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1. 发明授权

US08080515B2 Method for prevention of platelet aggregation employing and RGD-enriched gelatine-like protein 有权
标题翻译：防止使用富含RGD的明胶样蛋白的血小板聚集的方法
公开(公告)号：US08080515B2
公开(公告)日：2011-12-20
申请号：US12494450
申请日：2009-06-30
申请人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
发明人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
IPC分类号： C07K14/00
CPC分类号： A61K9/5078 , A61K9/1658 , A61K47/42 , C07K14/78 , C12N5/0075 , C12N2533/30 , C12N2533/54
摘要： The invention concerns a cell support comprising an RGD-enriched gelatine that has a more even distribution of RGD sequences than occurring in a natural gelatine and with a minimum level of RGD sequences. More precise the percentage of RGD sequences related to the total number of amino acids is at least 0.4 and if the RGD-enriched gelatine comprises 350 amino acids or more, each stretch of 350 amino acids contains at least one RGD motif. Preferably the RGD-enriched gelatines are prepared by recombinant technology, and have a sequence that is derived from a human gelatine or collagen amino acid sequence. The invention also relates to RGD-enriched gelatines that are used for attachment to integrins. In particular The RGD-enriched gelatines of the invention are suitable for coating a cell culture support for growing anchor-dependant cell types. Further, the RGD-enriched gelatines of the invention may find use in medical applications, in particular as a coating on implant or transplant material or as a component of drug delivery systems.
摘要翻译：本发明涉及包含富含RGD的明胶的细胞支持物，其具有比在天然明胶中发生的RGD序列更均匀的分布并具有最低水平的RGD序列。更准确地说，与氨基酸总数相关的RGD序列的百分比至少为0.4，并且如果RGD富集的明胶包含350个氨基酸或更多个，则每个拉伸的350个氨基酸含有至少一个RGD基序。优选地，通过重组技术制备富含RGD的明胶，并且具有源自人明胶或胶原氨基酸序列的序列。本发明还涉及用于与整联蛋白连接的RGD富集的明胶。特别地，本发明的RGD富集的明胶适用于涂覆细胞培养支持物，用于生长锚依赖细胞类型。此外，本发明的富含RGD的明胶可用于医学应用，特别是作为植入物或移植材料上的涂层或药物递送系统的组分。

2. 发明授权

US07671016B2 RGD-enriched gelatine-like proteins with enhanced cell binding 有权
标题翻译：具有增强的细胞结合的RGD富集的明胶样蛋白质
公开(公告)号：US07671016B2
公开(公告)日：2010-03-02
申请号：US11770271
申请日：2007-06-28
申请人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
发明人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
IPC分类号： C07K14/00
CPC分类号： A61K9/5078 , A61K9/1658 , A61K47/42 , C07K14/78 , C12N5/0075 , C12N2533/30 , C12N2533/54
摘要： The invention concerns a cell support comprising an RGD-enriched gelatine that has a more even distribution of RGD sequences than occurring in a natural gelatine and with a minimum level of RGD sequences. More precise the percentage of RGD sequences related to the total number of amino acids is at least 0.4 and if the RGD-enriched gelatine comprises 350 amino acids or more, each stretch of 350 amino acids contains at least one RGD motif. Preferably the RGD-enriched gelatines are prepared by recombinant technology, and have a sequence that is derived from a human gelatine or collagen amino acid sequence. The invention also relates to RGD-enriched gelatines that are used for attachment to integrins. In particular The RGD-enriched gelatines of the invention are suitable for coating a cell culture support for growing anchor-dependant cell types. Further, the RGD-enriched gelatines of the invention may find use in medical applications, in particular as a coating on implant or transplant material or as a component of drug delivery systems.
摘要翻译：本发明涉及包含富含RGD的明胶的细胞支持物，其具有比在天然明胶中发生的RGD序列更均匀的分布并具有最低水平的RGD序列。更准确地说，与氨基酸总数相关的RGD序列的百分比至少为0.4，并且如果RGD富集的明胶包含350个氨基酸或更多个，则每个拉伸的350个氨基酸含有至少一个RGD基序。优选地，通过重组技术制备富含RGD的明胶，并且具有源自人明胶或胶原氨基酸序列的序列。本发明还涉及用于与整联蛋白连接的RGD富集的明胶。特别地，本发明的RGD富集的明胶适用于涂覆细胞培养支持物，用于生长锚依赖细胞类型。此外，本发明的富含RGD的明胶可用于医学应用，特别是作为植入物或移植材料上的涂层或药物递送系统的组分。

