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1.发明授权Methods and compositions for enhancing cellular response to TGF-.beta. ligands 失效增强TGF-β配体细胞反应的方法和组合物
公开(公告)号：US5912224A
公开(公告)日：1999-06-15
申请号：US803899
申请日：1997-02-21
申请人： Patricia K. Donahoe , Tongwen Wang
发明人： Patricia K. Donahoe , Tongwen Wang
CPC分类号： C07K14/71 , A61K31/436 , A61K38/1841 , A61K38/1875 , A61K38/22 , C07K14/4702 , G01N33/6872 , A61K38/00
摘要： The present invention concerns the TGF-.beta. receptor-mediated signaling pathway. The invention is based on the unexpected finding that TGF-.beta. receptor-mediated signaling is inhibited by the cytoplasmic interactor FKBP12. The invention further concerns methods and pharmaceutical compositions for enhancing cellular response to TGF-.beta. ligands. A screening assay is also provided for identifying macrolide potentiators capable of binding FKBP12 and thereby blocking FKBP12-inhibition of TGF-.beta. receptor-mediated signaling.
摘要翻译： 本发明涉及TGF-β受体介导的信号通路。 本发明基于意想不到的发现，TGF-β受体介导的信号被细胞质相互作用者FKBP12抑制。 本发明还涉及用于增强细胞对TGF-β配体的反应的方法和药物组合物。 还提供了筛选测定法，用于鉴定能够结合FKBP12的大环内酯增效剂，从而阻断TGF-β受体介导的信号传导的FKBP12抑制。
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公开(公告)号：US5010055A
公开(公告)日：1991-04-23
申请号：US205239
申请日：1988-04-25
申请人： Patricia K. Donahoe
发明人： Patricia K. Donahoe
CPC分类号： A61K38/22 , A61K38/1808 , C07K16/26
摘要： The invention discloses a novel use of Mullerian Inhibiting Substance (MIS) as a contraceptive agent. MIS has been found to reversably inhibit the maturation of oocytes in vitro. Additionally, the invention provides a means for restoring the fertility of females who are infertile due to abnormal production of MIS.
摘要翻译： PCT No.PCT / US87 / 01514 Sec。 371日期：1988年4月25日 102（e）日期1988年4月25日PCT Filted 1987年6月24日PCT公布。 第WO88 / 00054号公报 日期1988年1月14日。本发明公开了一种Mullerian抑制物质（MIS）作为避孕药的新用途。 已经发现MIS体外可逆地抑制卵母细胞的成熟。 此外，本发明提供了一种恢复由于MIS的异常产生而不育的女性的生育能力的手段。
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公开(公告)号：US4792601A
公开(公告)日：1988-12-20
申请号：US656482
申请日：1984-10-01
IPC分类号： C07K16/00 , C07K16/18 , C12N5/16 , G01N33/53 , A61K39/395 , C12N5/00 , C12N15/00 , C12P21/00
摘要： In a method for preparing a monoclonal hybridoma which secretes antibodies against an immunogenic material, comprising sensitizing an appropriate source with an immunizing amount of a preparation of the immunogenic material, obtaining from the source lymphocytes having immune activity against the immunogenic material, and fusing the lymphocytes with an appropriate cell line to thereby form mixed hybridomas, the improvement wherein: the immunogenic material is present in the immunizing preparation in an amount not larger than 10% by weight, and wherein, after formation of the mixed hydridomas but prior to cloning, the method comprises the steps of: raising ascites fluid with the mixed hydridomas, then detecting immune specificity against the immunogenic material in the ascites raised fluid; and thereafter cloning the ascites raised cells which show immune specificity against the material.
摘要翻译： 在制备分泌针对免疫原性物质的抗体的单克隆杂交瘤的方法中，包括用免疫量的免疫原性物质的制剂对适当的来源进行敏化，从源获得具有针对免疫原性物质的免疫活性的淋巴细胞，并融合淋巴细胞 用合适的细胞系形成混合的杂交瘤，其改进在于：免疫原性物质以不大于10重量％的量存在于免疫制剂中，并且其中，在形成混合的hydridomas之后但是在克隆之前， 方法包括以下步骤：用混合的hydridomas提升腹水，然后检测腹水引起的流体中对免疫原性物质的免疫特异性; 然后克隆显示对材料的免疫特异性的腹水升高的细胞。
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公开(公告)号：US4487833A
公开(公告)日：1984-12-11
申请号：US353089
申请日：1982-03-01
摘要： In a method for preparing a monoclonal hybridoma which secretes antibodies against an immunogenic material, comprising sensitizing an appropriate source with an immunizing amount of a preparation of the immunogenic material, obtaining from the source lymphocytes having immune activity against the immunogenic material, and fusing the lymphocytes with an appropriate cell line to thereby form mixed hybridomas, the improvement wherein: the immunogenic material is present in the immunizing preparation in an amount not larger than 5% by weight, and wherein, after formation of the mixed hybridomas but prior to cloning, the method comprises the steps of: raising ascites fluid with the mixed hybridomas, then detecting immune specificity against the immunogenic material in the ascites raised fluid; and thereafter cloning the ascites raised cells which show immune specificity against the material.
