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    POLYHYDROXYALKANOATES FOR IN VIVO APPLICATIONS
    21.
    发明申请
    POLYHYDROXYALKANOATES FOR IN VIVO APPLICATIONS 有权
    用于生殖器官应用的聚羟基烷酸酯

    公开(公告)号：US20110135707A1

    公开(公告)日：2011-06-09

    申请号：US13021419

    申请日：2011-02-04

    申请人： Simon F. Williams ,  David P. Martin ,  Tillman Gerngross ,  Daniel M. Horowitz

    发明人： Simon F. Williams ,  David P. Martin ,  Tillman Gerngross ,  Daniel M. Horowitz

    IPC分类号： A61F2/28 ,  C12N5/07 ,  A61F2/00 ,  A61K9/00 ,  A61K49/00 ,  A61K38/02 ,  A61K31/7088 ,  A61K31/715 ,  A61K31/70 ,  A61K31/20 ,  A61K9/70 ,  A61P17/02 ,  A61P19/08 ,  A61P9/00 ,  C08G63/91 ,  B32B1/08

    CPC分类号： C12P7/625 ,  A61B17/06166 ,  A61B42/00 ,  A61K47/593 ,  A61K47/6957 ,  A61L15/26 ,  A61L17/10 ,  A61L27/18 ,  A61L27/34 ,  A61L29/06 ,  A61L31/06 ,  C08G63/06 ,  C08G63/6852 ,  C08G63/6882 ,  C08G63/912 ,  C12N5/0068 ,  C12N2533/30 ,  Y10S977/775 ,  Y10T428/139 ,  C08L67/04

    摘要： Polyhydroxyalkanoates (PHAs) from which pyrogen has been removed are provided for use in numerous biomedical applications. PHAs which have been chemically modified to enhance physical and/or chemical properties, for targeting or to modify biodegradability or clearance by the reticuloendothelial system (RES), are described. Methods for depyrogenating PHA polymers prepared by bacterial fermentation processes are also provided, wherein pyrogens are removed from the polymers without adversely impacting the polymers' inherent chemical structures and physical properties. PHAs with advantageous processing characteristics, including low melting points and/or solubility in non-toxic solvents, are also described. PHAs are provided which are suitable for use in in vivo applications such as in tissue coatings, stents, sutures, tubing, bone and other prostheses, bone or tissue cements, tissue regeneration devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses. Properties which are selected for include degradability, elasticity, inclusion of functional groups or derivatized groups, which can in turn be used to attach targeting agents, and bioadhesion.

    摘要翻译： 已经除去热原的聚羟基链烷酸酯（PHA）被提供用于许多生物医学应用。 已经化学改性以增强物理和/或化学性质的PHA用于通过网状内皮系统（RES）靶向或修饰生物降解性或清除的PHA。 还提供了通过细菌发酵方法制备的PHA聚合物去热原化方法，其中热原从聚合物中除去而不会不利地影响聚合物固有的化学结构和物理性质。 还描述了具有有利处理特性的PHA，包括低熔点和/或在无毒溶剂中的溶解度。 提供适用于体内应用的PHA，例如在组织涂层，支架，缝线，管，骨和其他假体，骨或组织水泥，组织再生装置，伤口敷料，药物递送以及用于诊断和预防用途 。 选择的性质包括降解性，弹性，包含官能团或衍生基团，其又可用于附着靶向剂，以及生物粘附。

    ARG1, ARG2, ARG3, HIS1, HIS2, HIS5, HIS6 genes and methods for stable genetic integration
    22.
    发明授权
    ARG1, ARG2, ARG3, HIS1, HIS2, HIS5, HIS6 genes and methods for stable genetic integration 失效
    ARG1，ARG2，ARG3，HIS1，HIS2，HIS5，HIS6基因和稳定遗传整合的方法

    公开(公告)号：US07479389B2

    公开(公告)日：2009-01-20

    申请号：US11071690

    申请日：2005-03-02

    申请人： Juergen Nett ,  Tillman Gerngross

    发明人： Juergen Nett ,  Tillman Gerngross

    IPC分类号： C12N15/74 ,  C12N15/00 ,  C12P21/00 ,  C12N1/19 ,  C07K14/00 ,  C07H21/00

    CPC分类号： C12N15/52 ,  C12N15/81

    摘要： Novel genes encoding P. pastoris ARG1, ARG2, ARG3, HIS1, HIS2, HIS5 and HIS6 are disclosed. A method for inactivating alternately at least two biosynthetic pathways in a methylotrophic yeast is provided. A method for producing and selecting yeast strains characterized as being capable of genetic integration of heterologous sequences into the host genome using the genes involved in the biosynthetic pathways is also disclosed.

