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1. 发明申请

US20130149783A1 CLEAVABLE MODIFICATIONS TO REDUCIBLE POLY (AMIDO ETHYLENIMINES)S TO ENHANCE NUCLEOTIDE DELIVERY 审中-公开
标题翻译：可减少聚氨酯（AMIDO乙烯）的改进可以提高核子递送
公开(公告)号：US20130149783A1
公开(公告)日：2013-06-13
申请号：US13635479
申请日：2011-03-16
申请人： James William Yockman , Jonathan H. Brumbach , Sung Wan Kim
发明人： James William Yockman , Jonathan H. Brumbach , Sung Wan Kim
IPC分类号： C07C271/22
CPC分类号： C07C271/22 , A61K31/7105 , C08L71/02 , C08L2205/05 , C08L79/00
摘要： Polyplex formulations were prepared using p(TETA/CBA), its PEGylated analog, p(TETA/CBA)-g-PEG2k, and mixtures of the two species at 10/90 and 50/50 wt %, respectively. Increasing PEG wt % inhibited polyplex formation. This work demonstrates the feasibility of preparing homogenous polyplexes by altering the PEG wt % using a mixture of p(TETA/CBA) and p(TETA/CBA)-g-PEG2k products. Further, a single-step method of making p(TETA/CBA)-g-PEG2k is disclosed.
摘要翻译：使用p（TETA / CBA），其聚乙二醇化类似物，p（TETA / CBA）-g-PEG2k以及两种物质的混合物分别在10/90和50/50重量％下分别制备多功能配方。增加PEG wt％抑制聚合物形成。该工作证明了通过使用p（TETA / CBA）和p（TETA / CBA）-g-PEG2k产物的混合物改变PEG wt％来制备均匀复合物的可行性。此外，公开了制备p（TETA / CBA）-g-PEG2k的单步方法。

2. 发明授权

US07264969B1 Carrier system for specific artery wall gene delivery 有权
标题翻译：特异性动脉壁基因递送载体系统
公开(公告)号：US07264969B1
公开(公告)日：2007-09-04
申请号：US10416381
申请日：2001-11-09
申请人： Lei Yu , Sung Wan Kim , Jae-Woon Nah
发明人： Lei Yu , Sung Wan Kim , Jae-Woon Nah
IPC分类号： C12N15/88 , C12N15/00 , C12N15/87
CPC分类号： A61K48/0075
摘要： An artery wall binding peptide (AWBP) based on the artery wall cell-binding domain of apolipoprotein B-100 was conjugated to a cationic backbone configured for forming a complex with a nucleic acid to produce a composition that enhances gene transfer to artery wall cells. An illustrative cationic backbone is poly(ethylene glycol)-grafted-poly(L-lysine) (PEG-g-PLL). Methods of making and using the composition for gene transfer are also described.
摘要翻译：基于载脂蛋白B-100的动脉壁细胞结合结构域的动脉壁结合肽（AWBP）缀合到阳离子骨架上，其配置用于与核酸形成复合物，以产生增强基因转移到动脉壁细胞的组合物。一个说明性的阳离子骨架是聚（乙二醇）移植的聚（L-赖氨酸）（PEG-g-PLL）。还描述了制备和使用用于基因转移的组合物的方法。

3. 发明授权

US06652886B2 Biodegradable cationic copolymers of poly (alkylenimine) and poly (ethylene glycol) for the delivery of bioactive agents 有权
公开(公告)号：US06652886B2
公开(公告)日：2003-11-25
申请号：US09785525
申请日：2001-02-16
申请人： Cheol Hee Ahn , Sung Wan Kim
发明人： Cheol Hee Ahn , Sung Wan Kim
IPC分类号： A61K950
CPC分类号： A61K9/5146 , A61K47/59 , A61K47/593 , A61K47/595 , A61K47/60 , Y10S977/773 , Y10S977/906
摘要： A biodegradable, novel cationic coopolymer comprising a a poly(alkylenimine)(PAI), a hydrophilic polymer, and a biodegradable linker, wherein the biodegradable linker covalently links the PAI and the hydrophilic polymer. The biodegradable cationic copolymers in the present invention can be used in drug delivery and are especially useful for delivery of a nucleic acid or any anionic bioactive agent to various organs and tissues after local or systemic administration.

