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2. 发明申请

US20040063912A1 Central airway administration for systemic delivery of therapeutics 审中-公开
标题翻译：中枢气道管理系统性递送治疗
公开(公告)号：US20040063912A1
公开(公告)日：2004-04-01
申请号：US10622108
申请日：2003-07-17
申请人： The Brigham and Women's Hospital, Inc. , Children's Medical Center Corporation , Brandeis University , Syntonix Pharmaceuticals, Inc.
发明人： Richard S. Blumberg , Wayne I. Lencer , Neil E. Simister , Alan J. Bitonti
IPC分类号： C07K014/54 , C07K016/46
CPC分类号： A61K9/0073 , A61K9/0078 , C07K19/00 , C07K2319/00
摘要： The present invention relates to methods and products for the transepithelial systemic delivery of therapeutics. In particular, the invention relates to methods and compositions for the systemic delivery of therapeutics by administering an aerosol containing antibodies or conjugates of a therapeutic agent with an FcRn binding partner to epithelium of central airways of the lung. The methods and products are adaptable to a wide range of therapeutic agents, including proteins and polypeptides, nucleic acids, drugs, and others. In particular embodiments the conjugates are fusion proteins in which a therapeutic polypeptide is joined at its C terminal end through a peptide linker to the N terminal end of an immunoglobulin Fc gamma heavy chain, wherein the linker includes Glycine and Serine residues and is preferably 15 amino acids long. In one embodiment the fusion protein includes an interferon-alpha 2b (IFN-null2b) joined at its C terminal end through a peptide linker having a sequence Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly-Ser (SEQ ID NO:29) to the N terminal end of a human Fcnull1 heavy chain. The methods and products have the advantage of not requiring administration to the deep lung in order to effect systemic delivery.
摘要翻译：本发明涉及用于治疗的跨上皮系统递送的方法和产品。特别地，本发明涉及通过将含有治疗剂的抗体或缀合物与FcRn结合配偶体的气溶胶施用于肺的中央气道的上皮来全身递送治疗剂的方法和组合物。方法和产品适用于广泛的治疗剂，包括蛋白质和多肽，核酸，药物等。在具体实施方案中，缀合物是融合蛋白，其中治疗性多肽在其C末端通过肽接头连接到免疫球蛋白Fcγ重链的N末端，其中所述连接体包括甘氨酸和丝氨酸残基，并且优选为15个氨基酸长。在一个实施方案中，融合蛋白包括其C末端通过具有序列Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly-Ser-Gly-Gly-Gly-Gly-Ser- Gly-Gly-Gly-Gly-Ser（SEQ ID NO：29）至人Fcγm1重链的N末端。所述方法和产品具有不需要施用于深肺以实现系统递送的优点。

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