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公开(公告)号：US07235625B2
公开(公告)日：2007-06-26
申请号：US11139730
申请日：2005-05-26
CPC分类号： C07K14/685 , A61K31/519 , A61K33/24 , A61K38/12 , A61K45/06 , Y10S436/811 , A61K2300/00
摘要： Multiple agent therapy for treatment of sexual dysfunction, including male erectile dysfunction, with sequential administration a type V phosphodiesterase inhibitor (PDE-5), such as sildenafil, preferably wherein the PDE-5 inhibitor is administered by oral dose means, and a melanocortin 3 and/or 4 receptor agonist, such as Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH (PT-141) preferably wherein the PT-141 is formulated for and administered by intranasal means, and further preferably wherein the PDE-5 inhibitor is administered prior to PT-141.
摘要翻译： 用于治疗性功能障碍（包括男性勃起功能障碍）的多药物治疗，连续施用V型磷酸二酯酶抑制剂（PDE-5），例如西地那非，其中PDE-5抑制剂通过口服剂量方式施用，黑皮质素3 和/或4受体激动剂，例如Ac-Nle-cyclo（-Asp-His-D-Phe-Arg-Trp-Lys）-OH（PT-141），优选其中PT-141配制用于鼻内给药 是指，进一步优选其中PDE-5抑制剂在PT-141之前施用。
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公开(公告)号：US07038107B2
公开(公告)日：2006-05-02
申请号：US10113664
申请日：2002-03-28
申请人： Cunqi Cui , Lisa E. Diamond , John S. Logan
发明人： Cunqi Cui , Lisa E. Diamond , John S. Logan
IPC分类号： A01K67/033 , A01K67/027 , C12N15/00
CPC分类号： C07K14/005 , A01K67/027 , A01K2227/108 , A01K2267/02 , C12N2740/10022 , C12Q1/701 , C12Q1/702
摘要： Porcine nucleic acid sequences flanking potentially infectious porcine endogenous retroviral (PERV) insertion sites have been identified and isolated. The unique flanking sequences include porcine nucleic acid sequences that flank the 3′ end and porcine nucleic acid sequences that flank the 5′ end of PERV insertion sites. The present invention provides compositions and methods for detecting presence of PERV in a sample, particularly those with infectious potential. In addition, the invention relates to breeding of pigs or selection of porcine tissue that is free of infectious PERV for use as a xenotransplant tissue.
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公开(公告)号：US20080124396A1
公开(公告)日：2008-05-29
申请号：US11932737
申请日：2007-10-31
IPC分类号： A61K47/32 , A61P37/06 , A61K9/00 , A61K38/19 , A61K39/395
CPC分类号： C07K16/00 , A61K39/001 , A61K47/59 , A61K47/60 , A61K47/61 , A61K47/645 , A61K2039/6093
摘要： One aspect of the present invention relates to methods and compositions for attenuating xenograft rejection by administering, to an animal receiving the xenograft, an amount of a polymer-derivatized xenoantigen (hereinafter “xenopolymer”) effective for inhibiting or lessening the severity of hyperacute rejection response (HAR), or other immunological response to the graft, that is dependent on the presence of the xenoantigen on the grafted tissues or cells. In certain embodiments, the xenopolymer is administered in an amount sufficient to neutralize host antibodies (“xenoreactive antibodies” or “XNA”) immunoreactive with the xenoantigen. The xenopolymer may additionally, or alternatively, be used as a tolerogen (or anergen) for the xenoantigen, e.g., able to suppress, to some degree, the production/secretion of XNAs by the immune system of the host.
