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1.发明授权Methods of ex-vivo expansion of hematopoietic cells using interleukin-3 (IL-3) multiple mutation polypeptides 失效使用白细胞介素-3（IL-3）多重突变多肽的造血细胞离体扩增的方法公开(公告)号：US06440407B1
公开(公告)日：2002-08-27
申请号：US08764114
申请日：1996-12-09
申请人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
发明人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
IPC分类号： C12N508
CPC分类号： C07K14/5403 , A61K38/00 , C07K2319/00 , C07K2319/02 , Y10S930/141
摘要： The present invention relates to methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a variant of human interleukin-3 (hIL-3) which contains multiple amino acid substitutions and which may have portions of the native hIL-3 molecule deleted. The present invention also relates to the ex-vivo expansion of hematopoietic cells for gene therapy. Additionally, the present invention relates to the use of the expanded hematopoietic cells for treating patients having a hematopoietic disorder.
摘要翻译： 本发明涉及通过在包含多个氨基酸取代的人白细胞介素-3（hIL-3）的变体的生长培养基中培养造血细胞而造血细胞离体扩增的方法，其可以具有天然hIL的部分 -3分子删除。 本发明还涉及用于基因治疗的造血细胞的离体扩增。 此外，本发明涉及扩大的造血细胞用于治疗造血障碍的患者的用途。
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2.发明授权Methods of ex-vivo expansion of hematopoietic cells using multivariant IL-3 hematopoiesis chimera proteins 失效使用多变量IL-3造血嵌合体蛋白质造血细胞离体扩增的方法公开(公告)号：US06436387B1
公开(公告)日：2002-08-20
申请号：US08762227
申请日：1996-12-09
申请人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
发明人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
IPC分类号： A61K4500
CPC分类号： C07K14/5403 , A61K38/00 , C07K2319/00 , C07K2319/02
摘要： The present invention relates to methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a chimera protein which comprises a variant of human interleukin-3 (hIL-3) which contains multiple amino acid substitutions and which may have portions of the native hIL-3 molecule deleted and a hematopoietic growth factor. The present invention also relates to the ex-vivo expansion of hematopoietic cells for gene therapy. Additionally, the present invention relates to the use of the expanded hematopoietic cells for treating patients having a hematopoietic disorder.
摘要翻译： 本发明涉及通过在包含嵌合体蛋白质的生长培养基中培养造血细胞的造血细胞的离体扩增方法，所述嵌合体蛋白质包含含有多个氨基酸取代的人白细胞介素-3（hIL-3）的变体， 天然hIL-3分子缺失的部分和造血生长因子。 本发明还涉及用于基因治疗的造血细胞的离体扩增。 此外，本发明涉及扩大的造血细胞用于治疗造血障碍的患者的用途。
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3.发明授权Co-administration of interleukin-3 mutant polypeptides with CSF'S for multi-lineage hematopoietic cell production 失效将白细胞介素-3突变体多肽与CSFS共同给予多谱系造血细胞生产公开(公告)号：US06361976B1
公开(公告)日：2002-03-26
申请号：US08446871
申请日：1995-06-06
申请人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
发明人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
IPC分类号： C12N2100
CPC分类号： C07K14/5403 , A61K38/00 , A61K38/18 , A61K38/1816 , A61K38/193 , A61K38/20 , A61K38/27 , C07K2319/00 , C07K2319/02 , A61K2300/00
摘要： The present invention relates to human interleukin-3 (hIL-3) variant or mutant proteins (muteins) functionally co-administered with a other colony stimulating factors (CSF), cytokines, lymphokines, interleukins, hematopoietic growth factors or IL-3 variants.
摘要翻译： 本发明涉及与其它集落刺激因子（CSF），细胞因子，淋巴因子，白细胞介素，造血生长因子或IL-3变体功能性共同施用的人白细胞介素-3（hIL-3）变体或突变蛋白（突变蛋白）。
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4.发明授权Co-administration of interleukin-3 mutant polypeptides with CSF's for multi-lineage hematopoietic cell production 失效共同给予白细胞介素-3突变体多肽与CSF用于多系造血细胞生产
公开(公告)号：US6060047A
公开(公告)日：2000-05-09
申请号：US471045
申请日：1995-06-06
申请人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
发明人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
CPC分类号： A61K45/00 , A61K38/1816 , A61K38/193 , C07K14/5403 , A61K38/00
摘要： The present invention relates to human interleukin-3 (hIL-3) variant or mutant proteins (muteins) functionally co-administered with other colony stimulating factors (CSF), cytokines, lymphokines, interleukins, hematopoietic growth factors or IL-3 variants.