4. 发明授权

US06217912B1 Polyester analogue of poly-L-lysine as a soluble, biodegradable gene delivery carrier 失效
标题翻译：聚-L-赖氨酸的聚酯类似物作为可溶性，可生物降解的基因递送载体
公开(公告)号：US06217912B1
公开(公告)日：2001-04-17
申请号：US09352473
申请日：1999-07-13
申请人： Jong Sang Park , Young Hun Choi , Sung Wan Kim
发明人： Jong Sang Park , Young Hun Choi , Sung Wan Kim
IPC分类号： A61K4714
CPC分类号： C12N15/87 , A61K9/1647 , A61K47/62 , A61K48/00 , C08G63/664 , C08G63/6852
摘要： Poly[&agr;-(4-aminobutyl)-L-glycolic acid] (PAGA) is disclosed as a biodegradable composition suitable for delivering a gene into a cell. Methods of making and using PAGA are also disclosed.
摘要翻译：公开了聚[α-（4-氨基丁基）-L-乙醇酸]（PAGA）作为适于将基因输送到细胞中的可生物降解的组合物。还公开了制造和使用PAGA的方法。

5. 发明授权

US08829109B2 Cleavable modifications to reducible poly(amido ethylenimine)s to enhance nucleotide delivery 有权
标题翻译：可还原的聚（酰氨基亚乙基亚胺）的可修饰修饰以增强核苷酸的传递
公开(公告)号：US08829109B2
公开(公告)日：2014-09-09
申请号：US12266980
申请日：2008-11-07
申请人： James W. Yockman , Jonathan Brumbach , Lane V. Christensen , Sung Wan Kim
发明人： James W. Yockman , Jonathan Brumbach , Lane V. Christensen , Sung Wan Kim
IPC分类号： A61K47/48 , C08G63/48 , C08G63/91 , C08L89/00 , C12N15/00 , C08G65/334 , C08G73/02 , C08G65/333 , C08G65/332
CPC分类号： C08G65/3322 , C08G65/33306 , C08G65/33324 , C08G65/3342 , C08G65/3346 , C08G65/3348 , C08G73/0253 , C08G73/028 , C08L2205/05
摘要： Improved poly(amido ethylenimine) copolymers for gene delivery are disclosed. One illustrative embodiment includes polyethylene glycol (PEG) covalently bonded to a branched poly(triethyenetetramine/cystamine bisacrylamide) copolymer (poly(TETA/CBA)). The polyethylene glycol can be linear or branched. Another illustrative embodiment includes an RGD peptide covalently bonded to the poly(TETA/CBA)-PEG conjugate. Still another illustrative embodiment includes a method of using these compositions for transfecting a cell with a nucleic acid.
摘要翻译：公开了用于基因递送的改进的聚（酰胺乙烯亚胺）共聚物。一个说明性实施方案包括共价键合到支链聚（三亚乙基四胺/胱胺胺双丙烯酰胺）共聚物（聚（TETA / CBA））的聚乙二醇（PEG）。聚乙二醇可以是直链或支链的。另一个说明性实施方案包括与聚（TETA / CBA）-PEG缀合物共价结合的RGD肽。另一个说明性实施方案包括使用这些组合物用核酸转染细胞的方法。

6. 发明授权

US07638322B2 Hypoxia inducible VEGF plasmid for ischemic disease 失效
标题翻译：缺氧诱导型VEGF质粒缺血性疾病
公开(公告)号：US07638322B2
公开(公告)日：2009-12-29
申请号：US10546115
申请日：2004-02-23
申请人： Minhyung Lee , Sung Wan Kim
发明人： Minhyung Lee , Sung Wan Kim
IPC分类号： C12N15/00
CPC分类号： C07K14/52 , A61K48/0058 , C12N15/85 , C12N2830/002
摘要： Plasmids useful for treating ischemic disease, such as ischemic heart disease, are described. The plasmids express vascular endothelial growth factor (VEGF) under the control of a promoter (RTP801) that is up-regulated under hypoxic conditions. Pharmaceutical compositions for treating ischemic disease include mixtures of the hypoxia-regulated VEGF plasmids and pharmaceutically acceptable carriers. Methods for treating ischemic disease include administering such pharmaceutical compositions to a person in need of such treatment.
摘要翻译：描述了可用于治疗缺血性疾病如缺血性心脏病的质粒。质粒表达在缺氧条件下上调的启动子（RTP801）控制下的血管内皮生长因子（VEGF）。用于治疗缺血性疾病的药物组合物包括缺氧调节的VEGF质粒和药学上可接受的载体的混合物。治疗缺血性疾病的方法包括将这种药物组合物给予需要这种治疗的人。

7. 发明授权

US07183263B2 Linear polyethylenimine-sterol conjugates for gene delivery 有权
公开(公告)号：US07183263B2
公开(公告)日：2007-02-27
申请号：US10623020
申请日：2003-07-17
申请人： Darin Y. Furgeson , Sung Wan Kim
发明人： Darin Y. Furgeson , Sung Wan Kim
IPC分类号： A61K31/7052 , A61K31/56 , C07J9/00
CPC分类号： C07J9/00 , A61K47/59 , A61K48/0041
摘要： Linear polyethylenimine was modified with sterols, such as cholesterol, in three different geometries: linear shaped (L), T-shaped (T), and a combined linear- and T-shaped (LT), to result in linear polyethylenimine-sterol conjugates. These conjugates were mixed with nucleic acids to form complexes for delivery of the nucleic acids into cells. Mammalian cells transfected with these complexes showed protein expression levels higher than linear polyethylenimine alone, and twice that of branched polyethylenimine, but without any significant loss in cell viability. Methods of making these compositions and methods of using them for gene delivery are also described.