3. 发明授权

US06627667B2 Process for preparing a modified polymer 失效
标题翻译：制备改性聚合物的方法
公开(公告)号：US06627667B2
公开(公告)日：2003-09-30
申请号：US09898723
申请日：2001-07-03
申请人： Sebastianus Gerardus J. M. Kluijtmans , Jan Bastiaan Bouwstra , Yuzo Toda
发明人： Sebastianus Gerardus J. M. Kluijtmans , Jan Bastiaan Bouwstra , Yuzo Toda
IPC分类号： C08J520
CPC分类号： G03C1/053 , C08B15/06 , C08H1/06 , G03C1/04 , G03C1/047
摘要： The invention is directed to a process for modifying a water soluble polymer, said process comprising modifying a polymer containing amine groups, by reacting at least one of said amine groups with activated ester, said ester being the reaction product of a carboxyl activator and the carboxyl group of a molecule R—COOH, said R-group being a functional group, to produce a reaction mixture containing a polymer, said polymer containing at least one amide group; subjecting said reaction mixture to at least ion exchange chromatography to purify said reaction mixture, said purification comprising at least partly removing the said reaction product, and/or carboxyl activator.
摘要翻译：本发明涉及一种改性水溶性聚合物的方法，所述方法包括通过使至少一种所述胺基与活性酯反应来修饰含有胺基团的聚合物，所述酯是羧基活化剂与羧基的反应产物的分子R-COOH，所述R基团是官能团，以产生含有聚合物的反应混合物，所述聚合物含有至少一个酰胺基团;将所述反应混合物至少进行离子交换色谱以纯化所述反应混合物，所述纯化包括至少部分除去所述反应产物和/或羧基活化剂。

4. 发明授权

US07645737B2 Drug delivery system comprising an RGD-enriched gelatine 有权
标题翻译：药物递送系统包含富含RGD的明胶
公开(公告)号：US07645737B2
公开(公告)日：2010-01-12
申请号：US11770197
申请日：2007-06-28
申请人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
发明人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
IPC分类号： C07K14/00
CPC分类号： A61K9/5078 , A61K9/1658 , A61K47/42 , C07K14/78 , C12N5/0075 , C12N2533/30 , C12N2533/54
摘要： The invention concerns a cell support comprising an RGD-enriched gelatine that has a more even distribution of RGD sequences than occurring in a natural gelatine and with a minimum level of RGD sequences. More precise the percentage of RGD sequences related to the total number of amino acids is at least 0.4 and if the RGD-enriched gelatine comprises 350 amino acids or more, each stretch of 350 amino acids contains at least one RGD motif. Preferably the RGD-enriched gelatines are prepared by recombinant technology, and have a sequence that is derived from a human gelatine or collagen amino acid sequence. The invention also relates to RGD-enriched gelatines that are used for attachment to integrins. In particular The RGD-enriched gelatines of the invention are suitable for coating a cell culture support for growing anchor-dependant cell types. Further, the RGD-enriched gelatines of the invention may find use in medical applications, in particular as a coating on implant or transplant material or as a component of drug delivery systems.
摘要翻译：本发明涉及包含富含RGD的明胶的细胞支持物，其具有比在天然明胶中发生的RGD序列更均匀的分布并具有最低水平的RGD序列。更准确地说，与氨基酸总数相关的RGD序列的百分比至少为0.4，并且如果RGD富集的明胶包含350个氨基酸或更多个，则每个拉伸的350个氨基酸含有至少一个RGD基序。优选地，通过重组技术制备富含RGD的明胶，并且具有源自人明胶或胶原氨基酸序列的序列。本发明还涉及用于与整联蛋白连接的RGD富集的明胶。特别地，本发明的RGD富集的明胶适用于涂覆细胞培养支持物，用于生长锚依赖细胞类型。此外，本发明的富含RGD的明胶可用于医学应用，特别是作为植入物或移植材料上的涂层或药物递送系统的组分。

