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    Delivery of therapeutic biologicals from implantable tissue matrices
    1.
    发明授权
    Delivery of therapeutic biologicals from implantable tissue matrices 失效
    从可植入组织基质递送治疗性生物学

    公开(公告)号：US07078032B2

    公开(公告)日：2006-07-18

    申请号：US10690077

    申请日：2003-10-21

    申请人： David T. MacLaughlin ,  Joseph P. Vacanti ,  Patricia K. Donahoe ,  Peter T. Masiakos

    发明人： David T. MacLaughlin ,  Joseph P. Vacanti ,  Patricia K. Donahoe ,  Peter T. Masiakos

    IPC分类号： A61K48/00 ,  A61K9/14 ,  A01N63/00 ,  C12N5/00 ,  C12N15/63 ,  C12P21/06 ,  C12N15/00

    CPC分类号： C12N5/0656 ,  A61K38/22 ,  A61K48/00 ,  B33Y10/00 ,  B33Y30/00 ,  B33Y70/00 ,  B33Y80/00 ,  C12N2510/02

    摘要： Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin™, interferons, and anti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells. Matrices can be formed of synthetic or natural materials, by chemical coupling at the time of implantation, using standard techniques for formation of fibrous matrices from polymeric fibers, and using micromachining or microfabrication techniques. These devices and strategies are used as delivery systems via standard or minimally invasive implantation techniques for any number of parenterally deliverable recombinant proteins, particularly those that are difficult to produce in large amounts and/or active forms using conventional methods of purification, for the treatment of a variety of conditions.

    摘要翻译： 正常细胞如成纤维细胞或其它组织或器官细胞类型被遗传工程化以表达生物活性的治疗剂，例如通常少量产生的蛋白质，例如MIS或TGF-β家族的其他成员 赫赛汀（Herceptin TM），干扰素和抗血管生成因子。 将这些细胞接种到基质中以便植入待治疗的患者中。 细胞还可以被设计成包括致死基因，使得植入的细胞一旦完成就可以被破坏。 细胞可以植入各种不同的基质中。 在优选的实施方案中，当细胞移植以形成产生所需生物活性剂的功能组织时，这些基质可植入和生物降解的时间等于或小于预期的治疗期。 植入可能是异位的或在某些情况下是原位的。 代表性的细胞类型包括组织特异性细胞，祖细胞和干细胞。 矩阵可以由合成或天然材料形成，通过植入时的化学偶联，使用从聚合物纤维形成纤维基质的标准技术，以及使用微加工或微细加工技术。 这些装置和策略通过标准或微创植入技术用于任何数量的肠胃外可输送的重组蛋白质，特别是使用常规的纯化方法难以大量和/或活性形式生产的装置和策略，用于治疗 各种条件。

    Delivery of therapeutic biologicals from implantable tissue matrices
    2.
    发明授权
    Delivery of therapeutic biologicals from implantable tissue matrices 失效

    公开(公告)号：US06692738B2

    公开(公告)日：2004-02-17

    申请号：US09770339

    申请日：2001-01-26

    申请人： David T. MacLaughlin ,  Joseph P. Vacanti ,  Patricia K. Donahoe ,  Peter T. Masiakos

    发明人： David T. MacLaughlin ,  Joseph P. Vacanti ,  Patricia K. Donahoe ,  Peter T. Masiakos

    IPC分类号： A61K4800

    CPC分类号： C12N5/0656 ,  A61K38/22 ,  A61K48/00 ,  B33Y10/00 ,  B33Y30/00 ,  B33Y70/00 ,  B33Y80/00 ,  C12N2510/02

    摘要： Normal cells, such as fibroblasts or other tissue or organ cell types, are genetically engineered to express biologically active, therapeutic agents, such as proteins that are normally produced in small amounts, for example, MIS, or other members of the TGF-beta family Herceptin™, interferons, andanti-angiogenic factors. These cells are seeded into a matrix for implantation into the patient to be treated. Cells may also be engineered to include a lethal gene, so that implanted cells can be destroyed once treatment is completed. Cells can be implanted in a variety of different matrices. In a preferred embodiment, these matrices are implantable and biodegradable over a period of time equal to or less than the expected period of treatment, when cells engraft to form a functional tissue producing the desired biologically active agent. Implantation may be ectopic or in some cases orthotopic. Representative cell types include tissue specific cells, progenitor cells, and stem cells. Matrices can be formed of synthetic or natural materials, by chemical coupling at the time of implantation, using standard techniques for formation of fibrous matrices from polymeric fibers, and using micromachining or microfabrication techniques. These devices and strategies are used as delivery systems via standard or minimally invasive implantation techniques for any number of parenterally deliverable recombinant proteins, particularly those that are difficult to produce in large amounts and/or active forms using conventional methods of purification, for the treatment of a variety of conditions that produce abnormal growth, including treatment of malignant and benign neoplasias, vascular malformations (hemangiomas), inflammatory conditions, keloid formation, abdominal or plural adhesions, endometriosis, congenital or endocrine abnormalities, and other conditions that can produce abnormal growth such as infection. Efficacy of treatment with the therapeutic biologicals is detected by determining specific criteria, for example, cessation of cell proliferation, regression of abnormal tissue, or cell death, or expression of genes or proteins reflecting the above.

