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    METHOD OF CULTURING VIABLE CELLS AND METHOD OF REGULATING THE LEVEL OF A COMPOUND IN A BODY FLUID
    1.
    发明申请
    METHOD OF CULTURING VIABLE CELLS AND METHOD OF REGULATING THE LEVEL OF A COMPOUND IN A BODY FLUID 审中-公开
    培养可见细胞的方法和调节体液中化合物水平的方法

    公开(公告)号：WO1993022427A1

    公开(公告)日：1993-11-11

    申请号：PCT/US1993003843

    申请日：1993-04-23

    Applicant: SOMATIX THERAPY CORPORATION ,  THE POLYMER TECHNOLOGY GROUP, INC.

    Inventor： SOMATIX THERAPY CORPORATION ,  THE POLYMER TECHNOLOGY GROUP, INC. ,  WARD, Robert, S. ,  MONAHAN, John ,  KUHN, Robert

    IPC: C12N05/08

    CPC classification number: A61K9/0092 ,  A61F2/022 ,  A61L27/3804 ,  A61L27/3895 ,  C08G18/12 ,  C08G18/4808 ,  C08G18/6674 ,  C12N5/0068 ,  C12N2533/30 ,  C08G18/3228 ,  C08G18/2865

    Abstract: A method of culturing live viable cells comprises culturing the cells under the conditions effective for cells to survive in the presence of a non-porous, semi-permeable biocompatible film of predefined characteristics having a tensile strength of 350-10,000 psi, an ultimate elongation of 300-1,500 %, a water absorption such that the sum of the volume fraction of absorbed water in the hydrophilic volume fraction of the soft segment is 100-2,000 % of the dried polymer volume and 50-95 % of the wet polymer volume. The film permeability can be changed to have different cut-off molecular weights while being substantially impermeable to cells and particulate matter as well as high molecular weight molecules. A method of regulating the level of a compound in a body fluid of the subject afflicted with an endogenous defect resulting in abnormal levels of the compound in the body fluid, in the substantial absence of a detrimental immunological reaction comprises: enclosing cells lacking the endogenous defect of the patient's cells in a biocompatible, implantable device, wherein at least one portion thereof comprises a non-porous, semi-permeable, biocompatible film substantially enclosing the cells, the film formed from a copolymer comprising about 5 to 45 wt% of at least one hard segment, and about 95 to 55 wt% of at least one soft segment comprising at least one hydrophilic, hydrophobic or amphipathic oligomer selected from the group consisting of aliphatic polyols, aliphatic and aromatic polyamines and mixtures thereof; the film having a tensile strength greater than about 350 psi and up to about 10,000 psi, an ultimate elongation greater than about 300 % and up to about 1,500 % and a water absorption such that the sum of the volume fraction of absorbed water and the hydrophilic volume fraction of the soft segment exceeds about 100 % and up to about 2,000 % of the dry polymer volume and exceeds about 50 % and up to about 95 % of the wet polymer volume, and the film being permeable to molecules of up to about 6,000 to 600,000 molecular weight and substantially impermeable to cells and particulate matter; implanting the device comprising the cells into a site in the subject's body where the cells are in contact with the subject's body fluid; and allowing the cells to grow at the implantation site where they are in direct interactive contact with the compound and act to regulate its level in the body fluid.

    Abstract translation: 培养活细胞的方法包括在有效使细胞存活的条件下培养细胞，所述条件是在具有350-10,000psi拉伸强度的预定特征的无孔半透性生物相容性薄膜存在下， 300-1,500％的吸水率，使得软链段的亲水体积分数中吸收水的体积分数之和为干燥聚合物体积的100-2,000％，湿聚合物体积的50-95％。 膜的渗透性可以改变为具有不同的截止分子量，同时对细胞和颗粒物质以及高分子量分子基本上是不可渗透的。 在基本上不存在有害的免疫反应的情况下，调节患有体内缺陷导致体液中化合物异常水平的内源性缺陷的受试者的体液中的化合物的水平的方法包括：包含缺乏内源性缺陷的细胞 的生物相容性可植入装置，其中至少一部分包含基本上封闭细胞的非多孔，半渗透的生物相容性膜，所述膜由共聚物形成，所述共聚物包含至少约5至45重量％的至少 约95至55重量％的至少一个软链段，其包含至少一种选自脂族多元醇，脂族和芳族多胺及其混合物的亲水性，疏水性或两亲性低聚物; 该膜的拉伸强度大于约350psi且高达约10,000psi，极限伸长率大于约300％且高达约1500％，并且吸水率使得吸收的水的体积分数和亲水性的总和 软链段的体积分数超过干聚合物体积的约100％且高达约2,000％，并且超过湿聚合物体积的约50％且高达约95％，并且该膜可渗透至高达约6,000 至60万分子量，对细胞和颗粒物质基本不渗透; 将包含细胞的装置植入受试者体内与受试者体液接触的部位; 并且允许细胞在植入部位生长，在那里它们与化合物直接相互接触并起作用以调节其体液中的水平。

    BIOCOMPATIBLE, THERAPEUTIC, IMPLANTABLE DEVICE
    5.
    发明申请
    BIOCOMPATIBLE, THERAPEUTIC, IMPLANTABLE DEVICE 审中-公开
    生物化学，治疗，可植入的装置

    公开(公告)号：WO1993021902A1

    公开(公告)日：1993-11-11

    申请号：PCT/US1993003850

    申请日：1993-04-23

    Applicant: SOMATIX THERAPY CORPORATION ,  THE POLYMER TECHNOLOGY GROUP, INC.

