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1.发明申请公开(公告)号：US20090221594A1
公开(公告)日：2009-09-03
申请号：US12095458
申请日：2006-11-30
申请人： Andrew X. Chen , Hongjie Wu , Mark J. Cantwell , Joan M. Robbins
发明人： Andrew X. Chen , Hongjie Wu , Mark J. Cantwell , Joan M. Robbins
IPC分类号： A61K31/4985
CPC分类号： A61K31/525 , A61K9/19
摘要： The invention provides a stable lyophilized composition of 5,10 methylenetetrahydrofolate suitable for use in the treatment of cancer and other therapies. The composition comprises 5,10-MTHF in combination with citric acid and ascorbic acid, with the ratio of citric acid to ascorbic acid from about 0.75:1 to about 2.25:1 by weight, and the ratio of total citric acid and ascorbic acid to 5,10-MTHF from about 1.4:1 to about 3.4:1 by weight. Prior to lyophilization, the solution is adjusted to an essentially neutral pH.
摘要翻译： 本发明提供了适合用于治疗癌症和其它疗法的5,10亚甲基四氢叶酸的稳定的冻干组合物。 该组合物包含与柠檬酸和抗坏血酸组合的5,10-MTHF，柠檬酸与抗坏血酸的比例为约0.75:1至约2.25:1，总柠檬酸与抗坏血酸的比例与 5,10-MTHF为约1.4:1至约3.4:1重量比。 在冻干之前，将溶液调节至基本上中性的pH。
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公开(公告)号：US20110177556A1
公开(公告)日：2011-07-21
申请号：US13074638
申请日：2011-03-29
CPC分类号： C07K14/70575
摘要： The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.
摘要翻译： 本发明提供了编码嵌合CD154的分离的多核苷酸序列，其包含编码非人CD154，优选小鼠CD154的细胞外亚结构域的第一核苷酸序列，其替代人CD154的切割位点，以及编码细胞外的第二核苷酸序列 结合人CD154受体的人CD154的亚结构域。 本发明还提供了由上述多核苷酸序列编码的嵌合CD154，表达载体和包含多核苷酸序列的遗传载体，包含表达载体或遗传载体的宿主细胞， CD154，以及用于使用含有嵌合CD154多核苷酸序列的表达载体和遗传构建体的方法。
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3.发明授权Chimeric nucleic acids encoding polypeptides comprising TNF alpha, CD70 and FAS ligand domains 有权编码包含TNFα，CD70和FAS配体结构域的多肽的嵌合核酸公开(公告)号：US07964712B2
公开(公告)日：2011-06-21
申请号：US12871807
申请日：2010-08-30
CPC分类号： C07K14/525 , A61K38/00 , C07K2319/00
摘要： The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNFα, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNFα, wherein the encoded domain or subdomain replaces a cleavage site of native TNFα, and a second nucleotide sequence encoding a domain or subdomain of native TNFα that binds to a TNFα receptor. The encoded chimeric TNFα is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNFα receptor on the surface of a cell. The chimeric TNFα is therefore useful in methods for inducing apoptosis of a cell expressing a TNFα receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNFα that is expressed on the surface of the cell.
摘要翻译： 本发明涉及编码嵌合TNFα的分离的多核苷酸序列，其包含编码除TNFα之外的肿瘤坏死因子配体的结构域或亚结构域的第一核苷酸序列，其中编码的结构域或亚结构域替代天然TNFα的切割位点，以及 编码结合TNFα受体的天然TNFα的结构域或亚结构域的第二核苷酸序列。 编码的嵌合TNFα对细胞表面的切割显着较不敏感，结果可以增加能够结合细胞表面的TNFα受体的配体的浓度。 因此，嵌合TNFα可用于诱导表达TNFα受体的细胞的凋亡，诱导免疫系统细胞的活化和治疗肿瘤细胞的方法，通过将编码嵌合TNFα的分离的多核苷酸序列引入感兴趣的细胞中，所述多核苷酸序列表达于 电池的表面。
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公开(公告)号：US07928213B2
公开(公告)日：2011-04-19
申请号：US12389904
申请日：2009-02-20
CPC分类号： C07K14/70575
摘要： The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.
