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1.发明申请公开(公告)号：US20090202511A1
公开(公告)日：2009-08-13
申请号：US11631248
申请日：2005-07-01
CPC分类号： C12N15/62 , A61K38/00 , A61K38/465 , A61K47/6849 , C07K16/2821 , C07K2317/77 , C07K2319/035 , C12N9/16 , C12Y301/04012 , Y10T428/2982 , Y10T428/2991
摘要： The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use 10 of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.
摘要翻译： 本发明涉及用于递送溶酶体蛋白质的组合物和方法。 本文描述的组合物和方法允许将外源性溶酶体蛋白靶向递送至细胞表面蛋白质，从而允许其通过非网格蛋白途径内化。 本发明还涉及用于溶酶体贮积病的酶替代疗法的组合物和方法的用途10。 还提供了可用于制备和使用本发明组合物的核酸，重组细胞和试剂盒。
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2.发明授权公开(公告)号：US08889127B2
公开(公告)日：2014-11-18
申请号：US11631248
申请日：2005-07-01
IPC分类号： A61K38/46 , A61K39/00 , B32B5/16 , C12N9/96 , C12N9/14 , C07H21/04 , A61K47/48 , C12N9/16 , A61K38/00
CPC分类号： C12N15/62 , A61K38/00 , A61K38/465 , A61K47/6849 , C07K16/2821 , C07K2317/77 , C07K2319/035 , C12N9/16 , C12Y301/04012 , Y10T428/2982 , Y10T428/2991
摘要： The present invention relates to compositions and methods for delivering lysosomal proteins. The compositions and methods described herein permit the targeted delivery of exogenous lysosomal proteins to cell surface proteins that allow their internalization via non-clathrin pathways. The present invention further relates to the use of the compositions and methods for enzyme replacement therapy of lysosomal storage diseases. Nucleic acids, recombinant cells and kits useful for making and using the compositions of the invention are also provided.
摘要翻译： 本发明涉及用于递送溶酶体蛋白质的组合物和方法。 本文描述的组合物和方法允许将外源性溶酶体蛋白靶向递送至细胞表面蛋白质，从而允许其通过非网格蛋白途径内化。 本发明还涉及组合物和方法用于溶酶体贮积病的酶替代疗法的用途。 还提供了可用于制备和使用本发明组合物的核酸，重组细胞和试剂盒。
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公开(公告)号：US09707299B2
公开(公告)日：2017-07-18
申请号：US12600947
申请日：2008-05-22
CPC分类号： A61K47/549 , A61K47/605 , A61K47/6849 , A61K47/6921
摘要： The invention provides a method for delivering a cargo molecule into a cell using a targeted DNA-based carrier (e.g., DNA dendrimer). Compositions and kits useful in the practice of the methods are also provided.
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公开(公告)号：US20100151005A1
公开(公告)日：2010-06-17
申请号：US12600947
申请日：2008-05-22
IPC分类号： A61K9/127 , C12N5/071 , A61K31/7105 , A61P43/00
CPC分类号： A61K47/549 , A61K47/605 , A61K47/6849 , A61K47/6921
摘要： The invention provides a method for delivering a cargo molecule into a cell using a targeted DNA-based carrier (e.g., DNA dendrimer). Compositions and kits useful in the practice of the methods are also provided.