摘要翻译： 本发明涉及与其他集落刺激因子（CSF），细胞因子，淋巴因子，白介素，造血生长因子或IL-3变体功能性共同施用的人白细胞介素-3（hIL-3）变体或突变蛋白（突变蛋白）。
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5.发明授权
公开(公告)号：US6051217A
公开(公告)日：2000-04-18
申请号：US470081
申请日：1995-06-06
申请人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
发明人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
IPC分类号： C12N15/09 , A61K38/00 , A61K38/20 , A61K45/00 , A61P7/00 , A61P43/00 , C07H21/04 , C07K1/00 , C07K14/00 , C07K14/54 , C07K17/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/08 , C12N5/10 , C12N15/24 , C12N15/61 , C12P21/02 , C12P21/04 , C12R1/19
CPC分类号： C07K14/5403 , A61K38/00 , C07K2319/00 , C07K2319/02 , Y10S930/141
摘要： The present invention relates to recombinant human interleukin-3 (hIL-3) variant or mutant proteins (muteins). These hIL-3 muteins contain amino acid substitutions and may also have amino acid deletions at both the N- and C-termini. The invention also relates to pharmaceutical compositions containing the hIL-3 muteins and methods for using them. Additionally, the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the hIL-3 muteins, related microbial expression systems, and processes for making the hIL-3 muteins using the microbial expression systems. Included in the present invention are deletion mutants of hIL-3 in which from 1 to 14 amino acids have been deleted from the N-terminus, and from 1 to 15 amino acids (a.a.119 to 133) have been deleted from the C-terminus, and which also contain amino acid substitutions in the polypeptide. These hIL-3 multiple mutation polypeptides may have biological activities similar to or better than hIL-3 and, in some cases, may also have an improved side effect profile.
摘要翻译： 本发明涉及重组人白细胞介素-3（hIL-3）变体或突变蛋白（突变蛋白）。 这些hIL-3突变蛋白含有氨基酸取代，并且在N-和C-末端也可具有氨基酸缺失。 本发明还涉及含有hIL-3突变蛋白的药物组合物及其使用方法。 另外，本发明涉及包含编码hIL-3突变蛋白的核苷酸序列，相关微生物表达系统和使用微生物表达系统制备hIL-3突变蛋白的方法的重组表达载体。 本发明包括hIL-3的缺失突变体，其中从N末端缺失1至14个氨基酸，从C末端缺失1至15个氨基酸（aa119至133） ，并且其还在多肽中含有氨基酸取代。 这些hIL-3多重突变多肽可具有类似于或优于hIL-3的生物学活性，并且在一些情况下也可具有改善的副作用特征。
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公开(公告)号：US06361977B1
公开(公告)日：2002-03-26
申请号：US08446872
申请日：1995-06-06
申请人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
发明人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
IPC分类号： C12P2104
CPC分类号： C07K14/5403 , A61K38/00 , C07K2319/00 , C07K2319/02
摘要： The present invention relates to human interleukin-3 (hIL-3) variant or mutant proteins (muteins) fused with other colony stimulating factors (CSF), cytokines, lymphokines, interleukins, hematopoietic growth factors or IL-3 variants.
摘要翻译： 本发明涉及与其他集落刺激因子（CSF），细胞因子，淋巴因子，白介素，造血生长因子或IL-3变体融合的人白细胞介素-3（hIL-3）变体或突变蛋白（突变蛋白）。
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7.发明授权Co-administration of interleukin-3 mutant polypeptides with CSF's for multi-lineage hematopoietic cell production 失效共同给予白细胞介素-3突变体多肽与CSF用于多系造血细胞生产
公开(公告)号：US06093395A
公开(公告)日：2000-07-25
申请号：US469712
申请日：1995-06-06
申请人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
发明人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
CPC分类号： A61K45/00 , A61K38/1816 , A61K38/193 , C07K14/5403 , A61K38/00
摘要： The present invention relates to human interleukin-3 (hIL-3) variant or mutant proteins (muteins) functionally co-administered with other colony stimulating factors (CSF's), cytokines, lymphokines, interleukins, hematopoietic growth factors or IL-3 variants.