摘要翻译： 本发明提供了编码嵌合CD154的分离的多核苷酸序列，其包含编码非人CD154，优选小鼠CD154的细胞外亚结构域的第一核苷酸序列，其替代人CD154的切割位点，以及编码细胞外的第二核苷酸序列 结合人CD154受体的人CD154的亚结构域。 本发明还提供了由上述多核苷酸序列编码的嵌合CD154，表达载体和包含多核苷酸序列的遗传载体，包含表达载体或遗传载体的宿主细胞， CD154，以及用于使用含有嵌合CD154多核苷酸序列的表达载体和遗传构建体的方法。
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公开(公告)号：US20110008842A1
公开(公告)日：2011-01-13
申请号：US12871807
申请日：2010-08-30
IPC分类号： C12P21/02 , C07H21/00 , C12N15/63 , C12N15/86 , C12N15/74 , C12N15/861 , C12N15/867 , C12N5/10 , C07K14/00
CPC分类号： C07K14/525 , A61K38/00 , C07K2319/00
摘要： The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNFα, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNFα, wherein the encoded domain or subdomain replaces a cleavage site of native TNFα, and a second nucleotide sequence encoding a domain or subdomain of native TNFα that binds to a TNFα receptor. The encoded chimeric TNFα is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNFα receptor on the surface of a cell. The chimeric TNFα is therefore useful in methods for inducing apoptosis of a cell expressing a TNFα receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNFα that is expressed on the surface of the cell.
摘要翻译： 本发明涉及编码嵌合TNFα的分离的多核苷酸序列，其包含编码除TNFα之外的肿瘤坏死因子配体的结构域或亚结构域的第一核苷酸序列，其中编码的结构域或亚结构域替代天然TNFα的切割位点，以及 编码结合TNFα受体的天然TNFα的结构域或亚结构域的第二核苷酸序列。 编码的嵌合TNFα对细胞表面的切割显着较不敏感，结果可以增加能够结合细胞表面的TNFα受体的配体的浓度。 因此，嵌合TNFα可用于诱导表达TNFα受体的细胞的凋亡，诱导免疫系统细胞的活化和治疗肿瘤细胞的方法，通过将编码嵌合TNFα的分离的多核苷酸序列引入感兴趣的细胞中，所述多核苷酸序列表达于 电池的表面。
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公开(公告)号：US08138310B2
公开(公告)日：2012-03-20
申请号：US13074638
申请日：2011-03-29
IPC分类号： C07K14/705
CPC分类号： C07K14/70575
摘要： The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.
摘要翻译： 本发明提供了编码嵌合CD154的分离的多核苷酸序列，其包含编码非人CD154，优选小鼠CD154的细胞外亚结构域的第一核苷酸序列，其替代人CD154的切割位点，以及编码细胞外的第二核苷酸序列 结合人CD154受体的人CD154的亚结构域。 本发明还提供了由上述多核苷酸序列编码的嵌合CD154，表达载体和包含多核苷酸序列的遗传载体，包含表达载体或遗传载体的宿主细胞， CD154，以及用于使用含有嵌合CD154多核苷酸序列的表达载体和遗传构建体的方法。
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公开(公告)号：US07495090B2
公开(公告)日：2009-02-24
申请号：US10154759
申请日：2002-05-23
CPC分类号： C07K14/70575
摘要： The present invention provides for an isolated polynucleotide sequence encoding a chimeric CD154, comprising a first nucleotide sequence encoding an extracellular subdomain of non-human CD154, preferably murine CD154, that replaces a cleavage site of human CD154, and a second nucleotide sequence encoding an extracellular subdomain of human CD154 that binds to a human CD154 receptor. The present invention also provides for the chimeric CD154 that is encoded by the above-described polynucleotide sequence, an expression vector and a genetic vector comprising the polynucleotide sequence, a host cell comprising the expression vector or the genetic vector, a process for producing the chimeric CD154, and methods for utilizing the expression vectors and genetic constructs containing the chimeric CD154 polynucleotide sequences.