摘要翻译： 在制备分泌针对免疫原性物质的抗体的单克隆杂交瘤的方法中，包括用免疫量的免疫原性物质的制剂对适当的来源进行敏化，从源获得具有针对免疫原性物质的免疫活性的淋巴细胞，并融合淋巴细胞 用适当的细胞系形成混合的杂交瘤，其改进在于：免疫原性物质以不超过5％的量存在于免疫制剂中，并且其中，在形成混合杂交瘤之后但是在克隆之前， 方法包括以下步骤：用混合杂交瘤提升腹水，然后检测腹水引起的流体中对免疫原性物质的免疫特异性; 然后克隆显示对材料的免疫特异性的腹水升高的细胞。
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5.发明申请PYRAZOLOANTHRONE AND DERIVATIVES THEREOF FOR TREATMENT OF CANCER AND EXCESS ANDROGEN STATES 有权用于治疗癌症和过敏原状态的吡咯烷酮及其衍生物公开(公告)号：US20120141605A1
公开(公告)日：2012-06-07
申请号：US13328387
申请日：2011-12-16
申请人： Jose Teixeira , Patricia K. Donahoe
发明人： Jose Teixeira , Patricia K. Donahoe
IPC分类号： A61K31/416 , A61P35/00 , A61K38/22 , A61K33/24 , A61K31/704 , A61K31/436
CPC分类号： A61K31/416 , A61K38/22 , C12Q1/6886
摘要： Provided herein are pyrazoloanthrones or functional derivatives or analogues thereof to activate MIS receptor-mediated downstream effects in a cell. In particular, methods are provided to prevent and treat cancer that expresses MIS receptor type II (MISRII) by administering to a subject at least one pyrazoloanthrone or a functional derivative or analogue thereof. Also provided herein are methods to lower plasma androgen levels in a subject, and/or for the treatment of a subject with a disease characterized by excess androgen, whereby the subject is administered at least one pyrazoloanthrone or a functional derivative or analogue thereof. Also provided are methods to decrease the dose of a chemotherapeutic agent by administering the chemotherapeutic agent with a pyrazoloanthrone or a functional derivative or analogue thereof that lowers the effective dose of the chemotherapeutic agent.
摘要翻译： 本文提供吡唑并二酮或其功能衍生物或类似物，以激活细胞中MIS受体介导的下游作用。 特别地，提供了通过向受试者施用至少一种吡唑蓝酮或其功能衍生物或类似物来预防和治疗表达MIS受体II型（MISRII）的癌症的方法。 本文还提供了降低受试者血浆雄激素水平和/或治疗具有以过量雄激素为特征的疾病的受试者的方法，由此给予受试者至少一种吡唑蓝酮或其功能性衍生物或类似物。 还提供了通过使化学治疗剂与降低化疗剂的有效剂量的吡唑蓝酮或其功能衍生物或类似物来降低化学治疗剂的剂量的方法。
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公开(公告)号：US07078032B2
公开(公告)日：2006-07-18
申请号：US10690077
申请日：2003-10-21
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。
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公开(公告)号：US06692738B2
公开(公告)日：2004-02-17
申请号：US09770339
申请日：2001-01-26
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.
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8.发明授权Use of mullerian inhibiting substance and its agonists and antagonists in the treatment of respiratory distress syndrome 失效使用穆勒抑制物质及其激动剂和拮抗剂治疗呼吸窘迫综合征
公开(公告)号：US5198420A
公开(公告)日：1993-03-30
申请号：US913789
申请日：1992-06-30
IPC分类号： A61K38/00 , A61K38/18 , C07K14/575 , C07K16/26
CPC分类号： A61K38/1808 , C07K14/575 , C07K16/26
摘要： The use of agonists or antagonists of Mullerian Inhibiting Substance to suppress or treat respiratory distress syndrom. The treatment can be accomplished by providing an effective amount of the agonist or antagonist to a neonatal or prenatal individual.