5. 发明授权

US07229631B2 Preparation of oil-in-water emulsions stabilised with recombinant collagen-like material and related products 失效
标题翻译：制备用重组胶原样材料和相关产品稳定的水包油乳液
公开(公告)号：US07229631B2
公开(公告)日：2007-06-12
申请号：US10672040
申请日：2003-09-26
申请人： Joseph Hubertus Olijve , Jan Bastiaan Bouwstra , Frederik Anton Wolf De , Marc Willem Theodoor Werten , Hendrik Wouter Wisselink , Richéle Deodata Wind , Tanja Jacoba Bosch Van Den , Yuzo Toda
发明人： Joseph Hubertus Olijve , Jan Bastiaan Bouwstra , Frederik Anton Wolf De , Marc Willem Theodoor Werten , Hendrik Wouter Wisselink , Richéle Deodata Wind , Tanja Jacoba Bosch Van Den , Yuzo Toda
IPC分类号： A61K9/00
CPC分类号： G03C1/005
摘要： The invention provides oil-in-water emulsions comprising recombinant collagen-like polymer in an amount sufficient to act as stabiliser of the emulsion. The polymer is especially a polypeptide which is free of helix structure, has an isoelectric point at least 0.5 pH units removed from the pH of the oil-in-water emulsion. Furthermore, amphiphilic recombinant collagen-like polymers are provided for use in oil-in-water emulsions. The amphiphilic polymers are polar at one end as a result of a relative abundance of polar amino acids, and apolar at the other end as a result of a relative abundance of apolar amino acids.
摘要翻译：本发明提供了包含足以作为乳液稳定剂的量的重组胶原样聚合物的水包油乳液。聚合物特别是不含螺旋结构的多肽，具有从水包油乳液的pH去除至少0.5个pH单位的等电点。此外，提供两亲重组胶原样聚合物用于水包油乳剂中。由于极性氨基酸的相对丰度，两亲聚合物在一端是极性的，另一端由于非极性氨基酸的相对丰度而非极性。

6. 发明授权

US06645712B1 Oil-in-water emulsion stabilized with recombinant collagen-like material 失效
标题翻译：用重组胶原样材料稳定的水包油乳液
公开(公告)号：US06645712B1
公开(公告)日：2003-11-11
申请号：US09602459
申请日：2000-06-23
申请人： Joseph Hubertus Olijve , Jan Bastiaan Bouwstra , Frederik Anton De Wolf , Marc Willem Theodoor Werten , Hendrik Wouter Wisselink , Richéle Deodata Wind , Tanja Jacoba Van Den Bosch , Yuzo Toda
发明人： Joseph Hubertus Olijve , Jan Bastiaan Bouwstra , Frederik Anton De Wolf , Marc Willem Theodoor Werten , Hendrik Wouter Wisselink , Richéle Deodata Wind , Tanja Jacoba Van Den Bosch , Yuzo Toda
IPC分类号： G03C108
CPC分类号： G03C1/005
摘要： The invention provides oil-in-water emulsions comprising recombinant collagen-like polymer in an amount sufficient to act as stabiliser of the emulsion. The polymer is especially a polypeptide which is free of helix structure, has an isoelectric point at least 0.5 pH units removed from the pH of the oil-in-water emulsion. Furthermore, amphiphilic recombinant collagen-like polymers are provided for use in oil-in-water emulsions. The amphiphilic polymers are polar at one end as a result of a relative abundance of polar amino acids, and apolar at the other end as a result of a relative abundance of apolar amino acids,
摘要翻译：本发明提供了包含足以作为乳液稳定剂的量的重组胶原样聚合物的水包油乳液。聚合物特别是不含螺旋结构的多肽，具有从水包油乳液的pH去除至少0.5个pH单位的等电点。此外，提供两亲重组胶原样聚合物用于水包油乳剂中。由于极性氨基酸的相对丰度，两亲聚合物在一端是极性的，另一端由于非极性氨基酸的相对丰度而非极性，