    Inventor： SOMATIX THERAPY CORPORATION ,  THE POLYMER TECHNOLOGY GROUP, INC. ,  WARD, Robert, S. ,  CHATER, Veronica, Jean ,  KUHN, Robert

    IPC: A61K09/00

    CPC classification number: A61K9/0024 ,  A61F2/022

    Abstract: This invention relates to an implantable, biocompatible device possessing at least one cavity within which live cells can be introduced and maintained such that when the device is implanted into a subject, the cells are in continuous interaction with the subject's bodily fluids to provide a therapeutic or prophylactic effect to the subject that requires a direct interactive contact with the body's fluids, wherein at least one portion of the outside thereof comprises a non-porous, semi-permeable, biocompatible film formed from a copolymer comprising about 5 to 45 wt % of at least one hard segment, and about 95 to 55 wt % of at least one soft segment, substantially impermeable to cells and particulate matter. Multiple embodiments of the device of this invention are provided.

    Abstract translation: 本发明涉及一种可植入的生物相容性装置，其具有至少一个空腔，活细胞可以在该空腔内引入和保持，使得当将该装置植入受试者时，细胞与受试者的体液持续相互作用以提供治疗或 需要与身体流体直接交互接触的对象的预防效果，其中至少一部分外部包含由共聚物形成的非多孔，半渗透的生物相容性膜，所述共聚物包含约5至45重量％的 至少一个硬链段，以及约95至55wt％的至少一个软链段，对细胞和颗粒物质基本上不可渗透。 提供了本发明的设备的多个实施例。

    JOINT EXPRESSION OF GTP CYCLOHYDROLASE AND TYROSINE HYDROXYLASE
    10.
    发明申请
    JOINT EXPRESSION OF GTP CYCLOHYDROLASE AND TYROSINE HYDROXYLASE 审中-公开
    GTP环糊精和酪氨酸羟化酶的联合表达

    公开(公告)号：WO1997018319A1

    公开(公告)日：1997-05-22

    申请号：PCT/US1996017696

    申请日：1996-11-01

    Applicant: SOMATIX THERAPY CORPORATION

    Inventor： SOMATIX THERAPY CORPORATION ,  LEFF, Stuart, E. ,  MANDEL, Ron

    IPC: C12N15/86

    CPC classification number: C12N9/0071 ,  A61K38/00 ,  A61K48/00 ,  C12N9/78

    Abstract: The invention provides novel genetically modified host cells, vectors, and methods for the treatment of Parkinson's disease and other related disease conditions in which the dopamine production is deficient. The invention relates to the surprising discovery that coexpression of tyrosine hydroxylase and GTP cyclohydrolase enables host cells to produce elevated dopamine and L-DOPA without adding tetrahydrobiopterin and that the coexpression of GTP cyclohydrolase stabilizes tyrosine hydroxylase. One embodiment of the invention is genetically modified host cells containing heterologous polynucleotide sequences encoding and capable of expressing GTP cyclohydrolase and tyrosine hydroxylase. Other embodiments of the invention include genetic construction that contain and can simultaneously express polynucleotide sequences encoding a GTP cyclohydrolase and a tyrosine hydroxylase. The invention also provides methods of producing L-DOPA or dopamine using the host cells of the invention. The invention also provides methods of treating patients of Parkinson's disease or other diseases related to a dopamine production deficiency using the vectors and methods of the invention.

    Abstract translation: 本发明提供了新型遗传修饰的宿主细胞，载体和用于治疗帕金森病和多巴胺生产缺乏的其他相关疾病状况的方法。 本发明涉及令​​人惊奇的发现：酪氨酸羟化酶和GTP环化水解酶的共表达能够使宿主细胞在不添加四氢生物蝶呤的情况下产生升高的多巴胺和L-DOPA，并且GTP环化水解酶的共表达稳定了酪氨酸羟化酶。 本发明的一个实施方案是含有编码并能够表达GTP环化水解酶和酪氨酸羟化酶的异源多核苷酸序列的遗传修饰宿主细胞。 本发明的其它实施方案包括含有并可以同时表达编码GTP环化水解酶和酪氨酸羟化酶的多核苷酸序列的遗传构建。 本发明还提供使用本发明的宿主细胞产生L-DOPA或多巴胺的方法。 本发明还提供了使用本发明的载体和方法治疗帕金森病患者或与多巴胺生产缺乏相关的其它疾病的方法。

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