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1. 发明申请

WO2008014054A3 BMP-7 VARIANT COMPOSITIONS, METHODS AND USES 审中-公开
标题翻译： BMP-7变体组合物，方法和用途
公开(公告)号：WO2008014054A3
公开(公告)日：2009-04-09
申请号：PCT/US2007070584
申请日：2007-06-07
申请人： CENTOCOR INC , AMEGADZIE BERNARD , CUNNINGHAM MARK R , DORAI HAIMANTI , LUO JEFFREY , MILLS JULIANE , SWENCKI-UNDERWOOD BETHANY
发明人： AMEGADZIE BERNARD , CUNNINGHAM MARK R , DORAI HAIMANTI , LUO JEFFREY , MILLS JULIANE , SWENCKI-UNDERWOOD BETHANY
IPC分类号： C12N15/00 , A61K38/16 , A61K38/18 , C07K14/00 , C07K14/435 , C07K14/46 , C07K14/475 , C07K14/51 , C12N15/12 , C12N15/63
CPC分类号： C07K14/51 , A61K38/00
摘要： Human Bone Morphogenic Protein 7 (hBMP-7) variant peptide chains, nucleic acids encoding these peptide chains, and methods of making and using the foregoing are disclosed.
摘要翻译：公开了人骨形态发生蛋白7（hBMP-7）变体肽链，编码这些肽链的核酸，以及制备和使用前述物质的方法。

2. 发明申请

WO2007087053A2 BMP-7 VARIANT COMPOSITIONS, METHODS AND USES 审中-公开
标题翻译： BMP-7变体组合物，方法和用途
公开(公告)号：WO2007087053A2
公开(公告)日：2007-08-02
申请号：PCT/US2006/048730
申请日：2006-12-20
申请人： CENTOCOR, INC , AMEGADZIE, Bernard , CUNNINGHAM, Mark R. , LUO, Jeffrey , MILLS, Juliane , SWENCKI-UNDERWOOD, Bethany
发明人： AMEGADZIE, Bernard , CUNNINGHAM, Mark R. , LUO, Jeffrey , MILLS, Juliane , SWENCKI-UNDERWOOD, Bethany
IPC分类号： A61K38/18
CPC分类号： C07K14/51 , A61K38/00
摘要： Human Bone Morphogenic Protein 7 (hBMP-7) variant peptide chains, nucleic acids encoding these peptide chains, and methods of making and using the foregoing are disclosed.
摘要翻译：公开了人骨形态发生蛋白7（hBMP-7）变体肽链，编码这些肽链的核酸，以及制备和使用前述物质的方法。

3. 发明申请

WO2008079976A3 DIMERIC HIGH AFFINITY EGFR CONSTRUCTS AND USES THEREOF 审中-公开
标题翻译：二聚体高亲和力EGFR构建体及其用途
公开(公告)号：WO2008079976A3
公开(公告)日：2008-11-27
申请号：PCT/US2007088376
申请日：2007-12-20
申请人： CENTOCOR INC , WANG BRYAN , SHI FRANK , MILLS JULIANE
发明人： WANG BRYAN , SHI FRANK , MILLS JULIANE
IPC分类号： C07K1/00 , A61K38/00 , C12Q1/00
CPC分类号： C07K14/71 , A61K38/00 , C07K2319/30
摘要： Polypeptides comprising EGFR extracellular domains I-III capable of forming dimeric EGF-binding proteins are provided. The dimeric construct of the invention is useful in applications where high affinity EGF binding is desired and can be used to select agents capable of binding to native EGFR in the presence of EGF.
摘要翻译：提供了包含能够形成二聚体EGF结合蛋白的EGFR胞外结构域I-III的多肽。本发明的二聚体构建体可用于需要高亲和力EGF结合的应用，并且可用于在EGF存在下选择能够结合天然EGFR的试剂。