7. 发明授权

US07598347B2 RGD-enriched gelatines 有权
标题翻译：富含RGD的明胶
公开(公告)号：US07598347B2
公开(公告)日：2009-10-06
申请号：US11770019
申请日：2007-06-28
申请人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
发明人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
IPC分类号： C07K14/00
CPC分类号： A61K9/5078 , A61K9/1658 , A61K47/42 , C07K14/78 , C12N5/0075 , C12N2533/30 , C12N2533/54
摘要： The invention concerns a cell support comprising an RGD-enriched gelatine that has a more even distribution of RGD sequences than occurring in a natural gelatine and with a minimum level of RGD sequences. More precise the percentage of RGD sequences related to the total number of amino acids is at least 0.4 and if the RGD-enriched gelatine comprises 350 amino acids or more, each stretch of 350 amino acids contains at least one RGD motif. Preferably the RGD-enriched gelatines are prepared by recombinant technology, and have a sequence that is derived from a human gelatine or collagen amino acid sequence. The invention also relates to RGD-enriched gelatines that are used for attachment to integrins. In particular The RGD-enriched gelatines of the invention are suitable for coating a cell culture support for growing anchor-dependant cell types. Further, the RGD-enriched gelatines of the invention may find use in medical applications, in particular as a coating on implant or transplant material or as a component of drug delivery systems.
摘要翻译：本发明涉及包含富含RGD的明胶的细胞支持物，其具有比在天然明胶中发生的RGD序列更均匀的分布并具有最低水平的RGD序列。更准确地说，与氨基酸总数相关的RGD序列的百分比至少为0.4，并且如果RGD富集的明胶包含350个氨基酸或更多个，则每个拉伸的350个氨基酸含有至少一个RGD基序。优选地，通过重组技术制备富含RGD的明胶，并且具有源自人明胶或胶原氨基酸序列的序列。本发明还涉及用于与整联蛋白连接的RGD富集的明胶。特别地，本发明的RGD富集的明胶适用于涂覆细胞培养支持物，用于生长锚依赖细胞类型。此外，本发明的富含RGD的明胶可用于医学应用，特别是作为植入物或移植材料上的涂层或药物递送系统的组分。

8. 发明授权

US07560427B2 RGD-enriched gelatine-like proteins with enhanced cell binding 有权
标题翻译：具有增强的细胞结合的RGD富集的明胶样蛋白质
公开(公告)号：US07560427B2
公开(公告)日：2009-07-14
申请号：US11770256
申请日：2007-06-28
申请人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
发明人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
IPC分类号： C07K14/00
CPC分类号： A61K9/5078 , A61K9/1658 , A61K47/42 , C07K14/78 , C12N5/0075 , C12N2533/30 , C12N2533/54
摘要： The invention concerns a cell support comprising an RGD-enriched gelatine that has a more even distribution of RGD sequences than occurring in a natural gelatine and with a minimum level of RGD sequences. More precise the percentage of RGD sequences related to the total number of amino acids is at least 0.4 and if the RGD-enriched gelatine comprises 350 amino acids or more, each stretch of 350 amino acids contains at least one RGD motif. Preferably the RGD-enriched gelatines are prepared by recombinant technology, and have a sequence that is derived from a human gelatine or collagen amino acid sequence. The invention also relates to RGD-enriched gelatines that are used for attachment to integrins. In particular The RGD-enriched gelatines of the invention are suitable for coating a cell culture support for growing anchor-dependant cell types. Further, the RGD-enriched gelatines of the invention may find use in medical applications, in particular as a coating on implant or transplant material or as a component of drug delivery systems.
摘要翻译：本发明涉及包含富含RGD的明胶的细胞支持物，其具有比在天然明胶中发生的RGD序列更均匀的分布并具有最低水平的RGD序列。更准确地说，与氨基酸总数相关的RGD序列的百分比至少为0.4，并且如果RGD富集的明胶包含350个氨基酸或更多个，则每个拉伸的350个氨基酸含有至少一个RGD基序。优选地，通过重组技术制备富含RGD的明胶，并且具有源自人明胶或胶原氨基酸序列的序列。本发明还涉及用于与整联蛋白连接的RGD富集的明胶。特别地，本发明的RGD富集的明胶适用于涂覆细胞培养支持物，用于生长锚依赖细胞类型。此外，本发明的富含RGD的明胶可用于医学应用，特别是作为植入物或移植材料上的涂层或药物递送系统的组分。

