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11. 发明授权

US5543141A Therapeutic methods using interleukin-3 (IL-3) human/murine hybrid polypeptides 失效
标题翻译：使用白细胞介素-3（IL-3）人/鼠杂交多肽的治疗方法
公开(公告)号：US5543141A
公开(公告)日：1996-08-06
申请号：US466647
申请日：1995-06-06
申请人： Sarah R. Braford-Goldberg , Alan M. Easton , Barbara K. Klein , John P. McKearn , Peter O. Olins
发明人： Sarah R. Braford-Goldberg , Alan M. Easton , Barbara K. Klein , John P. McKearn , Peter O. Olins
IPC分类号： A61K38/00 , C07K14/54 , C12N15/24 , A61K38/20
CPC分类号： C07K14/5403 , A61K38/00
摘要： The present invention relates to recombinant human interleukin-3 (hIL-3) variant or mutant proteins (muteins) in which segments of the polypeptide sequence of the human IL-3 polypeptide have been replaced by segments of the murine (mouse) interleukin-3 (mIL-3) polypeptide to form human/murine chimeric hybrid polypeptides. The human/mouse IL-3 may have amino acid deletions at the N-terminus or the C-terminus or at both the N- and C- termini and in some cases may also contain additional amino acid substitutions or deletions. The human/murine IL-3 muteins retain at least one biological activity of native hIL-3 and may also exhibit an improved side effects profile such as a reduction in the stimulation of leukotriene release or histamine release. The invention also relates to pharmaceutical compositions containing the h/m IL-3 hybrids and methods for using them. Additionally, the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the IL-3 hybrid muteins, related microbial expression systems, and processes for making the IL-3 hybrids using the microbial expression systems.
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），其中人IL-3多肽的多肽序列的片段已被鼠（小鼠）白介素-3 （mIL-3）多肽以形成人/鼠嵌合杂合多肽。人/小鼠IL-3可以在N末端或C末端或在N-和C-末端具有氨基酸缺失，并且在一些情况下也可能含有额外的氨基酸取代或缺失。人/鼠IL-3突变蛋白保留天然hIL-3的至少一种生物活性，并且还可以表现出改善的副作用特征，例如减少刺激白三烯释放或组胺释放。本发明还涉及含有h / m IL-3杂交体的药物组合物及其使用方法。此外，本发明涉及包含编码IL-3杂交突变蛋白的核苷酸序列，相关的微生物表达系统和使用微生物表达系统制备IL-3杂交体的方法的重组表达载体。

12. 发明授权

US5501962A Interleuken-3 (IL-3) human/murine hybrid polypeptides and recombinant production of the same 失效
标题翻译：白细胞介素-3（IL-3）人/鼠杂交多肽及其重组生产
公开(公告)号：US5501962A
公开(公告)日：1996-03-26
申请号：US081539
申请日：1993-06-21
申请人： Sarah R. Braford-Goldberg , Alan M. Easton , Barbara K. Klein , John P. McKearn , Peter O. Olins
发明人： Sarah R. Braford-Goldberg , Alan M. Easton , Barbara K. Klein , John P. McKearn , Peter O. Olins
IPC分类号： A61K38/00 , C07K14/54 , C12N15/24 , A61K38/20 , C12N15/27
CPC分类号： C07K14/5403 , A61K38/00
摘要： The present invention relates to recombinant human interleukin-3 (hIL-3) variant or mutant proteins (muteins) in which segments of the polypeptide sequence of the human IL-3 polypeptide have been replaced by segments of the murine (mouse) interleukin-3 (mIL-3) polypeptide to form human/murine chimeric hybrid polypeptides. The human/mouse hybrid IL-3 may have amino acid deletions at the N-terminus or the C-terminus or at both the N- and C- termini and in some cases may also contain additional amino acid substitutions or deletions. The human/murine IL-3 muteins retain at least one biological activity of native hIL-3 and may also exhibit an improved side effects profile such as a reduction in the stimulation of leukotriene release or histamine release. The invention also relates to pharmaceutical compositions containing the h/m IL-3 hybrids and methods for using them. Additionally, the present invention relates to recombinant expression vectors comprising nucleotide sequences encoding the IL-3 hybrid muteins, related microbial expression systems, and processes for making the IL-3 hybrids using the microbial expression systems.
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），其中人IL-3多肽的多肽序列的片段已被鼠（小鼠）白介素-3 （mIL-3）多肽以形成人/鼠嵌合杂合多肽。人/小鼠混合IL-3可以在N-末端或C-末端或在N-和C-末端具有氨基酸缺失，并且在一些情况下也可能含有额外的氨基酸取代或缺失。人/鼠IL-3突变蛋白保留天然hIL-3的至少一种生物活性，并且还可以表现出改善的副作用特征，例如减少刺激白三烯释放或组胺释放。本发明还涉及含有h / m IL-3杂交体的药物组合物及其使用方法。此外，本发明涉及包含编码IL-3杂交突变蛋白的核苷酸序列，相关的微生物表达系统和使用微生物表达系统制备IL-3杂交体的方法的重组表达载体。