4. 发明申请

WO2008079976A2 DIMERIC HIGH AFFINITY EGFR CONSTRUCTS AND USES THEREOF 审中-公开
标题翻译：二重高度的EGFR结构及其用途
公开(公告)号：WO2008079976A2
公开(公告)日：2008-07-03
申请号：PCT/US2007/088376
申请日：2007-12-20
申请人： CENTOCOR, INC. , WANG, Bryan , SHI, Frank , MILLS, Juliane
发明人： WANG, Bryan , SHI, Frank , MILLS, Juliane
IPC分类号： A61K38/18
CPC分类号： C07K14/71 , A61K38/00 , C07K2319/30
摘要： Polypeptides comprising EGFR extracellular domains I-III capable of forming dimeric EGF-binding proteins are provided. The dimeric construct of the invention is useful in applications where high affinity EGF binding is desired and can be used to select agents capable of binding to native EGFR in the presence of EGF.
摘要翻译：提供了包含能够形成二聚体EGF结合蛋白的EGFR细胞外结构域I-III的多肽。本发明的二聚体构建体可用于需要高亲和力EGF结合并且可用于选择能够在EGF存在下与天然EGFR结合的试剂的应用中。

5. 发明申请

WO2008014054A2 BMP-7 VARIANT COMPOSITIONS, METHODS AND USES 审中-公开
标题翻译： BMP-7变体组合物，方法和用途
公开(公告)号：WO2008014054A2
公开(公告)日：2008-01-31
申请号：PCT/US2007/070584
申请日：2007-06-07
申请人： CENTOCOR, INC. , AMEGADZIE, Bernard , CUNNINGHAM, Mark , DORAI, Haimanti , LUO, Jeffrey , MILLS, Juliane , SWENCKI-UNDERWOOD, Bethany
发明人： AMEGADZIE, Bernard , CUNNINGHAM, Mark , DORAI, Haimanti , LUO, Jeffrey , MILLS, Juliane , SWENCKI-UNDERWOOD, Bethany
IPC分类号： A61K38/02 , A61P19/00 , C07H21/00 , C07K2/00 , C12N1/00 , C12N15/63 , C12P21/00
CPC分类号： C07K14/51 , A61K38/00
摘要： Human Bone Morphogenic Protein 7 (hBMP-7) variant peptide chains, nucleic acids encoding these peptide chains, and methods of making and using the foregoing are disclosed.
摘要翻译：公开了人骨形态发生蛋白7（hBMP-7）变体肽链，编码这些肽链的核酸，以及制备和使用前述物质的方法。

6. 发明申请

WO2005065239A8 NOVEL RECOMBINANT PROTEINS WITH N-TERMINAL FREE THIOL 审中-公开
标题翻译：新型重组蛋白与N-末端免费THIOL
公开(公告)号：WO2005065239A8
公开(公告)日：2006-08-17
申请号：PCT/US2004043081
申请日：2004-12-23
申请人： CENTOCOR INC , POOL CHADLER , MILLS JULIANE , CUNNINGHAM MARK
发明人： POOL CHADLER , MILLS JULIANE , CUNNINGHAM MARK
IPC分类号： C12N9/96 , C07H21/04 , C07K1/00 , C07K1/107 , C07K14/505 , C12N15/85 , C12P21/02
CPC分类号： C07K1/1075 , C07K1/1077 , C07K14/505
摘要： The present invention relates to novel modified proteins having N-terminal free thiols that can be produced by recombinant methods and are ready for further chemical derivatization. In particular, the invention relates to erythropoietin conjugate compounds having altered biochemical, physiochemical and pharmacokinetic properties. More particularly, one embodiment of the invention relates to erythropoietin conjugate compounds of the formula: (M)n-X-A-cys-EPO (I) where EPO is an erythropoeitin moiety selected from erythropoietin or an erythropoietin variant having at least one amino acid different from the wild-type human EPO, or any pharmaceutical acceptable derivatives thereof having biological properties of causing bone marrow cells to increase production of red blood cells; cys represents the amino acid cysteine and occurs at position -1 relative to the amino acid sequence of the erythropoietin moiety; A indicates the structure of the residual moiety used to chemically attach X to the thiol group of -1Cys; X is a water soluble polymer such as a polyalkylene glycol or other polymer; M is an organic molecule (including peptides and proteins) that increases the circulating half-life of the construct; and N is an integer from 0 to 15.
摘要翻译：本发明涉及具有N-末端游离硫醇的新型修饰蛋白，其可通过重组方法制备并准备进一步化学衍生化。特别地，本发明涉及具有改变的生物化学，生理化学和药代动力学性质的红细胞生成素缀合物化合物。更具体地，本发明的一个实施方案涉及下式的促红细胞生成素缀合物化合物：（M）nXA-cys-EPO（I）其中EPO是选自促红细胞生成素或促红细胞生成素变体的红细胞生成素，其具有至少一个不同于野生型人EPO或其具有引起骨髓细胞增加红细胞产生的生物学特性的任何药物可接受的衍生物; cys代表氨基酸半胱氨酸并且发生在相对于促红细胞生成素部分的氨基酸序列的位置-1; A表示用于将X化学连接到-1Cys的硫醇基上的残留部分的结构; X是水溶性聚合物，例如聚亚烷基二醇或其它聚合物; M是增加构建体的循环半衰期的有机分子（包括肽和蛋白质） N为0〜15的整数。

