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1. 发明申请

US20080199957A1 ENHANCED TRANSPORT USING MEMBRANE DISRUPTIVE AGENTS 有权
标题翻译：使用薄膜破坏剂加强运输
公开(公告)号：US20080199957A1
公开(公告)日：2008-08-21
申请号：US12105983
申请日：2008-04-18
申请人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
发明人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
IPC分类号： C12N5/06
CPC分类号： A61K47/481 , A61K41/0028 , A61K41/0047 , A61K47/48376 , A61K47/6801
摘要： Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontophoresis, and/or electrophoresis can also be used with the disrupting agents.
摘要翻译：描述了用于从细胞，细胞内的细胞室或通过细胞层或屏障转运或释放治疗和诊断试剂或代谢物或其它分析物的组合物和方法。组合物包括膜屏障转运增强剂，并且通常与增强剂和/或暴露于刺激物一起施用以实现破坏或改变渗透性，运输或释放。在优选的实施方案中，组合物包括响应于内体中的低pH而破坏内体膜的化合物，但是与细胞膜相对无活性的化合物，直接或间接地与治疗剂或诊断剂偶联。还可以使用其它破坏剂，对除了pH之外的刺激和/或增强剂如光，电刺激，电磁刺激，超声，温度或其组合都有反应。这些化合物可以通过离子，共价键或H键连接到待递送的试剂上，或者与配制剂形成配合物。待递送的药剂可以是治疗和/或诊断剂。增强交付如超声波，离子电渗疗法和/或电泳的治疗也可与破坏剂一起使用。

2. 发明申请

US20070224241A1 TEMPERATURE- AND pH-RESPONSIVE POLYMER COMPOSITIONS 有权
标题翻译：温度和pH响应聚合物组合物
公开(公告)号：US20070224241A1
公开(公告)日：2007-09-27
申请号：US11687522
申请日：2007-03-16
申请人： Patrick Stayton , Allan Hoffman , Xiangchun Yin , Lakeshia Taite , Jessica Garbern
发明人： Patrick Stayton , Allan Hoffman , Xiangchun Yin , Lakeshia Taite , Jessica Garbern
IPC分类号： A61F2/02 , C08L61/20
CPC分类号： C08L53/00 , A61K47/58 , A61K47/6903 , A61K47/6907 , A61K47/6933 , B82Y5/00 , C08F8/00 , C08F220/04 , C08F220/06 , C08F220/54 , C08F220/58 , C08F293/00 , C08F293/005 , C08F2438/03 , C08F2800/20 , C08F2810/20 , C08L2312/00 , C08L2666/02 , C08L2666/04
摘要： Temperature- and pH-responsive copolymer compositions, and drug delivery devices, conjugates, nanoparticles, and micelles that include the compositions.
摘要翻译：温度和pH响应共聚物组合物，以及包括组合物的药物递送装置，缀合物，纳米颗粒和胶束。