摘要翻译： 本发明提供了使用靶向的基于DNA的载体（例如，DNA树枝状聚合物）将货物分子递送到细胞中的方法。 还提供了在实践方法中有用的组合物和试剂盒。
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5.发明申请Method and Compositions for Polymer Nanocarriers Containing Therapeutic Molecules 有权含有治疗分子的聚合物纳米载体的方法和组合物公开(公告)号：US20100316571A1
公开(公告)日：2010-12-16
申请号：US12739584
申请日：2008-10-27
CPC分类号： A61K9/5153 , A61K9/1075 , A61K47/60
摘要： A method of controlling a physical characteristic of polymeric nanocarrier-encapsulated protein particles includes altering or selecting a weight percentage of a hydrophobic polymer block in a total amphiphilic diblock copolymer of a primary emulsion of a double emulsion, freeze-thaw technique. The primary emulsion is formed using a freeze-thaw cycle of the amphiphilic diblock copolymer and a protein having a molecular weight of up to or equal to 300,000 Da. Selection of the hydrophobic polymer block percentage alters one or more characteristics of the resulting nanoparticles, such as shape. Thus, as one aspect, a method of producing filamentous polymeric nanocarrier-encapsulated protein (i.e., active enzyme) particles involves forming a primary emulsion using a freeze-thaw cycle of (i) an amphiphilic diblock copolymer, which has a molecular weight of about 10,000 to about 100,000 Da and comprises a conjugate of the hydrophobic polymer block and a hydrophilic polymer block, wherein the amphiphilic diblock copolymer comprises greater than 81% to about 95% by weight of the hydrophobic polymer block; and a protein having a molecular weight of up to or equal to about 300,000 Da. Various compositions comprising such filamentous-shaped nanocarrier particles, and methods of use for diagnosis and therapy are disclosed.
摘要翻译： 控制聚合物纳米载体包封的蛋白质颗粒的物理特性的方法包括改变或选择双乳液的初级乳液的全两亲双嵌段共聚物中的疏水性聚合物嵌段的重量百分数，冻融技术。 使用两亲二嵌段共聚物的冻融循环和分子量为至多300,000Da的蛋白质形成初级乳液。 疏水聚合物嵌段百分比的选择改变所得纳米颗粒的一种或多种特性，例如形状。 因此，一方面，生产丝状聚合物纳米载体包封的蛋白质（即活性酶）颗粒的方法包括使用（i）两亲性二嵌段共聚物（其分子量约为）的冷冻 - 解冻循环形成初级乳液 10,000至约100,000Da，并且包含疏水性聚合物嵌段和亲水性聚合物嵌段的共轭物，其中两亲性二嵌段共聚物包含大于疏水性聚合物嵌段重量的81％至约95％ 和分子量大于或等于约300,000Da的蛋白质。 公开了包含这种丝状纳米载体颗粒的各种组合物，以及用于诊断和治疗的方法。
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6.发明申请公开(公告)号：US20090258078A1
公开(公告)日：2009-10-15
申请号：US12481876
申请日：2009-06-10
CPC分类号： A61K38/44 , A61K9/5031 , A61K9/5153 , A61K9/5192 , A61K38/48 , A61K47/34
摘要： The present invention is a method for encapsulating active protein in a polymeric nanocarrier. The instant method employs homogenization at subzero temperatures so that enzyme activity is retained. Enzymes which can be encapsulated by the present method include, for example, antioxidant enzymes and xenobiotic detoxifying enzymes. Encapsulation of an enzyme protects it from protease degradation and increases therapeutic half-life. Advantageously, polymeric nanoparticles of the invention are permeable to enzyme substrates and therefore enzymes encapsulated by the instant method can exert their effect without release from the nanocarrier. Methods for decomposing a reactive oxygen species, protecting against vascular oxidative stress, and detoxifying a xenobiotic are also provided.
摘要翻译： 本发明是将活性蛋白质包封在聚合物纳米载体中的方法。 本方法在亚零温度下使用均匀化，从而保留酶活性。 可以通过本方法包封的酶包括例如抗氧化酶和异生物解毒酶。 酶的包封可以防止蛋白酶降解并增加治疗半衰期。 有利地，本发明的聚合物纳米颗粒对酶底物是可渗透的，因此通过本发明方法包封的酶可以发挥其作用而不从纳米载体释放。 还提供了分解活性氧物质，保护血管氧化应激和解毒异种生物的方法。
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7.发明申请METHOD AND COMPOSITIONS FOR POLYMER NANOCARRIERS CONTAINING THERAPEUTIC MOLECULES 有权含有治疗分子的聚合物纳米颗粒的方法和组合物公开(公告)号：US20090110741A1
公开(公告)日：2009-04-30
申请号：US11925834
申请日：2007-10-27
CPC分类号： A61K9/5153
摘要： A method of controlling a physical characteristic of polymeric nanocarrier-encapsulated protein particles includes altering or selecting a weight percentage of a hydrophobic polymer block in a total amphiphilic diblock copolymer of a primary emulsion of a double emulsion, freeze-thaw technique. The primary emulsion is formed using a freeze-thaw cycle of the amphiphilic diblock copolymer and a protein having a molecular weight of up to or equal to 300,000 Da. Selection of the hydrophobic polymer block percentage alters one or more characteristics of the resulting nanoparticles, such as shape. Thus, as one aspect, a method of producing filamentous polymeric nanocarrier-encapsulated protein (i.e., active enzyme) particles involves forming a primary emulsion using a freeze-thaw cycle of (i) an amphiphilic diblock copolymer, which has a molecular weight of about 10,000 to about 100,000 Da and comprises a conjugate of the hydrophobic polymer block and a hydrophilic polymer block, wherein the amphiphilic diblock copolymer comprises greater than 81% to about 95% by weight of the hydrophobic polymer block; and a protein having a molecular weight of up to or equal to about 300,000 Da. Various compositions comprising such filamentous-shaped nanocarrier particles, and methods of use for diagnosis and therapy are disclosed.