7. 发明申请

WO2005065239A2 NOVEL RECOMBINANT PROTEINS WITH N-TERMINAL FREE THIOL 审中-公开
标题翻译：新型重组蛋白与N-末端免费THIOL
公开(公告)号：WO2005065239A2
公开(公告)日：2005-07-21
申请号：PCT/US2004/043081
申请日：2004-12-23
申请人： CENTOCOR, INC. , POOL, Chadler , MILLS, Juliane , CUNNINGHAM, Mark
发明人： POOL, Chadler , MILLS, Juliane , CUNNINGHAM, Mark
IPC分类号： C07H21/04 , C07K1/00 , C07K1/107 , C07K14/505 , C12N9/96 , C12N15/85 , C12P21/02
CPC分类号： C07K1/1075 , C07K1/1077 , C07K14/505
摘要： The present invention relates to novel modified proteins having N-terminal free thiols that can be produced by recombinant methods and are ready for further chemical derivatization. In particular, the invention relates to erythropoietin conjugate compounds having altered biochemical, physiochemical and pharmacokinetic properties. More particularly, one embodiment of the invention relates to erythropoietin conjugate compounds of the formula: (M)n-X-A-cys-EPO (I) where EPO is an erythropoeitin moiety selected from erythropoietin or an erythropoietin variant having at least one amino acid different from the wild-type human EPO, or any pharmaceutical acceptable derivatives thereof having biological properties of causing bone marrow cells to increase production of red blood cells; cys represents the amino acid cysteine and occurs at position -1 relative to the amino acid sequence of the erythropoietin moiety; A indicates the structure of the residual moiety used to chemically attach X to the thiol group of -1Cys; X is a water soluble polymer such as a polyalkylene glycol or other polymer; M is an organic molecule (including peptides and proteins) that increases the circulating half-life of the construct; and N is an integer from 0 to 15.
摘要翻译：本发明涉及具有N-末端游离硫醇的新型修饰蛋白，其可通过重组方法制备并准备进一步化学衍生化。特别地，本发明涉及具有改变的生物化学，生理化学和药代动力学性质的红细胞生成素缀合物化合物。更具体地，本发明的一个实施方案涉及下式的促红细胞生成素缀合物化合物：（M）nXA-cys-EPO（I）其中EPO是选自促红细胞生成素或促红细胞生成素变体的红细胞生成素，其具有至少一个不同于野生型人EPO或其具有引起骨髓细胞增加红细胞产生的生物学特性的任何药物可接受的衍生物; cys代表氨基酸半胱氨酸并且发生在相对于促红细胞生成素部分的氨基酸序列的位置-1; A表示用于将X化学连接到-1Cys的硫醇基上的残留部分的结构; X是水溶性聚合物，例如聚亚烷基二醇或其它聚合物; M是增加构建体的循环半衰期的有机分子（包括肽和蛋白质） N为0〜15的整数。