13. 发明授权

US06833373B1 Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia 失效
标题翻译：使用整联蛋白拮抗剂和一种或多种抗肿瘤剂作为组合疗法治疗瘤形成的方法
公开(公告)号：US06833373B1
公开(公告)日：2004-12-21
申请号：US09857994
申请日：2001-10-05
申请人： John P. McKearn , Gary Gordon , James J. Cunningham , Stephen T. Gately , Alane T. Koki , Jaime L. Masferrer
发明人： John P. McKearn , Gary Gordon , James J. Cunningham , Stephen T. Gately , Alane T. Koki , Jaime L. Masferrer
IPC分类号： A61K31505
CPC分类号： A61K33/24 , A61K31/135 , A61K31/415 , A61K31/42 , A61K31/445 , A61K31/505 , A61K31/506 , A61K31/675 , A61K41/00 , A61K41/0038 , A61K45/06 , A61K2300/00
摘要： The present invention provides methods to treat or prevent neoplasia disorders in a mammal using a combination of an integrin antagonist and an antineoplastic agent.
摘要翻译：本发明提供了使用整联蛋白拮抗剂和抗肿瘤剂的组合来治疗或预防哺乳动物中的肿瘤形成障碍的方法。

14. 发明授权

US06413509B1 Methods of ex-vivo expansion of hematopoietic cells using interleukin-3 mutant polypeptides with other hematopoietic growth factors 失效
标题翻译：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。

15. 发明授权

US06379662B1 Co-administration of interleukin-3 mutant polypeptides with CSF's for multi-lineage hematopoietic cell production 失效
标题翻译：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：US06379662B1
公开(公告)日：2002-04-30
申请号：US08468910
申请日：1995-06-06
申请人： John P. McKearn , Peter Olins , John Thomas , Maire Caparon , Alan Easton , Barbara Klein , S. Christopher Bauer , Mark Abrams , Kumnan Paik , Sarah Braford-Goldberg
发明人： John P. McKearn , Peter Olins , John Thomas , Maire Caparon , Alan Easton , Barbara Klein , S. Christopher Bauer , Mark Abrams , Kumnan Paik , Sarah Braford-Goldberg
IPC分类号： A61K4500
CPC分类号： A61K45/00 , A61K38/00 , A61K38/1816 , A61K38/193 , C07K14/5403 , 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）。

16. 发明授权

US6100070A G-CSF receptor agonists 失效
公开(公告)号：US6100070A
公开(公告)日：2000-08-08
申请号：US833167
申请日：1997-04-04
申请人： Linda L. Zurfluh , Barbara K. Klein , Charles A. McWherrter , Yiqing Feng , John P. McKearn , Sarah Ruth Braford-Goldberg
发明人： Linda L. Zurfluh , Barbara K. Klein , Charles A. McWherrter , Yiqing Feng , John P. McKearn , Sarah Ruth Braford-Goldberg
IPC分类号： A61C7/06 , C07K14/53 , C12N15/27 , C07K14/535 , C12N15/63
CPC分类号： C07K14/535 , A61C7/06 , C07K14/53 , A61K38/00
摘要： Disclosed are novel G-CSF receptor agonist proteins, DNAs which encode the multi-functional hematopoietic receptor agonists proteins, methods of making the multi-functional hematopoietic receptor agonists proteins and methods of using the multi-functional hematopoietic receptor agonists proteins.