摘要翻译： 本发明的一个方面涉及通过向接受异种移植物的动物施用一定量的有效抑制或减轻超急性排斥反应严重性的聚合物衍生的异种抗原（以下称为“异戊烯”）来减弱异种移植排斥的方法和组合物 （HAR）或其他对移植物的免疫应答，这取决于移植组织或细胞上异种抗原的存在。 在某些实施方案中，以足以中和与异种抗原免疫反应的宿主抗体（“异反应性抗体”或“XNA”）的量施用异种聚合物。 异源聚合物可以另外地或替代地用作异种抗原的耐受原（或过敏原），例如能够在一定程度上抑制宿主的免疫系统产生/分泌XNA。
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4.发明授权Method of producing transgenic animals for xenotransplantation expressing both an enzyme masking or reducing the level of the gal epitope and a complement inhibitor 失效用于异源移植的转基因动物的生产方法，其表达掩蔽或降低gal表位水平的酶和补体抑制剂
公开(公告)号：US6166288A
公开(公告)日：2000-12-26
申请号：US675773
申请日：1996-07-03
申请人： Lisa E. Diamond , John S. Logan , Geurard W. Byrne , Ajay Sharma
发明人： Lisa E. Diamond , John S. Logan , Geurard W. Byrne , Ajay Sharma
IPC分类号： A01K67/027 , A61K38/00 , A61K38/45 , A61K48/00 , A61P37/06 , C07K14/705 , C12N5/10 , C12N9/10 , C12N15/09 , C12N15/85 , A01K67/00
CPC分类号： C12N15/8509 , A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2227/108 , A01K2267/025 , A61K38/00 , A61K48/00 , C07K14/705 , C12N9/1048
摘要： A method of xenotransplanting organs, tissues, cells or non-viable components which reduces or prevents antibody-mediated rejections, including hyperacute rejection, is provided wherein transgenic animals are produced that express at least one enzyme which masks or reduces the level of the antigenic Gal.alpha.(1,3)Gal or gal epitope, and at least one complement inhibitor such as CD59, DAF and/or MCP. The transgenic animals which express both a gal epitope-reducing enzyme and a complement inhibitor will have masked or reduced levels of the gal epitope and will be much less likely to produce an antibody-mediated rejection following transplantation, and the expression of the complement inhibitor will also suppress complement activation and reduce even further a severe immune reaction following the transplantation of donor organs, tissue, cells or non-viable components from the transgenic animals so produced. In addition, transgenic animals are provided which express a plurality of complement inhibitors or other proteins from a locus of genes at a single integration site. The present invention is thus advantageous in that it can provide xenogeneic organs, tissues, cells and non-viable components which can be transplanted safely and effectively into humans with a reduction or elimination of antibody-mediated rejection to an extent not previously possible, and which will significantly reduce the need to obtain donor organs, tissues, cells or non-viable components from human or primate donors.
摘要翻译： 提供了一种异种移植器官，组织，细胞或非可行组分的方法，其减少或预防抗体介导的排斥，包括超急性排斥反应，其中产生转基因动物，其表达至少一种掩蔽或降低抗原Gal水平的酶 α（1,3）Gal或gal表位，以及至少一种补体抑制剂如CD59，DAF和/或MCP。 表达gal表位还原酶和补体抑制剂的转基因动物将具有掩蔽或降低gal表位的水平，并且在移植后将不太可能产生抗体介导的排斥反应，并且补体抑制剂的表达将 还抑制补体激活，并在从所产生的转基因动物中移植供体器官，组织，细胞或不可行组分之后进一步减少严重的免疫反应。 此外，提供转基因动物，其在单一整合位点从基因位点表达多种补体抑制剂或其它蛋白质。 因此，本发明的优点在于其可以提供异种器官，组织，细胞和非活组分，其可以安全有效地移植到人中，其具有在先前不可能的程度减少或消除抗体介导的排斥反应，以及哪些 将显着减少从人或灵长类动物供体获得供体器官，组织，细胞或不可行组分的需要。
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公开(公告)号：US06572867B1
公开(公告)日：2003-06-03
申请号：US09292153
申请日：1999-04-15
IPC分类号： A61K4726
CPC分类号： C07K16/00 , A61K39/001 , A61K47/59 , A61K47/60 , A61K47/61 , A61K47/645 , A61K2039/6093
摘要： One aspect of the present invention relates to methods and compositions for attenuating xenograft rejection by administering, to an animal receiving the xenograft, an amount of a polymer-derivatized xenoantigen (hereinafter “xenopolymer”) effective for inhibiting or lessening the severity of hyperacute rejection response (HAR), or other immunological response to the graft, that is dependent on the presence of the xenoantigen on the grafted tissues or cells. In certain embodiments, the xenopolymer is administered in an amount sufficient to neutralize host antibodies (“xenoreactive antibodies” or “XNA”) immunoreactive with the xenoantigen. The xenopolymer may additionally, or alternatively, be used as a tolerogen (or anergen) for the xenoantigen, e.g., able to suppress, to some degree, the production/secretion of XNAs by the immune system of the host.
摘要翻译： 本发明的一个方面涉及通过向接受异种移植物的动物施用一定量的有效抑制或减轻超急性排斥反应严重性的聚合物衍生的异种抗原（以下称为“异戊烯”）来减弱异种移植排斥的方法和组合物 （HAR）或其他对移植物的免疫应答，这取决于移植组织或细胞上异种抗原的存在。 在某些实施方案中，以足以中和与异种抗原免疫反应的宿主抗体（“异反应性抗体”或“XNA”）的量施用异种聚合物。 异源聚合物可以另外地或替代地用作异种抗原的耐受原（或过敏原），例如能够在一定程度上抑制宿主的免疫系统产生/分泌XNA。
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