3. 发明授权

US5466589A Coated substrates employing oriented layers of mutant heme proteins and methods of making and using same 失效
标题翻译：使用突变血红素蛋白取向层的涂覆底物及其制造和使用方法
公开(公告)号：US5466589A
公开(公告)日：1995-11-14
申请号：US945291
申请日：1992-09-11
申请人： Jill M. Olinger , Stephen G. Sligar , Mark A. McLean , Paul W. Bohn , Patrick Stayton
发明人： Jill M. Olinger , Stephen G. Sligar , Mark A. McLean , Paul W. Bohn , Patrick Stayton
IPC分类号： C07K14/80 , C07K14/805 , C12N15/10 , C12N11/02 , C12M1/14 , G01N21/41 , G01N27/327
CPC分类号： C12N15/1058 , C07K14/80 , C07K14/805 , Y10S435/808 , Y10S435/817 , Y10S530/81
摘要： The present invention is directed to coated substrates having a coating of biological macromolecules, preferably proteins, which are capable of being immobilized on a substrate surface and have a marker. These proteins usually are mutant proteins obtained by mutagenesis of the gene encoding a random positioning protein. When a mutant protein molecule is immobilized on the substrate, the marker of the mutant protein molecule is in a select spatial relationship with both the substrate and the markers of adjacent protein molecules. A substrate coated with an oriented layer of the mutant proteins exhibits improved or different properties when compared to a substrate having a randomly positioned layer of proteins thereon.
摘要翻译：本发明涉及具有能够固定在基材表面上并具有标记物的生物大分子（优选蛋白质）的涂层的涂布基材。这些蛋白质通常是通过编码随机定位蛋白质的基因的诱变获得的突变蛋白质。当突变蛋白分子被固定在底物上时，突变蛋白分子的标记物与底物和相邻蛋白质分子的标记物处于选择的空间关系。当与其上具有随机定位的蛋白质层的底物相比时，涂覆有突变蛋白的取向层的底物表现出改善的或不同的性质。

4. 发明授权

US08846106B2 Enhanced transport using membrane disruptive agents 有权
标题翻译：增强运输使用膜破坏剂
公开(公告)号：US08846106B2
公开(公告)日：2014-09-30
申请号：US13182756
申请日：2011-07-14
申请人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
发明人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
IPC分类号： A61K9/14 , A61K9/16 , A61K47/00 , A61K41/00 , A61K47/48
CPC分类号： A61K47/481 , A61K41/0028 , A61K41/0047 , A61K47/48376 , A61K47/6801
摘要： Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and/or electrophoresis can also be used with the disrupting agents.
摘要翻译：描述了用于从细胞，细胞内的细胞室或通过细胞层或屏障转运或释放治疗和诊断试剂或代谢物或其它分析物的组合物和方法。组合物包括膜屏障转运增强剂，并且通常与增强剂和/或暴露于刺激物一起施用以实现破坏或改变渗透性，运输或释放。在优选的实施方案中，组合物包括响应于内体中的低pH而破坏内体膜的化合物，但是与细胞膜相对无活性的化合物，直接或间接地与治疗剂或诊断剂偶联。还可以使用其它破坏剂，对除了pH之外的刺激和/或增强剂如光，电刺激，电磁刺激，超声，温度或其组合都有反应。这些化合物可以通过离子，共价键或H键连接到待递送的试剂上，或者与配制剂形成配合物。待递送的药剂可以是治疗和/或诊断剂。增强递送的治疗如超声波，离子分离和/或电泳也可与破坏剂一起使用。

5. 发明授权

US08003129B2 Enhanced transport using membrane disruptive agents 有权
标题翻译：增强运输使用膜破坏剂
公开(公告)号：US08003129B2
公开(公告)日：2011-08-23
申请号：US12105983
申请日：2008-04-18
申请人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
发明人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
IPC分类号： A61K9/14 , A61K9/16 , A61K47/00 , A61K9/127
CPC分类号： A61K47/481 , A61K41/0028 , A61K41/0047 , A61K47/48376 , A61K47/6801
摘要： Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontophoresis, and/or electrophoresis can also be used with the disrupting agents.
摘要翻译：描述了用于从细胞，细胞内的细胞室或通过细胞层或屏障转运或释放治疗和诊断试剂或代谢物或其它分析物的组合物和方法。组合物包括膜屏障转运增强剂，并且通常与增强剂和/或暴露于刺激物一起施用以实现破坏或改变渗透性，运输或释放。在优选的实施方案中，组合物包括响应于内体中的低pH而破坏内体膜的化合物，但是与细胞膜相对无活性的化合物，直接或间接地与治疗剂或诊断剂偶联。还可以使用其它破坏剂，对除了pH之外的刺激和/或增强剂如光，电刺激，电磁刺激，超声，温度或其组合都有反应。这些化合物可以通过离子，共价键或H键连接到待递送的试剂上，或者与配制剂形成配合物。待递送的药剂可以是治疗和/或诊断剂。增强交付如超声波，离子电渗疗法和/或电泳的治疗也可与破坏剂一起使用。