9. 发明授权

US07517954B2 RGD-enriched gelatine-like proteins with enhanced cell binding 有权
标题翻译：具有增强的细胞结合的RGD富集的明胶样蛋白质
公开(公告)号：US07517954B2
公开(公告)日：2009-04-14
申请号：US10550786
申请日：2004-03-26
申请人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
发明人： Jan Bastiaan Bouwstra , Andries Johannes Jozef Van Es , Yuzo Toda
IPC分类号： C07K14/00
CPC分类号： A61K9/5078 , A61K9/1658 , A61K47/42 , C07K14/78 , C12N5/0075 , C12N2533/30 , C12N2533/54
摘要： The invention concerns a cell support comprising an RGD-enriched gelatine that has a more even distribution of RGD sequences than occurring in a natural gelatine and with a minimum level of RGD sequences. More precise the percentage of RGD sequences related to the total number of amino acids is at least 0.4 and if the RGD-enriched gelatine comprises 350 amino acids or more, each stretch of 350 amino acids contains at least one RGD motif. Preferably the RGD-enriched gelatines are prepared by recombinant technology, and have a sequence that is derived from a human gelatine or collagen amino acid sequence. The invention also relates to RGD-enriched gelatines that are used for attachment to integrins. In particular The RGD-enriched gelatines of the invention are suitable for coating a cell culture support for growing anchor dependant cell types. Further, the RGD-enriched gelatines of the invention may find use in medical applications, in particular as a coating on implant or transplant material or as a component of drug delivery systems.
摘要翻译：本发明涉及包含富含RGD的明胶的细胞支持物，其具有比在天然明胶中发生的RGD序列更均匀的分布并具有最低水平的RGD序列。更准确地说，与氨基酸总数相关的RGD序列的百分比至少为0.4，并且如果RGD富集的明胶包含350个氨基酸或更多个，则每个拉伸的350个氨基酸含有至少一个RGD基序。优选地，通过重组技术制备富含RGD的明胶，并且具有源自人明胶或胶原氨基酸序列的序列。本发明还涉及用于与整联蛋白连接的RGD富集的明胶。特别地，本发明的RGD富集的明胶适用于涂覆细胞培养支持物，用于生长锚定依赖细胞类型。此外，本发明的富含RGD的明胶可用于医学应用，特别是作为植入物或移植材料上的涂层或药物递送系统的组分。

10. 发明授权

US07192926B2 Use of recombinant gelatin-like proteins as plasma expanders and compositions suitable for plasma substitution 失效
标题翻译：使用重组明胶样蛋白作为血浆扩张剂和适合于血浆置换的组合物
公开(公告)号：US07192926B2
公开(公告)日：2007-03-20
申请号：US10658989
申请日：2003-09-10
申请人： Jan Bastiaan Bouwstra , Yuzo Toda
发明人： Jan Bastiaan Bouwstra , Yuzo Toda
IPC分类号： A61K38/16 , C07H21/04
CPC分类号： C07K14/78 , A61K38/00
摘要： The invention relates to compositions suitable for plasma substitution comprising as a plasma expander a recombinant gelatin-like protein. Characteristic is that the gelatin-like protein can be a monomer or a polymer like a dimer, trimer or a tetramer of a human recombinant gelatin-like protein having an isolectric point of less than 8. The resulting gelatin-like proteins provide a method to control the clearance rate of a plasma expander by its molecular weight. Preferably the gelatin-like proteins have a low hydroxyproline content which prevents the composition from gelling and thus allows the use of high-molecular weight proteins in order to establish a suitable colloid osmotic pressure. An additional advantage of the gelatin-like proteins is that these avoid the risk of anaphylactic shock that exists in conjunction with the use of commercially available preparations.
摘要翻译：本发明涉及适用于血浆置换的组合物，其包含作为血浆扩张剂的重组明胶样蛋白。特征在于，明胶样蛋白质可以是单体或聚合物，如具有小于8的等电点的人重组明胶样蛋白质的二聚体，三聚体或四聚体。所得明胶样蛋白质提供了一种方法，通过分子量控制等离子体膨胀机的清除率。优选地，明胶样蛋白质具有低羟脯氨酸含量，其防止组合物胶凝，因此允许使用高分子量蛋白质以建立合适的胶体渗透压。明胶样蛋白质的另外的优点是这些避免了与使用市售制剂一起存在的过敏性休克的风险。

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