    OVARIAN CANCER STEM CELLS AND METHODS OF ISOLATION AND USES THEREOF
    5.
    发明申请
    OVARIAN CANCER STEM CELLS AND METHODS OF ISOLATION AND USES THEREOF 有权
    卵巢癌干细胞及其分离方法及其用途

    公开(公告)号：US20140194366A1

    公开(公告)日：2014-07-10

    申请号：US14123551

    申请日：2012-06-01

    申请人： Patricia K. Donahoe ,  David T. MacLaughlin ,  Jose Teixeira

    发明人： Patricia K. Donahoe ,  David T. MacLaughlin ,  Jose Teixeira

    IPC分类号： G01N33/574

    CPC分类号： G01N33/57449 ,  A61K31/416 ,  G01N33/5073 ,  G01N2333/70585 ,  G01N2333/70596 ,  G01N2800/52

    摘要： The present invention generally relates to methods, assays, compositions and kits related to a subpopulation of ovarian cancer stem cells which are selected or enriched by chemotherapeutic agents and inhibited by MIS (Mullerian Inhibiting Substance) and MIS mimetics. In particular, the present invention relates to a population of CD44+/CD24+/EpCam+/ECad− subpopulation of ovarian cancer stem cells. The present invention also provides methods to screen a subject with ovarian cancer to identify if they have an ovarian cancer comprising CD44+/CD24+/EpCam+/ECad− ovarian cancer stem cells, and methods to identify and enrich or isolate for such ovarian cancer cell populations.

    摘要翻译： 本发明一般涉及与化学治疗剂选择或富集并被MIS（Mullerian Inhibiting Substance）和MIS模拟物抑制的卵巢癌干细胞亚群相关的方法，测定，组合物和试剂盒。 特别地，本发明涉及卵巢癌干细胞的CD44 + / CD24 + / EpCam + / ECad亚群的群体。 本发明还提供了筛选具有卵巢癌的受试者以鉴定其是否具有包含CD44 + / CD24 + / EpCam + / ECad-卵巢癌干细胞的卵巢癌的方法以及用于鉴定和丰富或分离这些卵巢癌细胞群体的方法。

    Mullerian inhibiting substance levels and ovarian response
    7.
    发明授权
    Mullerian inhibiting substance levels and ovarian response 有权

    公开(公告)号：US07241577B2

    公开(公告)日：2007-07-10

    申请号：US10225503

    申请日：2002-08-20

    申请人： David B. Seifer ,  David T. MacLaughlin

    发明人： David B. Seifer ,  David T. MacLaughlin

    IPC分类号： G01N33/53 ,  C07K14/00

    CPC分类号： A61K38/22 ,  G01N33/689 ,  G01N2800/36 ,  G01N2800/367 ,  G01N2800/52

    摘要： Methods and kits are provided for assessing the ovarian reserve and predicting the ovarian response to fertility treatments in a female subject. The serum levels of MIS are shown to be positively correlated with the production and retrieval of mature oocytes and serve as prognostic indicators for the female response to fertility treatment. The MIS levels can be monitored prior to and during fertility treatment and are useful to adjust the timing and dosage of treatments in order to produce optimal outcome in individual patients, to avoid ovarian hyperstimulation, or to indicate cancellation of an unsuccessful treatment. MIS can also be administered to women to stimulate follicle development and to prevent depletion of ovarian reserve.

    Mullerian inhibiting substance levels and ovarian response
    8.
    发明授权
    Mullerian inhibiting substance levels and ovarian response 有权
    穆勒抑制物质水平和卵巢反应

    公开(公告)号：US07427486B2

    公开(公告)日：2008-09-23

    申请号：US11824154

    申请日：2007-06-29

    申请人： David B. Seifer ,  David T. MacLaughlin

    发明人： David B. Seifer ,  David T. MacLaughlin

    IPC分类号： G01N33/00 ,  G01N33/53 ,  C07K14/00

    CPC分类号： A61K38/22 ,  G01N33/689 ,  G01N2800/36 ,  G01N2800/367 ,  G01N2800/52

    摘要： Methods and kits are provided for assessing the ovarian reserve and predicting the ovarian response to fertility treatments in a female subject. The serum levels of MIS are shown to be positively correlated with the production and retrieval of mature oocytes and serve as prognostic indicators for the female response to fertility treatment. The MIS levels can be monitored prior to and during fertility treatment and are useful to adjust the timing and dosage of treatments in order to produce optimal outcome in individual patients, to avoid ovarian hyperstimulation, or to indicate cancellation of an unsuccessful treatment. MIS can also be administered to women to stimulate follicle development and to prevent depletion of ovarian reserve.

    摘要翻译： 提供方法和试剂盒用于评估卵巢储备和预测卵巢对女性受试者的生育治疗反应。 MIS的血清水平显示与成熟卵母细胞的产生和恢复正相关，并且作为女性对生育治疗反应的预后指标。 可以在生殖治疗之前和期间监测MIS水平，并且有助于调整治疗的时间和剂量，以便在个体患者中产生最佳结果，以避免卵巢过度刺激，或指示取消不成功的治疗。 也可以向妇女施用管理信息系统以刺激卵泡发育并防止卵巢储备的消耗。