8. 发明申请

WO2007087053A3 BMP-7 VARIANT COMPOSITIONS, METHODS AND USES 审中-公开
标题翻译： BMP-7变体组合物，方法和用途
公开(公告)号：WO2007087053A3
公开(公告)日：2008-10-16
申请号：PCT/US2006048730
申请日：2006-12-20
申请人： CENTOCOR INC , AMEGADZIE BERNARD , CUNNINGHAM MARK R , LUO JEFFREY , MILLS JULIANE , SWENCKI-UNDERWOOD BETHANY
发明人： AMEGADZIE BERNARD , CUNNINGHAM MARK R , LUO JEFFREY , MILLS JULIANE , SWENCKI-UNDERWOOD BETHANY
IPC分类号： A61K38/00 , C12P21/04
CPC分类号： C07K14/51 , A61K38/00
摘要： Human Bone Morphogenic Protein 7 (hBMP-7) variant peptide chains, nucleic acids encoding these peptide chains, and methods of making and using the foregoing are disclosed.
摘要翻译：公开了人骨形态发生蛋白7（hBMP-7）变体肽链，编码这些肽链的核酸，以及制备和使用前述的方法。

9. 发明申请

WO2005065239A3 NOVEL RECOMBINANT PROTEINS WITH N-TERMINAL FREE THIOL 审中-公开
标题翻译：具有N-末端游离硫醇的新型重组蛋白
公开(公告)号：WO2005065239A3
公开(公告)日：2005-11-24
申请号：PCT/US2004043081
申请日：2004-12-23
申请人： CENTOCOR INC , POOL CHADLER , MILLS JULIANE , CUNNINGHAM MARK
发明人： POOL CHADLER , MILLS JULIANE , CUNNINGHAM MARK
IPC分类号： C07H21/04 , C07K1/00 , C07K1/107 , C07K14/505 , C12N9/96 , C12N15/85 , C12P21/02
CPC分类号： C07K1/1075 , C07K1/1077 , C07K14/505
摘要： The present invention relates to novel modified proteins having N-terminal free thiols that can be produced by recombinant methods and are ready for further chemical derivatization. In particular, the invention relates to erythropoietin conjugate compounds having altered biochemical, physiochemical and pharmacokinetic properties. More particularly, one embodiment of the invention relates to erythropoietin conjugate compounds of the formula: (M)n-X-A-cys-EPO (I) where EPO is an erythropoeitin moiety selected from erythropoietin or an erythropoietin variant having at least one amino acid different from the wild-type human EPO, or any pharmaceutical acceptable derivatives thereof having biological properties of causing bone marrow cells to increase production of red blood cells; cys represents the amino acid cysteine and occurs at position -1 relative to the amino acid sequence of the erythropoietin moiety; A indicates the structure of the residual moiety used to chemically attach X to the thiol group of -1Cys; X is a water soluble polymer such as a polyalkylene glycol or other polymer; M is an organic molecule (including peptides and proteins) that increases the circulating half-life of the construct; and N is an integer from 0 to 15.
摘要翻译：本发明涉及具有N-末端游离硫醇的新型修饰蛋白，其可以通过重组方法产生并准备用于进一步的化学衍生。特别地，本发明涉及具有改变的生物化学，生理化学和药代动力学性质的促红细胞生成素缀合物化合物。更具体地说，本发明的一个实施方案涉及下式的促红细胞生成素缀合物化合物：（M）nXA-cys-EPO（I）其中EPO是选自红细胞生成素或促红细胞生成素变体的促红细胞生成素部分，所述促红细胞生成素变体具有至少一个不同于野生型人EPO或具有引起骨髓细胞增加红细胞产生的生物学特性的任何药学上可接受的衍生物; cys代表氨基酸半胱氨酸，并且发生在相对于促红细胞生成素部分的氨基酸序列的-1位; A表示用于化学连接X至-1Cys的巯基的残余部分的结构; X是水溶性聚合物，例如聚亚烷基二醇或其他聚合物; M是增加构建体循环半衰期的有机分子（包括肽和蛋白质）; 并且N是0至15的整数。

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