摘要翻译： 控制聚合物纳米载体包封的蛋白质颗粒的物理特性的方法包括改变或选择双乳液的初级乳液的全两亲双嵌段共聚物中的疏水性聚合物嵌段的重量百分数，冻融技术。 使用两亲二嵌段共聚物的冻融循环和分子量为至多300,000Da的蛋白质形成初级乳液。 疏水聚合物嵌段百分比的选择改变所得纳米颗粒的一种或多种特性，例如形状。 因此，一方面，生产丝状聚合物纳米载体包封的蛋白质（即活性酶）颗粒的方法包括使用（i）两亲性二嵌段共聚物（其分子量约为）的冷冻 - 解冻循环形成初级乳液 10,000至约100,000Da，并且包含疏水性聚合物嵌段和亲水性聚合物嵌段的共轭物，其中两亲性二嵌段共聚物包含大于疏水性聚合物嵌段重量的81％至约95％ 和分子量大于或等于约300,000Da的蛋白质。 公开了包含这种丝状纳米载体颗粒的各种组合物，以及用于诊断和治疗的方法。
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8.发明授权Method and compositions for polymer nanocarriers containing therapeutic molecules 有权含有治疗分子的聚合物纳米载体的方法和组合物公开(公告)号：US08568786B2
公开(公告)日：2013-10-29
申请号：US12739584
申请日：2008-10-27
CPC分类号： A61K9/5153 , A61K9/1075 , A61K47/60
摘要： A method of controlling a physical characteristic of polymeric nanocarrier-encapsulated protein particles includes altering or selecting a weight percentage of a hydrophobic polymer block in a total amphiphilic diblock copolymer of a primary emulsion of a double emulsion, freeze-thaw technique. The primary emulsion is formed using a freeze-thaw cycle of the amphiphilic diblock copolymer and a protein having a molecular weight of up to or equal to 300,000 Da. Selection of the hydrophobic polymer block percentage alters one or more characteristics of the resulting nanoparticles, such as shape. Thus, as one aspect, a method of producing filamentous polymeric nanocarrier-encapsulated protein (i.e., active enzyme) particles involves forming a primary emulsion using a freeze-thaw cycle of (i) an amphiphilic diblock copolymer, which has a molecular weight of about 10,000 to about 100,000 Da and comprises a conjugate of the hydrophobic polymer block and a hydrophilic polymer block, wherein the amphiphilic diblock copolymer comprises greater than 81% to about 95% by weight of the hydrophobic polymer block; and a protein having a molecular weight of up to or equal to about 300,000 Da. Various compositions comprising such filamentous-shaped nanocarrier particles, and methods of use for diagnosis and therapy are disclosed.