6. 发明授权

US07374778B2 Enhanced transport using membrane disruptive agents 有权
标题翻译：增强运输使用膜破坏剂
公开(公告)号：US07374778B2
公开(公告)日：2008-05-20
申请号：US10857626
申请日：2004-05-28
申请人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
发明人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
IPC分类号： A61K9/127 , A61K9/14 , A61K9/16 , A61K47/00
CPC分类号： A61K47/481 , A61K41/0028 , A61K41/0047 , A61K47/48376 , A61K47/6801
摘要： Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and/or electrophereis can also be used with the disrupting agents.
摘要翻译：描述了用于从细胞，细胞内的细胞室或通过细胞层或屏障转运或释放治疗和诊断试剂或代谢物或其它分析物的组合物和方法。组合物包括膜屏障转运增强剂，并且通常与增强剂和/或暴露于刺激物一起施用以实现破坏或改变渗透性，运输或释放。在优选的实施方案中，组合物包括响应于内体中的低pH而破坏内体膜的化合物，但是与细胞膜相对无活性的化合物，直接或间接地与治疗剂或诊断剂偶联。还可以使用其它破坏剂，对除了pH之外的刺激和/或增强剂如光，电刺激，电磁刺激，超声，温度或其组合都有反应。这些化合物可以通过离子，共价键或H键连接到待递送的试剂上，或者与配制剂形成配合物。待递送的药剂可以是治疗和/或诊断剂。还可以与破坏剂一起使用增强交付如超声，离子层析和/或电穿孔的处理。

7. 发明申请

US20110288238A1 ENHANCED TRANSPORT USING MEMBRANE DISRUPTIVE AGENTS 有权
标题翻译：使用薄膜破坏剂加强运输
公开(公告)号：US20110288238A1
公开(公告)日：2011-11-24
申请号：US13182756
申请日：2011-07-14
申请人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
发明人： Allan S. Hoffman , Patrick Stayton , Oliver W. Press , Niren Murthy , Chantal Lackey Reed , Lawrence A. Crum , Pierre D. Mourad , Tyrone M. Porter , David Tirrell
IPC分类号： C08F220/06 , C08F265/02 , C08F299/00
CPC分类号： A61K47/481 , A61K41/0028 , A61K41/0047 , A61K47/48376 , A61K47/6801
摘要： Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and/or electrophoresis can also be used with the disrupting agents.
摘要翻译：描述了用于从细胞，细胞内的细胞室或通过细胞层或屏障转运或释放治疗和诊断试剂或代谢物或其它分析物的组合物和方法。组合物包括膜屏障转运增强剂，并且通常与增强剂和/或暴露于刺激物一起施用以实现破坏或改变渗透性，运输或释放。在优选的实施方案中，组合物包括响应于内体中的低pH而破坏内体膜的化合物，但是与细胞膜相对无活性的化合物，直接或间接地与治疗剂或诊断剂偶联。还可以使用其它破坏剂，对除了pH之外的刺激和/或增强剂如光，电刺激，电磁刺激，超声波，温度或其组合都有反应。这些化合物可以通过离子，共价键或H键连接到待递送的试剂上，或者与配制剂形成配合物。待递送的药剂可以是治疗和/或诊断剂。增强递送的治疗如超声波，离子分离和/或电泳也可与破坏剂一起使用。