摘要翻译： 本发明提供了编码嵌合CD154的分离的多核苷酸序列，其包含编码非人CD154，优选小鼠CD154的细胞外亚结构域的第一核苷酸序列，其替代人CD154的切割位点，以及编码细胞外的第二核苷酸序列 结合人CD154受体的人CD154的亚结构域。 本发明还提供了由上述多核苷酸序列编码的嵌合CD154，表达载体和包含多核苷酸序列的遗传载体，包含表达载体或遗传载体的宿主细胞， CD154，以及用于使用含有嵌合CD154多核苷酸序列的表达载体和遗传构建体的方法。
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8.发明申请Nucleic Acid Molecules Encoding TNF-Alpha Ligand Polypeptides Having a CD154 Domain 审中-公开编码具有CD154结构域的TNF-α配体多肽的核酸分子公开(公告)号：US20120116052A1
公开(公告)日：2012-05-10
申请号：US13106675
申请日：2011-05-12
CPC分类号： C07K14/525 , A61K38/00 , C07K2319/00
摘要： The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNFα, comprising a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNFα, wherein the encoded domain or subdomain replaces a cleavage site of native TNFα, and a second nucleotide sequence encoding a domain or subdomain of native TNFα that binds to a TNFα receptor. The encoded chimeric TNFα is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNFα receptor on the surface of a cell. The chimeric TNFα is therefore useful in methods for inducing apoptosis of a cell expressing a TNFα receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNFα that is expressed on the surface of the cell.
摘要翻译： 本发明涉及编码嵌合TNFα的分离的多核苷酸序列，其包含编码除TNFα之外的肿瘤坏死因子配体的结构域或亚结构域的第一核苷酸序列，其中编码的结构域或亚结构域替代天然TNFα的切割位点，以及 编码结合TNFα受体的天然TNFα的结构域或亚结构域的第二核苷酸序列。 编码的嵌合TNFα对细胞表面的切割显着较不敏感，结果可以增加能够结合细胞表面的TNFα受体的配体的浓度。 因此，嵌合TNFα可用于诱导表达TNFα受体的细胞的凋亡，诱导免疫系统细胞的活化和治疗肿瘤细胞的方法，通过将编码嵌合TNFα的分离的多核苷酸序列引入感兴趣的细胞中，所述多核苷酸序列表达于 电池的表面。
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9.发明授权Nucleic acid molecules encoding TNF-α ligand polypeptides having a CD154 domain 有权编码具有CD154结构域的TNF-α配体多肽的核酸分子公开(公告)号：US07786282B2
公开(公告)日：2010-08-31
申请号：US10006305
申请日：2001-12-06
CPC分类号： C07K14/525 , A61K38/00 , C07K2319/00
摘要： The present invention is directed to an isolated polynucleotide sequence encoding a chimeric TNFα and chimeric TNFα polypeptides. The former have a first nucleotide sequence encoding a domain or subdomain of a tumor necrosis factor ligand other than TNFα, wherein the encoded domain or subdomain lacks a cleavage site, and a second nucleotide sequence encoding a domain or subdomain of native TNFα that binds to a TNFα receptor. The encoded chimeric TNFα is significantly less susceptible to cleavage from the cellular surface and, as a result can increase the concentration of a ligand capable of binding to a TNFα receptor on the surface of a cell. The chimeric TNFα is therefore useful in methods for inducing apoptosis of a cell expressing a TNFα receptor, inducing activation of an immune system cell and treating neoplastic cells, by introducing into the cell of interest an isolated polynucleotide sequence encoding a chimeric TNFα that is expressed on the surface of the cell.
摘要翻译： 本发明涉及编码嵌合TNFα和嵌合TNFα多肽的分离的多核苷酸序列。 前者具有编码除TNFα之外的肿瘤坏死因子配体的结构域或亚结构域的第一核苷酸序列，其中编码的结构域或亚结构域缺乏切割位点，以及编码天然TNFα结构域或亚结构域的第二核苷酸序列 TNFα受体。 编码的嵌合TNFα对细胞表面的切割显着较不敏感，结果可以增加能够结合细胞表面的TNFα受体的配体的浓度。 因此，嵌合TNFα可用于诱导表达TNFα受体的细胞的凋亡，诱导免疫系统细胞的活化和治疗肿瘤细胞的方法，通过将编码嵌合TNFα的分离的多核苷酸序列引入感兴趣的细胞中，所述多核苷酸序列表达于 电池的表面。
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