摘要翻译： 控制聚合物纳米载体包封的蛋白质颗粒的物理特性的方法包括改变或选择双乳液的初级乳液的全两亲双嵌段共聚物中的疏水性聚合物嵌段的重量百分数，冻融技术。 使用两亲二嵌段共聚物的冻融循环和分子量为至多300,000Da的蛋白形成初级乳液。 疏水聚合物嵌段百分比的选择改变所得纳米颗粒的一种或多种特性，例如形状。 因此，一方面，生产丝状聚合物纳米载体包封的蛋白质（即活性酶）颗粒的方法包括使用（i）两亲性二嵌段共聚物（其分子量约为）的冷冻 - 解冻循环形成初级乳液 10,000至约100,000Da，并且包含疏水性聚合物嵌段和亲水性聚合物嵌段的共轭物，其中两亲性二嵌段共聚物包含大于疏水性聚合物嵌段重量的81％至约95％ 和分子量大于或等于约300,000Da的蛋白质。 公开了包含这种丝状纳米载体颗粒的各种组合物，以及用于诊断和治疗的方法。
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9.发明授权Method and compositions for polymer nanocarriers containing therapeutic molecules 有权含有治疗分子的聚合物纳米载体的方法和组合物公开(公告)号：US07927629B2
公开(公告)日：2011-04-19
申请号：US11925834
申请日：2007-10-27
CPC分类号： A61K9/5153
摘要： A method of controlling a physical characteristic of polymeric nanocarrier-encapsulated protein particles includes altering or selecting a weight percentage of a hydrophobic polymer block in a total amphiphilic diblock copolymer of a primary emulsion of a double emulsion, freeze-thaw technique. The primary emulsion is formed using a freeze-thaw cycle of the amphiphilic diblock copolymer and a protein having a molecular weight of up to or equal to 300,000 Da. Selection of the hydrophobic polymer block percentage alters one or more characteristics of the resulting nanoparticles, such as shape. Thus, as one aspect, a method of producing filamentous polymeric nanocarrier-encapsulated protein (i.e., active enzyme) particles involves forming a primary emulsion using a freeze-thaw cycle of (i) an amphiphilic diblock copolymer, which has a molecular weight of about 10,000 to about 100,000 Da and comprises a conjugate of the hydrophobic polymer block and a hydrophilic polymer block, wherein the amphiphilic diblock copolymer comprises greater than 81% to about 95% by weight of the hydrophobic polymer block; and a protein having a molecular weight of up to or equal to about 300,000 Da. Various compositions comprising such filamentous-shaped nanocarrier particles, and methods of use for diagnosis and therapy are disclosed.
摘要翻译： 控制聚合物纳米载体包封的蛋白质颗粒的物理特性的方法包括改变或选择双乳液的初级乳液的全两亲双嵌段共聚物中的疏水性聚合物嵌段的重量百分数，冻融技术。 使用两亲二嵌段共聚物的冻融循环和分子量为至多300,000Da的蛋白质形成初级乳液。 疏水聚合物嵌段百分比的选择改变所得纳米颗粒的一种或多种特性，例如形状。 因此，一方面，生产丝状聚合物纳米载体包封的蛋白质（即活性酶）颗粒的方法包括使用（i）两亲性二嵌段共聚物（其分子量约为）的冷冻 - 解冻循环形成初级乳液 10,000至约100,000Da，并且包含疏水性聚合物嵌段和亲水性聚合物嵌段的共轭物，其中两亲性二嵌段共聚物包含大于疏水性聚合物嵌段重量的81％至约95％ 和分子量大于或等于约300,000Da的蛋白质。 公开了包含这种丝状纳米载体颗粒的各种组合物，以及用于诊断和治疗的方法。
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10.发明授权Compositions and methods for selective dissolution of nascent intravascular blood clots 有权用于选择性溶解新生血管内血块的组合物和方法公开(公告)号：US07041287B2
公开(公告)日：2006-05-09
申请号：US10611723
申请日：2003-07-01
CPC分类号： A61K9/0019 , A61K35/18 , A61K38/49
摘要： Compositions and methods for prevention and treatment of uncontrolled formation of intravascular fibrin clots, which are capable of selective dissolution of pathological nascent clots formed intravascularly, with minimal risk of unwanted dissolution of pre-existing hemostatic clots, are provided wherein fibrinolytic or anticoagulant drugs are biocompatibly coupled to red blood cell carriers.
摘要翻译： 提供了预防和治疗血管内纤维蛋白凝块的不受控制形成的组合物和方法，其能够选择性溶解血管内形成的病理性新生血栓，同时具有最小的预先存在的止血凝块溶解的风险，其中纤维蛋白溶解或抗凝血药物是生物相容性的 耦合到红细胞载体。
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