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    • 3. 发明申请
    • POLYAMIDES FOR NUCLEIC ACID DELIVERY
    • 用于核酸递送的聚酰胺
    • WO2005062854A2
    • 2005-07-14
    • PCT/US2004/042949
    • 2004-12-20
    • UNIVERSITY OF CINCINNATIREINEKE, Theresa, M.
    • REINEKE, Theresa, M.
    • A61K8/00C12N15/113
    • C12N15/113C12N2310/13C12N2310/51
    • The present invention describes reagents and methods for using a concatemerized double-stranded oligonucleotide molecules (CODN) for transcription factor decoys. In one embodiment, the concatemers consists of a variable number of end-to-end repeated copies of a short (more than 5, 10, 15, 20, 2, 3035, 40, 45, 50, 75, 100, or more bp but generally less than about 3 kb) dsDNA containing a sequence or sequences that act as transcription factor decoys. The present invention also provides for the use of the polymers for CODN/polymer complexes to a specific cell type; thus the agent can be made organ, tissue and/or cell-type specific. In another embodiment, the present invention provides for use of the CODN’s in vitro or in vivo , in isolated cells or intact animals in which specific blockade of transcription factors or delivery of DNA or other biological effector is desirable. In one embodiment, this includes use as a research tool, including studies of specific genes and studies to identify specific genes regulated by the transcription factors targeted. In another embodiment, the present invention provides for using polyamides for NF-kB-specific CODN delivery in the treatment of myocardial ischemia/reperfusion and myocardial infarction, heart failure and hypertrophy, cardioprotection, stroke, neuroprotection, sepsis, arthritis, asthma, heritable inflammatory disorders, cancer, heritable immune dysfunctions, inflammatory processes, whether caused by disease or injury or infection, oxidative stress to any organ whether caused by disease, surgery or injury. The decoys may be any transcription factors, including, but not limited to, NF-kB, AP-1, ATF2, ATF3, SP1 and others.
    • 本发明描述了用于转录因子诱饵的并行双链寡核苷酸分子(CODN)的试剂和方法。 在一个实施方案中,连续体由可变数量的短(多于5,10,15,20,2,30,35,40,45,50,75,100,或更多bp)的端对端重复拷贝组成 但通常小于约3kb)dsDNA,其含有作为转录因子诱饵的序列或序列。 本发明还提供了聚合物对于特定细胞类型的CODN /聚合物复合物的用途; 因此该制剂可以被制成器官,组织和/或细胞型特异性。 在另一个实施方案中,本发明提供在体外或体内在分离的细胞或完整动物中使用CODN,其中转录因子的特异性封闭或DNA或其他生物效应物的递送是期望的。 在一个实施方案中,这包括用作研究工具,包括特定基因的研究和研究以鉴定由靶向的转录因子调节的特定基因。 在另一个实施方案中,本发明提供在治疗心肌缺血/再灌注和心肌梗塞,心力衰竭和肥大,心脏保护,中风,神经保护,败血症,关节炎,哮喘,遗传性炎症中使用聚酰胺用于NF-kB特异性CODN递送 疾病,癌症,遗传性免疫功能障碍,炎症过程,无论是由疾病或损伤或感染引起,对任何器官的氧化应激,无论是由疾病,手术还是损伤引起。 诱饵可以是任何转录因子,包括但不限于NF-kB,AP-1,ATF2,ATF3,SP1等。
    • 4. 发明申请
    • POLYAMIDES AND POLYAMIDE COMPLEXES FOR DELIVERY OF OLIGONUCLEOTIDE DECOYS
    • 用于交付寡糖衍生物的聚酰胺和聚酰胺复合物
    • WO2005084180A2
    • 2005-09-15
    • PCT/US2004/042948
    • 2004-12-20
    • UNIVERSITY OF CINCINNATIREINEKE, Theresa, M.JONES, Keith, W.
    • REINEKE, Theresa, M.JONES, Keith, W.