    摘要翻译： 公开了编码巴斯德毕赤酵母ARG1，ARG2，ARG3，HIS1，HIS2，HIS5和HIS6的新型基因。 提供了在甲基营养酵母中交替灭活至少两种生物合成途径的方法。 还公开了用于生产和选择酵母菌株的方法，其特征在于能够使用参与生物合成途径的基因将异源序列遗传整合到宿主基因组中。

    Method of forming medical devices having pyrogen removed for in vivo application
    25.
    发明授权
    Method of forming medical devices having pyrogen removed for in vivo application 有权
    形成用于体内应用除去热原的医疗装置的方法

    公开(公告)号：US08231889B2

    公开(公告)日：2012-07-31

    申请号：US13021419

    申请日：2011-02-04

    申请人： Simon F. Williams ,  David P. Martin ,  Tillman Gerngross ,  Daniel M. Horowitz

    发明人： Simon F. Williams ,  David P. Martin ,  Tillman Gerngross ,  Daniel M. Horowitz

    IPC分类号： A61F2/00 ,  A61F13/00 ,  C12P7/62 ,  C12P1/04 ,  C12N11/08 ,  C12N11/04 ,  C12N5/07

    CPC分类号： C12P7/625 ,  A61B17/06166 ,  A61B42/00 ,  A61K47/593 ,  A61K47/6957 ,  A61L15/26 ,  A61L17/10 ,  A61L27/18 ,  A61L27/34 ,  A61L29/06 ,  A61L31/06 ,  C08G63/06 ,  C08G63/6852 ,  C08G63/6882 ,  C08G63/912 ,  C12N5/0068 ,  C12N2533/30 ,  Y10S977/775 ,  Y10T428/139 ,  C08L67/04

    摘要： Polyhydroxyalkanoates (PHAs) from which pyrogen has been removed are provided for use in numerous biomedical applications. PHAs which have been chemically modified to enhance physical and/or chemical properties, for targeting or to modify biodegradability or clearance by the reticuloendothelial system (RES), are described. Methods for depyrogenating PHA polymers prepared by bacterial fermentation processes are also provided, wherein pyrogens are removed from the polymers without adversely impacting the polymers' inherent chemical structures and physical properties. PHAs with advantageous processing characteristics, including low melting points and/or solubility in non-toxic solvents, are also described. PHAs are provided which are suitable for use in in vivo applications such as in tissue coatings, stents, sutures, tubing, bone and other prostheses, bone or tissue cements, tissue regeneration devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses. Properties which are selected for include degradability, elasticity, inclusion of functional groups or derivatized groups, which can in turn be used to attach targeting agents, and bioadhesion.

    摘要翻译： 已经除去热原的聚羟基链烷酸酯（PHA）被提供用于许多生物医学应用。 已经化学改性以增强物理和/或化学性质的PHA用于通过网状内皮系统（RES）靶向或修饰生物降解性或清除的PHA。 还提供了通过细菌发酵方法制备的PHA聚合物去热原化方法，其中热原从聚合物中除去而不会不利地影响聚合物固有的化学结构和物理性质。 还描述了具有有利处理特性的PHA，包括低熔点和/或在无毒溶剂中的溶解度。 提供适用于体内应用的PHA，例如在组织涂层，支架，缝线，管，骨和其他假体，骨或组织水泥，组织再生装置，伤口敷料，药物递送以及用于诊断和预防用途 。 选择的性质包括降解性，弹性，包含官能团或衍生基团，其又可用于附着靶向剂，以及生物粘附。

    ARG1, ARG2, ARG3, HIS1, HIS2, HIS5, HIS6 genes and methods for stable genetic integration
    26.
    发明申请
    ARG1, ARG2, ARG3, HIS1, HIS2, HIS5, HIS6 genes and methods for stable genetic integration 失效
    ARG1，ARG2，ARG3，HIS1，HIS2，HIS5，HIS6基因和稳定遗传整合的方法

    公开(公告)号：US20070072262A1

    公开(公告)日：2007-03-29

    申请号：US11071690

    申请日：2005-03-02

    申请人： Juergen Nett ,  Tillman Gerngross

    发明人： Juergen Nett ,  Tillman Gerngross

    IPC分类号： C07H21/04 ,  C12P21/06 ,  C12N9/10 ,  C12N9/64

    CPC分类号： C12N15/52 ,  C12N15/81

    摘要： Novel genes encoding P. pastoris ARG1, ARG2, ARG3, HIS1, HIS2, HIS5 and HIS6 are disclosed. A method for inactivating alternately at least two biosynthetic pathways in a methylotrophic yeast is provided. A method for producing and selecting yeast strains characterized as being capable of genetic stable integration of heterologous sequences into the host genome using the genes involved in the biosynthetic pathways is also disclosed.

