中文摘要：本发明公开了一种表达载体的传递系统，该载体可以编码一种抗原，该抗原可以时空控制抗原引起的过量的免疫反应。部分表达载体传递系统包含一个与前药中佐剂相连的多聚体，因而可以形成多聚体纳米颗粒，从而在生理条件下进入细胞（如免疫细胞）。还有部分表达载体系统中，佐剂通过酶解不稳定键与多聚体集合，分裂后可以促进佐剂刺激产生免疫反应。
外文摘要：Embodiments of a system for delivering an expression vector encoding an antigen to a subject that allows for spatiotemporal control over stimulation of the subject's immune response to the antigen are provided. In some embodiments, the expression vector delivery system includes a polymer linked to an adjuvant in prodrug form that can form polymer nanoparticles and enter a cell (such as an immune cell) under physiological conditions. In some embodiments, the adjuvant is linked to the polymer by an enzyme degradable labile bond, the cleavage of which activates the adjuvant to stimulate an immune response.
NOVELTY - Inducing an immune response to an antigen in a subject, comprises administering locally to a target location in the subject, a therapeutic amount of an immunogenic composition comprising a polymer linked to an adjuvant prodrug and an expression vector comprising a nucleic acid molecule encoding the antigen; or compound having toll-like receptor (TLR) agonist activity. The polymer linked to the adjuvant prodrug and the expression vector form polymer nanoparticles in the immunogenic composition. The polymer nanoparticles can enter cells under physiological conditions.
USE - The method, compound, or immunogenic composition is useful for inducing immune response to antigen in subject, where the immune response treats tumor in the subject (all claimed).
ADVANTAGE - The adjuvants can enhance an immune response only after adequate antigen expression from the vector has occurred.
主权项：Inducing an immune response to an antigen in a subject, comprises administering locally to a target location in the subject, a therapeutic amount of an immunogenic composition comprising a polymer linked to an adjuvant prodrug and an expression vector comprising a nucleic acid molecule encoding the antigen; or compound having toll-like receptor (TLR) agonist activity. The polymer linked to the adjuvant prodrug and the expression vector form polymer nanoparticles in the immunogenic composition. The polymer nanoparticles can enter cells under physiological conditions. The adjuvant prodrug comprises an enzyme-degradable labile bond, where cleavage of the enzyme-degradable labile bond by an intracellular enzyme activates the adjuvant prodrug to induce the immune response to the antigen in the subject.
INDEPENDENT CLAIMS are:
(1) a compound, or its pharmaceutical salt, comprising a polymer linked to an adjuvant prodrug, where the polymer linked to the adjuvant prodrug forms polymer nanoparticles that enter immune cells under physiological conditions, and the adjuvant prodrug comprises an enzyme-degradable labile bond; or a compound, or a pharmaceutically acceptable salt, comprising any of formulae 13 or 16-28; and
(2) an immunogenic composition comprising the compound or pharmaceutical salt; and an expression vector comprising a nucleic acid molecule operably linked to a promoter, where the nucleic acid molecule encodes an antigen of interest.
申请号：WO2016US51037
公开/公告号：WO2017044803A1
申请日：2016-09-09
公开/公告日：2017-03-26
申请/专利权人：THE US SECRETARY DEPT OF HEALTH AND HUMAN SERVICE ; THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIV OF OXFORD
发明/设计人：SEDER ROBERT; LYNN GEOFFREY; SEYMOUR LEONARD
分类号：A61K39/39; A61K2039/53; A61K2039/55511; A61K2039/55555; A61K2039/6093
主分类号：A61K39/39
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