8. 发明申请

US20060281677A1 Compositions and methods for intracellular delivery of biotinylated cargo 失效
公开(公告)号：US20060281677A1
公开(公告)日：2006-12-14
申请号：US11150588
申请日：2005-06-10
申请人： Brian Albarran , Patrick Stayton , Richard To
发明人： Brian Albarran , Patrick Stayton , Richard To
IPC分类号： A61K38/16 , A61K38/17 , A61K31/4188
CPC分类号： B82Y5/00 , A61K31/4188 , A61K47/645 , A61K47/665 , Y10S530/815
摘要： The invention provides compositions for intracellular delivery of biotinylated cargo. The compositions comprise a complex formed between (a) a fusion protein comprising a protein transduction domain linked to streptavidin and (b) a biotinylated cargo for intracellular delivery. In some embodiments, the protein transduction domain comprises the protein transduction domain of the Human Immunodeficiency Virus type 1 (HIV-1) TAT protein. The complex may further comprise a biotinylated endosomal releasing polymer, such as a poly(propylacrylic acid) polymer. The invention also provides methods for obtaining intracellular delivery of biotinylated cargo and methods for obtaining cytoplasmic delivery of biotinylated cargo.

9. 发明申请

US20060127925A1 Stimuli-responsive polymer conjugates and related methods 有权
标题翻译：刺激响应聚合物共轭物和相关方法
公开(公告)号：US20060127925A1
公开(公告)日：2006-06-15
申请号：US11197771
申请日：2005-08-03
申请人： Patrick Stayton , Allan Hoffman , Noah Malmstadt , Tsuyoshi Shimoboji , Samarth Kulkarni
发明人： Patrick Stayton , Allan Hoffman , Noah Malmstadt , Tsuyoshi Shimoboji , Samarth Kulkarni
IPC分类号： C12Q1/68 , G01N33/53 , C12M1/34 , B05D3/02
CPC分类号： G01N33/54353 , C12N15/1006 , C12N15/1034 , G01N33/54346 , G01N33/545
摘要： Conjugates that include polymers that are reversibly self-associative in response to a stimulus and methods for using the conjugates.
摘要翻译：包括响应于刺激的可逆地自缔合的聚合物和使用共轭物的共轭物。

10. 发明申请

US20140235790A1 CARBOHYDRATE-BASED COMPOSITIONS AND METHODS FOR TARGETED DRUG DELIVERY 审中-公开
标题翻译：基于碳酸氢盐的组合物和用于靶向药物递送的方法
公开(公告)号：US20140235790A1
公开(公告)日：2014-08-21
申请号：US14125289
申请日：2012-06-11
申请人： Patrick Stayton , Matthew Manganiello , Anthony Convertine , Daniel M. Ratner , Yu-Hua Chow , Eun-Ho Song , Bilal Ghosn , Lynn Schnapp , Salka Keller , Debashish Roy
发明人： Patrick Stayton , Matthew Manganiello , Anthony Convertine , Daniel M. Ratner , Yu-Hua Chow , Eun-Ho Song , Bilal Ghosn , Lynn Schnapp , Salka Keller , Debashish Roy
IPC分类号： A61K47/48 , A61K51/06 , A61K49/12 , A61K49/00
CPC分类号： A61K47/58 , C08F293/005 , C08F2438/03
摘要： Provided herein are compositions and methods for intracellular delivery. The compositions are polymer compositions in which the polymer serves as a carrier for therapeutic and/or diagnostic agents. The polymer compositions are effective in targeted delivery of therapeutic and/or diagnostic agents to a cell. The polymer compositions include a targeting moiety that includes carbohydrate groups that effectively target specific cell surface receptors. The polymer compositions also include an agent binding moiety that effectively associates the therapeutic and/or diagnostic agent to be delivered to the cell.
摘要翻译：本文提供了用于细胞内递送的组合物和方法。组合物是其中聚合物用作治疗剂和/或诊断剂的载体的聚合物组合物。聚合物组合物有效地向细胞靶向递送治疗剂和/或诊断剂。聚合物组合物包括靶向部分，其包括有效靶向特定细胞表面受体的碳水化合物基团。聚合物组合物还包括能够将待递送至细胞的治疗剂和/或诊断剂有效结合的药剂结合部分。

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