8. 发明授权

US08153154B2 Arginine-conjugated bioreducible poly(disulfide amine) polymers for gene delivery systems 有权
标题翻译：用于基因递送系统的精氨酸缀合的生物还原性聚（二硫化物胺）聚合物
公开(公告)号：US08153154B2
公开(公告)日：2012-04-10
申请号：US12370515
申请日：2009-02-12
申请人： Sung Wan Kim , Tae-il Kim
发明人： Sung Wan Kim , Tae-il Kim
IPC分类号： A61K9/14 , C07H21/04
CPC分类号： A61K48/0041 , A61K9/5146 , A61K47/34 , A61K47/6455 , C12N15/111 , C12N2320/32
摘要： An arginine-grafted bioreducible poly(disulfide amine) (“ABP”) as a reagent for efficient and nontoxic gene delivery is described. ABP forms positively charged nano-particles of less than 200 nm with plasmid DNA. ABP is biodegraded under reducing conditions, such as the cytoplasm. ABP exhibits much higher transfection efficiency than polyethyleneimine in mammalian cells and exhibits no cytotoxicity.
摘要翻译：描述了精氨酸接枝的可生物还原的聚（二硫化胺）（“ABP”）作为有效和无毒的基因递送的试剂。 ABP与质粒DNA形成小于200nm的带正电荷的纳米颗粒。 ABP在还原条件下生物降解，如细胞质。与哺乳动物细胞中的聚乙烯亚胺相比，ABP的转染效率高得多，不显示细胞毒性。

9. 发明授权

US07998941B2 Hypoxia inducible VEGF plasmid for ischemic disease 有权
标题翻译：缺氧诱导型VEGF质粒缺血性疾病
公开(公告)号：US07998941B2
公开(公告)日：2011-08-16
申请号：US12649141
申请日：2009-12-29
申请人： Minhyung Lee , Sung Wan Kim
发明人： Minhyung Lee , Sung Wan Kim
IPC分类号： A01N43/04 , A61K31/70
CPC分类号： C07K14/52 , A61K48/0058 , C12N15/85 , C12N2830/002
摘要： Plasmids useful for treating ischemic disease, such as ischemic heart disease, are described. The plasmids express vascular endothelial growth factor (VEGF) under the control of a promoter (RTP801) that is up-regulated under hypoxic conditions. Pharmaceutical compositions for treating ischemic disease include mixtures of the hypoxia-regulated VEGF plasmids and pharmaceutically acceptable carriers. Methods for treating ischemic disease include administering such pharmaceutical compositions to a person in need of such treatment.
摘要翻译：描述了可用于治疗缺血性疾病如缺血性心脏病的质粒。质粒在缺氧条件下上调的启动子（RTP801）的控制下表达血管内皮生长因子（VEGF）。用于治疗缺血性疾病的药物组合物包括缺氧调节的VEGF质粒和药学上可接受的载体的混合物。用于治疗缺血性疾病的方法包括将这种药物组合物给予需要这种治疗的人。

10. 发明授权

US07863470B2 Linear polyethylenimine-sterol conjugates for gene delivery 有权
标题翻译：用于基因递送的线性聚乙烯亚胺 - 甾醇缀合物
公开(公告)号：US07863470B2
公开(公告)日：2011-01-04
申请号：US11711933
申请日：2007-02-27
申请人： Darin Y. Furgeson , Sung Wan Kim
发明人： Darin Y. Furgeson , Sung Wan Kim
IPC分类号： C07J9/00
CPC分类号： C07J9/00 , A61K47/59 , A61K48/0041
摘要： Linear polyethylenimine was modified with sterols, such as cholesterol, in three different geometries: linear shaped (L), T-shaped (T), and a combined linear- and T-shaped (LT), to result in linear polyethylenimine-sterol conjugates. These conjugates were mixed with nucleic acids to form complexes for delivery of the nucleic acids into cells. Mammalian cells transfected with these complexes showed protein expression levels higher than linear polyethylenimine alone, and twice that of branched polyethylenimine, but without any significant loss in cell viability. Methods of making these compositions and methods of using them for gene delivery are also described.
摘要翻译：线性聚乙烯亚胺用甾醇如胆固醇在三种不同的几何形状中进行了改性：线形（L），T形（T）和组合的线形和T形（LT），得到线性聚乙烯亚胺 - 固醇共轭物。将这些缀合物与核酸混合以形成用于将核酸递送到细胞中的复合物。用这些复合物转染的哺乳动物细胞显示蛋白质表达水平高于单独的线性聚乙烯亚胺，是支链聚乙烯亚胺的两倍，但细胞活力没有任何显着的损失。还描述了制备这些组合物的方法和使用它们进行基因递送的方法。

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