    摘要翻译： 公开了编码巴斯德毕赤酵母ARG1，ARG2，ARG3，HIS1，HIS2，HIS5和HIS6的新型基因。 提供了在甲基营养酵母中交替灭活至少两种生物合成途径的方法。 还公开了生产和选择酵母菌株的方法，其特征在于能够使用参与生物合成途径的基因将异源序列遗传稳定整合到宿主基因组中。

    Method for producing modified glycoproteins
    27.
    发明申请
    Method for producing modified glycoproteins 审中-公开
    生产改性糖蛋白的方法

    公开(公告)号：US20070105127A1

    公开(公告)日：2007-05-10

    申请号：US11271217

    申请日：2005-11-10

    申请人： Tillman Gerngross

    发明人： Tillman Gerngross

    IPC分类号： C40B30/06 ,  C40B40/08

    CPC分类号： C12P21/005 ,  C07K2319/04 ,  C07K2319/05 ,  C12N1/14 ,  C12N9/1048 ,  C12N9/2488 ,  C12N15/79 ,  C12N15/80 ,  C12N15/81 ,  C12Y302/01 ,  C12Y302/01113

    摘要： Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways. This is achieved using a combination of engineering and/or selection of strains which: do not express certain enzymes which create the undesirable complex structures characteristic of the fungal glycoproteins, which express exogenous enzymes selected either to have optimal activity under the conditions present in the fungi where activity is desired, or which are targeted to an organelle where optimal activity is achieved, and combinations thereof wherein the genetically engineered eukaryote expresses multiple exogenous enzymes required to produce “human-like” glycoproteins.

    摘要翻译： 已经开发了具有遗传修饰的糖基化途径的细胞系，其允许它们进行模拟人类中糖蛋白的加工的酶反应序列。 在这些工程化宿主中表达的重组蛋白可以产生与其对应物更相似的糖蛋白（如果基本上不相同）。 通常产生含有高甘露糖的N-聚糖（包括单细胞和多细胞真菌）的低等真核生物被修饰以产生N-聚糖，例如Man 3或GlcNAc 2 N或其它结构 沿着人类糖基化途径。 这是使用以下工程和/或选择的组合实现的：不表达产生真菌糖蛋白特征的不合需要的复合结构的某些酶，其表达选择在真菌中存在的条件下具有最佳活性的外源酶 其中需要活性或靶向实现最佳活性的细胞器，以及其组合，其中遗传工程真核生物表达产生“人样”糖蛋白所需的多种外源酶。

    Methods for producing modified glycoproteins
    28.
    发明申请
    Methods for producing modified glycoproteins 有权

    公开(公告)号：US20060177898A1

    公开(公告)日：2006-08-10

    申请号：US11249061

    申请日：2005-10-11

    申请人： Tillman Gerngross

    发明人： Tillman Gerngross

    IPC分类号： C12P21/06 ,  C12N1/18 ,  C12N1/16 ,  C12N15/74 ,  C12N9/24 ,  C12N9/10

    CPC分类号： C12P21/005 ,  C07K2319/04 ,  C07K2319/05 ,  C12N1/14 ,  C12N9/1048 ,  C12N9/2488 ,  C12N15/79 ,  C12N15/80 ,  C12N15/81 ,  C12Y302/01 ,  C12Y302/01113

    摘要： Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways. This is achieved using a combination of engineering and/or selection of strains which: do not express certain enzymes which create the undesirable complex structures characteristic of the fungal glycoproteins, which express exogenous enzymes selected either to have optimal activity under the conditions present in the fungi where activity is desired, or which are targeted to an organelle where optimal activity is achieved, and combinations thereof wherein the genetically engineered eukaryote expresses multiple exogenous enzymes required to produce “human-like” glycoproteins.