17. 发明授权

US6066318A Multi-functional hematopoietic fusion proteins between sequence rearranged C-MPL receptor agonists and other hematopoietic factors 失效
标题翻译：序列重排C-MPL受体激动剂与其他造血因子之间的多功能造血融合蛋白
公开(公告)号：US6066318A
公开(公告)日：2000-05-23
申请号：US835162
申请日：1997-04-04
申请人： Yiqing Feng , Nicholas R. Staten , Charles M. Baum , Neena L. Summers , Maire Helena Caparon , S. Christopher Bauer , Linda L. Zurfluh , John P. McKearn , Barbara K. Klein , Stephen C. Lee , Charles A. McWherter , Judith G. Giri
发明人： Yiqing Feng , Nicholas R. Staten , Charles M. Baum , Neena L. Summers , Maire Helena Caparon , S. Christopher Bauer , Linda L. Zurfluh , John P. McKearn , Barbara K. Klein , Stephen C. Lee , Charles A. McWherter , Judith G. Giri
IPC分类号： A61K35/12 , A61K38/00 , A61K39/00 , A61K48/00 , C07K14/52 , C07K14/53 , C07K14/54 , C12N15/12 , C12N15/62
CPC分类号： C07K14/5403 , C07K14/524 , C07K14/53 , C12N15/62 , A61K2035/124 , A61K2039/51 , A61K38/00 , A61K48/00 , C07K2319/00 , C07K2319/75
摘要： Disclosed are novel multi-functional hematopoietic receptor agonist proteins, DNAs which encode the multi-functional hematopoietic receptor agonists proteins, methods of making the multi-functional hematopoietic receptor agonists proteins and methods of using the multi-functional hematopoietic receptor agonists proteins.
摘要翻译：公开了新型多功能造血受体激动剂蛋白质，编码多功能造血受体激动剂蛋白质的DNA，制备多功能造血受体激动剂蛋白质的方法和使用多功能造血受体激动剂蛋白质的方法。

18. 发明授权

US6051217A Therapeutic uses of interleukin-3 (IL-3) multiple mutation polypeptides 失效
标题翻译：白细胞介素-3（IL-3）多重突变多肽的治疗用途
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。

19. 发明授权

US5738849A Interleukin-3 (IL-3) variant fusion proteins, their recombinant production, and therapeutic compositions comprising them 失效
标题翻译：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。

20. 发明授权

US5486539A Method of using phenylacetonitrilealkylaminoalkyl-ortho-substituted aryl compounds as immunosuppressives 失效
标题翻译：使用苯乙腈烷基氨基烷基邻位取代的芳基化合物作为免疫抑制剂的方法
公开(公告)号：US5486539A
公开(公告)日：1996-01-23
申请号：US204121
申请日：1994-03-01
申请人： Chi-Dean Liang , John P. McKearn , John M. Farah, Jr. , Richard A. Mueller
发明人： Chi-Dean Liang , John P. McKearn , John M. Farah, Jr. , Richard A. Mueller
IPC分类号： C07C255/43 , A61K31/275
CPC分类号： C07C255/43
摘要： A class of substituted phenylacetonitrile-alkylaminoalkyl-ortho-substituted aryl compounds having immunosuppressive properties is described. Compounds of this class would be useful in reducing recipient rejection of transplanted organs and for treatment of autoimmune or inflammatory diseases. Compounds of particular interest are of the formula ##STR1## wherein m is one or two; wherein n is a number selected from one to five, inclusive; wherein R.sup.1 is selected from hydrido, alkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, alkenyl and alkynyl; wherein R.sup.6 is selected from loweralkyl; wherein each of R.sup.8, R.sup.9, R.sup.10 and R.sup.12 through R.sup.16 is independently selected from hydrido, hydroxy, alkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylalkenyl, alkylaminocarbonyl and alkoxyalkyl; with the proviso that at least one of R.sup.12 and R.sup.16 must be selected from hydroxy, alkyl, hydroxyalkyl, alkoxy, alkenyl, alkynyl, alkylcarbonyl, alkoxycarbonyl, alkylcarbonylalkenyl, alkylaminocarbonyl and alkoxyalkyl; or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
摘要翻译：描述了一类具有免疫抑制特性的取代的苯基乙腈 - 烷基氨基烷基邻位取代的芳基化合物。该类化合物可用于减少移植器官的受体排斥和治疗自身免疫性或炎性疾病。特别感兴趣的化合物具有下式：其中m是一个或两个; 其中n是选自1至5的数字，包括1和5; 其中R1选自氢化，烷基，羟基烷基，环烷基，环烷基烷基，烷氧基烷基，烯基和炔基; 其中R 6选自低级烷基; 其中R8，R9，R10和R12至R16各自独立地选自氢，羟基，烷基，羟基烷基，烷氧基，烯基，炔基，烷基羰基，烷氧基羰基，烷基羰基烯基，烷基氨基羰基和烷氧基烷基; 条件是R12和R16中的至少一个必须选自羟基，烷基，羟烷基，烷氧基，烯基，炔基，烷基羰基，烷氧基羰基，烷基羰基烯基，烷基氨基羰基和烷氧基烷基; 或其互变异构体或其药学上可接受的盐。

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