摘要翻译： 本发明涉及与其他集落刺激因子（CSF），细胞因子，淋巴因子，白细胞介素，造血生长因子或IL-3变体功能性共同施用的人白细胞介素-3（hIL-3）变体或突变蛋白（突变蛋白）。
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8.发明授权Methods of ex-vivo expansion of hematopoietic cells using interleukin-3 mutant polypeptides with other hematopoietic growth factors 失效使用白介素-3突变体多肽与其他造血生长因子的造血细胞离体扩增的方法公开(公告)号：US06413509B1
公开(公告)日：2002-07-02
申请号：US08761907
申请日：1996-12-09
申请人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John Thomas
发明人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John Thomas
IPC分类号： A61K4500
CPC分类号： C07K14/5403 , A61K35/28 , C07K2319/00 , C07K2319/02 , C12N5/0647 , C12N15/00
摘要： The present invention relates to methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a variant of human interleukin-3 (hIL-3), which contains multiple amino acid substitutions and which may have portions of the native hIL-3 molecule deleted, and a hematopoietic growth factor. The present invention also relates to the ex-vivo expansion of hematopoietic cells for gene therapy. Additionally, the present invention relates to the use of the expanded hematopoietic cells for treating patients having a hematopoietic disorder.
摘要翻译： 本发明涉及通过在包含多个氨基酸取代的人白细胞介素-3（hIL-3）的变体的生长培养基中培养造血细胞而造血细胞的离体扩增的方法，其可以具有天然部分 hIL-3分子缺失，和造血生长因子。 本发明还涉及用于基因治疗的造血细胞的离体扩增。 此外，本发明涉及扩大的造血细胞用于治疗造血障碍的患者的用途。
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9.发明授权Interleukin-3 (IL-3) variant fusion proteins, their recombinant production, and therapeutic compositions comprising them 失效白细胞介素-3（IL-3）变体融合蛋白，其重组生产和包含它们的治疗组合物
公开(公告)号：US5738849A
公开(公告)日：1998-04-14
申请号：US192299
申请日：1994-02-04
申请人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John Warren Thomas
发明人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan Michael Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John Warren Thomas
IPC分类号： C12N15/09 , A61K38/00 , A61K38/22 , A61K38/27 , A61P7/06 , C07K14/53 , C07K14/535 , C07K14/54 , C07K19/00 , C12N15/24 , C12P21/02 , A61K38/19 , A61K38/20 , C12N15/62
CPC分类号： C07K14/535 , C07K14/5403 , A61K38/00 , C07K2319/00 , C07K2319/02 , Y10S930/141
摘要： The present invention relates to fusion molecules composed of human interleukin-3 (hIL-3) variant or mutant proteins (muteins) functionally joined to a second colony stimulating factor (CSF), cytokine, lymphokine, interleukin or IL-3 variant. These hIL-3 variants contain amino acid substitutions and may also have amino acid deletions at both the N- and C- termini. The invention also relates to pharmaceutical compositions containing the fusion molecules and methods for using them.
摘要翻译： 本发明涉及由功能性地连接到第二集落刺激因子（CSF），细胞因子，淋巴因子，白细胞介素或IL-3变体的人白细胞介素-3（hIL-3）变体或突变蛋白（突变蛋白）组成的融合分子。 这些hIL-3变体含有氨基酸取代，并且在N-和C-末端也可具有氨基酸缺失。 本发明还涉及含有该融合分子的药物组合物及其使用方法。
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10.发明授权Fusion proteins comprising multiply mutated interleukin-3 (IL-3) polypeptides and second growth factors 失效包含多重突变白细胞介素-3（IL-3）多肽和第二生长因子的融合蛋白
公开(公告)号：US6030812A
公开(公告)日：2000-02-29
申请号：US468609
申请日：1995-06-06
申请人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan M. Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
发明人： S. Christopher Bauer , Mark Allen Abrams , Sarah Ruth Braford-Goldberg , Maire Helena Caparon , Alan M. Easton , Barbara Kure Klein , John P. McKearn , Peter O. Olins , Kumnan Paik , John W. Thomas
IPC分类号： C12N15/09 , A47B47/02 , A61K38/00 , A61K38/20 , A61K38/22 , A61K38/27 , A61P7/00 , C07H21/04 , C07K20060101 , C07K14/52 , C07K14/53 , C07K14/54 , C07K19/00 , C12N1/21 , C12N15/24 , C12N15/26 , C12N15/27 , C12N15/62 , C12N15/63 , C12P21/02 , C12R1/19
CPC分类号： C07K14/5403 , A61K38/00 , C07K2319/00 , C07K2319/02
摘要： The present invention relates to human interleukin-3 (hIL-3) variant or mutant proteins (muteins) fused with other colony stimulating factors (CSF), cytokines, lymphokines, interleukins, hematopoietic growth factors or IL-3 variants.
摘要翻译： 本发明涉及与其他集落刺激因子（CSF），细胞因子，淋巴因子，白介素，造血生长因子或IL-3变体融合的人白细胞介素-3（hIL-3）变体或突变蛋白（突变蛋白）。
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