/435 , C12N15/85 , C07K16/00 , C12N5/10 , C12N15/12 , A61K31/7105
CPC分类号： C07K14/705
摘要： The present invention provides LRP4, LRP8 and LRP2 (megalin) polypeptides; polynucleotides encoding such; modulators of LRP4, LRP8 and LRP2 activity; and pharmaceutical compositions for the treatment of diseases. Compositions of the invention contain a pharmaceutically acceptable carrier or excipient and at least one modulator that is capable of binding to or interfering with the activity of LRP4, LRP8, LRP2 and active fragments thereof. The invention provides modulators, such as antibodies, RNAi molecules, anti-sense molecules and ribozymes. Additionally, the invention includes methods for the treatment of diseases, such as proliferative diseases and degenerative diseases, and methods of administration of the compositions of the invention.
摘要翻译：本发明提供LRP4，LRP8和LRP2（巨蛋白）多肽; 编码这样的多核苷酸; LRP4，LRP8和LRP2活性的调节剂; 和用于治疗疾病的药物组合物。本发明的组合物含有药学上可接受的载体或赋形剂和至少一种能够结合或干扰LRP4，LRP8，LRP2及其活性片段的活性的调节剂。本发明提供了调节剂，例如抗体，RNAi分子，反义分子和核酶。另外，本发明包括治疗疾病如增殖性疾病和退行性疾病的方法，以及本发明组合物的施用方法。

3. 发明申请

US20060035373A1 Stem cell libraries 审中-公开
标题翻译：干细胞库
公开(公告)号：US20060035373A1
公开(公告)日：2006-02-16
申请号：US11003840
申请日：2004-12-06
申请人： Hongbing Zhang , Lewis Williams , Keting Chu , Fred Cohen
发明人： Hongbing Zhang , Lewis Williams , Keting Chu , Fred Cohen
IPC分类号： C12N5/08 , C12N15/87 , C40B40/02
CPC分类号： C12N5/0606
摘要： A stem cell library is created by genetically modifying stem cells with nucleic acids encoding polypeptides which can promote stem cell differentiation into specific cell types. Alternatively, the stem cell library is exposed to an externally added factor that promotes stem cell differentiation into a desired cell line, e.g., neuronal or muscle. The library is used to determine the effect of the encoded protein on the differentiation process. The library is also used to produce nucleic acids for insertion into embryonic stem cells to produce transfected embryonic stem cells. The nucleic acids are inserted into a locus that permits widespread expression of the encoded polypeptide in animals produced from blastocysts that incorporate the transfected cells. Non-human chimeric animals produced by combining blastocysts derived from animal models of human disease and embryonic stem cells transfected with molecules from the library provide an in vivo system for therapeutic design.
摘要翻译：通过用能够促进干细胞分化成特定细胞类型的多肽的核酸对遗传修饰干细胞产生干细胞文库。或者，干细胞文库暴露于促进干细胞分化成所需细胞系（例如神经元或肌肉）的外部添加因子。该文库用于确定编码的蛋白质对分化过程的影响。该文库还用于生产用于插入胚胎干细胞以产生转染的胚胎干细胞的核酸。将核酸插入到允许编码的多肽在掺入转染细胞的囊胚产生的动物中广泛表达的基因座。通过将源自人类疾病的动物模型的胚泡和来自文库的分子转染的胚胎干细胞组合产生的非人类嵌合动物提供用于治疗设计的体内系统。

4. 发明申请

US20050244970A1 Stem cell libraries 审中-公开
标题翻译：干细胞库
公开(公告)号：US20050244970A1
公开(公告)日：2005-11-03
申请号：US10516605
申请日：2003-10-31
申请人： Hongbing Zhang , Lewis Williams , Keting Chu
发明人： Hongbing Zhang , Lewis Williams , Keting Chu
IPC分类号： A01K67/00 , A01K67/033 , C12N20060101 , C12N5/00 , C12N5/02 , C12N5/0735 , C12N15/85 , G01N33/00 , C12N5/08
CPC分类号： C12N5/0606
摘要： A stem cell library is created by genetically modifying stem cells with nucleic acids encoding polypeptides which can promote stem cell differentiation into specific cell types. Alternatively, the stem cell library is exposed to an externally added factor that promotes stem cell differentiation into a desired cell line, e.g., neuronal or muscle. The library is used to determine the effect of the encoded protein on the differentiation process. The library is also used to produce nucleic acids for insertion into embryonic stem cells to produce transfected embryonic stem cells. The nucleic acids are inserted into a locus that permits widespread expression of the encoded polypeptide in animals produced from blastocysts that incorporate the transfected cells. Non-human chimeric animals produced by combining blastocysts derived from animal models of human disease and embryonic stem cells transfected with molecules from the library provide an in vivo system for therapeutic design.
摘要翻译：通过用能够促进干细胞分化成特定细胞类型的多肽的核酸对遗传修饰干细胞产生干细胞文库。或者，将干细胞文库暴露于外部添加的因子，其促进干细胞分化成期望的细胞系，例如神经元或肌肉。该文库用于确定编码的蛋白质对分化过程的影响。该文库还用于生产用于插入胚胎干细胞以产生转染的胚胎干细胞的核酸。将核酸插入到允许编码的多肽在掺入转染细胞的囊胚产生的动物中广泛表达的基因座。通过将源自人类疾病的动物模型的胚泡和来自文库的分子转染的胚胎干细胞组合产生的非人类嵌合动物提供用于治疗设计的体内系统。

5. 发明申请

US20100158911A1 Compositions and Methods of Treating Disease with FGFR Fusion Proteins 有权
标题翻译：用FGFR融合蛋白治疗疾病的组合物和方法
公开(公告)号：US20100158911A1
公开(公告)日：2010-06-24
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： A61K39/395 , C07K19/00 , C07K14/00 , C07H21/04 , A61K38/16 , A61P35/00 , A61P35/04 , C12N5/10 , C12P21/06 , C12N15/63 , G01N33/53
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。

6. 发明申请

US20120183477A1 Therapeutic Antibody Target Validation and Screening In Vivo 审中-公开
标题翻译：治疗性抗体目标验证和筛选体内
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。

7. 发明授权

US07982014B2 FGFR3-IIIc fusion proteins 有权
标题翻译： FGFR3-IIIc融合蛋白
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。

8. 发明申请

US20130065276A1 COMPOSITIONS AND METHODS OF TREATING DISEASE WITH FGFR FUSION PROTEINS 有权
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.

9. 发明申请

US20110281302A1 COMPOSITIONS AND METHODS OF TREATING DISEASE WITH FGFR FUSION PROTEINS 有权
标题翻译：用FGFR融合蛋白治疗疾病的组合物和方法
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。

10. 发明申请

US20120301921A1 COMPOSITIONS AND METHODS OF TREATING DISEASE WITH FGFR FUSION PROTEINS 有权
标题翻译：用FGFR融合蛋白治疗疾病的组合物和方法
公开(公告)号：US20120301921A1
公开(公告)日：2012-11-29
申请号：US13438638
申请日：2012-04-03
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： C07K14/50 , C12P21/00 , C12N15/85 , C12N5/10 , C07K19/00 , C12N15/16
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。

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