摘要翻译： 使用Mullerian抑制物质的激动剂或拮抗剂来抑制或治疗呼吸窘迫综合征。 治疗可以通过向新生儿或产前个体提供有效量的激动剂或拮抗剂来实现。
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公开(公告)号：US4404188A
公开(公告)日：1983-09-13
申请号：US287943
申请日：1981-07-29
CPC分类号： A61K38/22 , B01D15/362 , B01D15/363 , B01D15/1871 , Y10S530/85
摘要： A process for purifying Mullerian Inhibiting Substance (MIS) from testicular tissue which comprises incubating testicular tissue in a culture media in the presence of a protease inhibitor in order to extract MIS from the tissue, chromatographing the extract on an anionic exchange resin followed by chromatographing the biologically active product obtained therefrom on a cationic exchange resin; the biologically active material from the cationic exchange resin is chromatographed by lectin affinity chromatography on wheat germ lectin and then either chromatographed by lectin affinity chromatography on concanavalin A or by triazinyl dye affinity chromatography on an appropriate triazinyl dye; MIS is obtained in 8,000-fold and 15,000-fold purification over original testicular tissue.
摘要翻译： 一种从睾丸组织中纯化Mullerian抑制物质（MIS）的方法，包括在蛋白酶抑制剂存在下在培养基中孵育睾丸组织以从组织中提取MIS，在阴离子交换树脂上色谱分离提取物，随后色谱分离 由阳离子交换树脂得到的生物活性产物; 阳离子交换树脂的生物活性物质通过凝集素亲和层析对小麦胚芽凝集素进行色谱分离，然后通过凝血素亲和层析对刀豆蛋白A进行色谱分离，或通过三嗪基染料亲和色谱法在合适的三嗪基染料上进行色谱分离; 在原始睾丸组织中获得了8000倍和15000倍的纯化的MIS。
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10.发明申请公开(公告)号：US20100273160A1
公开(公告)日：2010-10-28
申请号：US12669136
申请日：2008-07-17
申请人： Patricia K. Donahoe , Paul P. Szotek , David T. MacLaughlin , Frederic Preffer , Rafael Pieretti-Vanmarcke , David Michael Dombkowski
发明人： Patricia K. Donahoe , Paul P. Szotek , David T. MacLaughlin , Frederic Preffer , Rafael Pieretti-Vanmarcke , David Michael Dombkowski
CPC分类号： A61K45/06 , A61K31/00 , A61K31/277 , A61K31/7088 , C12N5/0672 , C12N5/0695 , C12N2501/998 , C12N2503/00 , C12N2503/02 , G01N33/5011 , G01N33/5091 , G01N33/57449 , G01N2800/44 , G01N2800/54
摘要： The present invention relates to compositions and methods for treating, characterizing and diagnosing ovarian cancer. In particular, the present invention provides methods for treating and/or preventing ovarian cancer in a subject by administering to the subject an effective amount of Mullerian Inhibiting substance and/or an effective amount of an agent that inhibits BCRP1. The present invention further provides methods to identify and/or enrich for populations of ovarian cancer stem cells and populations of somatic ovarian stem cells, in particular, enrichment for populations of coelomic somatic ovarian stem cells, subcoelomic/stromal somatic ovarian stem cells and periphilar medullary somatic ovarian stem cells. The present invention also provides somatic ovarian stem cell markers and ovarian cancer stem cell markers, as well as methods to identify agents which selectively inhibit the proliferation of ovarian cancer stem cells as compared to somatic ovarian stem cells.
摘要翻译： 本发明涉及用于治疗，表征和诊断卵巢癌的组合物和方法。 特别地，本发明提供了通过向受试者施用有效量的Mullerian抑制物质和/或有效量的抑制BCRP1的药剂来治疗和/或预防受试者的卵巢癌的方法。 本发明还提供了用于鉴定和/或丰富卵巢癌干细胞和体细胞卵巢干细胞群体的方法，特别是对于体细胞性体细胞卵巢干细胞，亚骨髓/间质体细胞卵巢干细胞和腹膜髓质细胞的群体的富集 体细胞卵巢干细胞。 本发明还提供体细胞卵巢干细胞标记物和卵巢癌干细胞标记物，以及与体细胞卵巢干细胞相比选择性抑制卵巢癌干细胞增殖的试剂的方法。
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