    Methods for producing modified glycoproteins
    29.
    发明申请
    Methods for producing modified glycoproteins 有权

    公开(公告)号：US20060078963A1

    公开(公告)日：2006-04-13

    申请号：US11240432

    申请日：2005-09-30

    申请人： Tillman Gerngross

    发明人： Tillman Gerngross

    IPC分类号： C12P21/06 ,  C12N9/10 ,  C07K14/47

    CPC分类号： C12P21/005 ,  C07K2319/04 ,  C07K2319/05 ,  C12N1/14 ,  C12N9/1048 ,  C12N9/2488 ,  C12N15/79 ,  C12N15/80 ,  C12N15/81 ,  C12Y302/01 ,  C12Y302/01113

    摘要： Cell lines having genetically modified glycosylation pathways that allow them to carry out a sequence of enzymatic reactions, which mimic the processing of glycoproteins in humans, have been developed. Recombinant proteins expressed in these engineered hosts yield glycoproteins more similar, if not substantially identical, to their human counterparts. The lower eukaryotes, which ordinarily produce high-mannose containing N-glycans, including unicellular and multicellular fungi are modified to produce N-glycans such as Man5GlcNAc2 or other structures along human glycosylation pathways. This is achieved using a combination of engineering and/or selection of strains which: do not express certain enzymes which create the undesirable complex structures characteristic of the fungal glycoproteins, which express exogenous enzymes selected either to have optimal activity under the conditions present in the fungi where activity is desired, or which are targeted to an organelle where optimal activity is achieved, and combinations thereof wherein the genetically engineered eukaryote expresses multiple exogenous enzymes required to produce “human-like” glycoproteins.

    Removing endotoxin with an oxdizing agent from polyhydroxyalkanoates produced by fermentation
    30.
    发明授权
    Removing endotoxin with an oxdizing agent from polyhydroxyalkanoates produced by fermentation 失效
    用氧化剂从发酵产生的聚羟基链烷酸酯中去除内毒素

    公开(公告)号：US06245537B1

    公开(公告)日：2001-06-12

    申请号：US09076198

    申请日：1998-05-12

    申请人： Simon F. Williams ,  David P. Martin ,  Tillman Gerngross ,  Daniel M. Horowitz

    发明人： Simon F. Williams ,  David P. Martin ,  Tillman Gerngross ,  Daniel M. Horowitz

    IPC分类号： C12P762

    CPC分类号： C12P7/625 ,  A61B17/06166 ,  A61B42/00 ,  A61K47/593 ,  A61K47/6957 ,  A61L15/26 ,  A61L17/10 ,  A61L27/18 ,  A61L27/34 ,  A61L29/06 ,  A61L31/06 ,  C08G63/06 ,  C08G63/6852 ,  C08G63/6882 ,  C08G63/912 ,  C12N5/0068 ,  C12N2533/30 ,  Y10S977/775 ,  Y10T428/139 ,  C08L67/04

    摘要： Polyhydroxyalkanoate (PHA) that contains a pyrogen such as endotoxin due to a process of producing the PHA is treated to remove the pyrogen by a process that does not affect the inherent chemical and physical properties of the PHA to obtain a biocompatible PHA. PHA produced by fermentation with a Gram negative bacteria can be treated with an oxidizing agent such as hydrogen peroxide or benzoyl peroxide to reduce the endotoxin content to less than 20 endotoxin units/gram of PHA to produce PHA that does not elicit an acute inflammatory response when implanted in an animal. The PHA may have a melting point or glass transition temperature less than 136° C., and can be chemically modified or derivatized such as by covalently coupling an attachment or targeting molecule. The PHA may be used to form various medical devices, and can be used for in vivo applications including tissue coatings, stents, sutures, tubing, bone and other prostheses, bone and tissue cements, tissue regenerating devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses.

    摘要翻译： 处理由于产生PHA的过程而含有热原如内毒素的聚羟基链烷酸酯（PHA），以通过不影响PHA固有的化学和物理性能以获得生物相容性PHA的方法除去热原。 通过用革兰氏阴性细菌发酵产生的PHA可以用氧化剂如过氧化氢或过氧化苯甲酰处理以将内毒素含量降低到小于20个内毒素单位/克的PHA，以产生不引起急性炎症反应的PHA 植入动物。 PHA可以具有低于136℃的熔点或玻璃化转变温度，并且可以通过共价偶联附着物或靶向分子进行化学修饰或衍生化。 PHA可以用于形成各种医疗装置，并且可以用于体内应用，包括组织涂层，支架，缝线，管，骨和其他假体，骨和组织水泥，组织再生装置，伤口敷料，药物递送和 用于诊断和预防用途。