    • A61K8/00C12N15/113
    • C12N15/113C12N2310/13C12N2310/51
    • The present invention provides a new class of non-viral transduction vectors that can be used for both in vivo and in vitro applications. In particular, these vectors can be used for gene transfer applications. These new gene transduction vectors can achieve transfer efficiencies far greater to commercially available polymeric and liposomal gene transfer vectors while maintaining little or no toxicity in vitro. Their low in vitro toxicity makes them ideal candidates for in vivo use. The present invention also provides a gene transfer vector that has comparable efficiency to a viral vector without the potential for a life-threatening immune response. Furthermore, the unique polycationic structure of these polymers associates with many suitable biologically active molecule, including oligonucleotides and polypeptides and other compounds that poses multiple cationic sites. The polymer can act as a delivery vehicle for the associated biologically active molecule, in vivo or in vitro, to the cells of interest for the biologically active molecule. Complexes according to the invention or portions thereof, can comprise a cellular delivery molecule or agent that can facilitate the translocation of the complex or portion thereof into cells. In some embodiments, cellular delivery molecules for use in the present invention may comprise one or more one or more polymers of the present invention, e.g., polyamides, dendritic macromolecules (polymers comprising an oligoamine shell and a cyclodextrin core), and carbohydrate-containing degradable polyesters.
    • 本发明提供了可用于体内和体外应用的新一类非病毒转导载体。 特别地,这些载体可用于基因转移应用。 这些新的基因转导载体可以实现远远大于商业上可获得的聚合物和脂质体基因转移载体的转移效率,同时在体外保持很少或没有毒性。 它们的低体外毒性使其成为体内使用的理想候选物。 本发明还提供了具有与病毒载体相当的效率而不具有危及生命的免疫应答潜力的基因转移载体。 此外,这些聚合物的独特的聚阳离子结构与许多合适的生物活性分子(包括寡核苷酸和多肽)以及构成多个阳离子位点的其它化合物缔合。 聚合物可以作为生物活性分子感兴趣的细胞在体内或体外作为相关生物活性分子的递送载体。 根据本发明或其部分的复合物可以包含可以促进复合物或其部分转运到细胞中的细胞递送分子或试剂。 在一些实施方案中,用于本发明的细胞递送分子可以包含本发明的一种或多种一种或多种聚合物,例如聚酰胺,树突状大分子(包含寡胺壳和环糊精核心的聚合物)和含碳水化合物的可降解 聚酯。
    • 5. 发明申请
    • THERANOSTIC POLYCATION BEACONS COMPRISING OLIGOETHYLENEAMINE REPEATING UNITS AND LANTHANIDE CHELATES
    • 含有低聚乙烯胺重复单元和镧系螯合剂的舒张性聚阳离子通道
    • WO2011006011A3
    • 2011-04-28
    • PCT/US2010041432
    • 2010-07-08
    • VIRGINIA TECH INTELL PROPREINEKE THERESABRYSON JOSHUA
    • REINEKE THERESABRYSON JOSHUA
    • C08G69/44C08G73/16C12Q1/68G01N24/08G01N33/68
    • C12N15/87A61K49/0019A61K49/0054A61K49/12C07C237/10C08G69/26C12Q1/6816C12Q2525/301C12Q2565/601
    • The present invention relates to vehicles for delivering macromolecules into cells. More particularly, embodiments of the invention relate to compounds and methods for binding and compacting nucleic acids into nanoparticles for transferring the polynucleotides into cells and which can be configured to provide a mechanism for visualization of the delivery vehicles on the nm/µm scale by microscopy and on the sub-mm scale by magnetic resonance imaging. Polycations according to embodiments of the invention have been designed to contain repeated oligoethyleneamines, for binding and compacting nucleic acids into nanoparticles, and lanthanide (Ln) chelates (for example, using luminescent europium Eu3+ and paramagnetic gadolinium Gd3+). Especially preferred, are structures chelated with either Eu3+ or Gd3+ for microscopy or MRI imaging, respectively. Such chelated lanthanides allow the visualization of the delivery vehicle both on the nm/µm scale by way of microscopy and on the sub-mm scale using MRI.
    • 本发明涉及用于将大分子递送到细胞中的载体。 更具体地说,本发明的实施方案涉及用于将核酸结合和压缩成纳米颗粒以将多核苷酸转移入细胞中的化合物和方法,并且其可以被配置成通过显微镜提供用于以nm /μm尺度显示递送载体的机制,和 通过磁共振成像在亚毫米级。 根据本发明的实施方案的聚阳离子已被设计成含有重复的寡聚乙烯胺,用于将核酸结合和压缩成纳米颗粒,以及镧系元素(Ln)螯合物(例如,使用发光铕Eu3 +和顺磁性钆Gd3 +)。 特别优选的是分别与Eu3 +或Gd3 +螯合的用于显微镜或MRI成像的结构。 这种螯合的镧系元素允许通过显微镜以nm /μm尺度显示递送载体并且使用MRI以亚毫米尺度显示递送载体。