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1. 发明申请

US20090170748A1 Plasmid mediated supplementation for treating chronically ill subjects 有权
标题翻译：质粒介导的补充治疗慢性病患者
公开(公告)号：US20090170748A1
公开(公告)日：2009-07-02
申请号：US11726291
申请日：2007-03-21
申请人： Ruxandra Draghia-Akli , Robert H. Carpenter , Douglas R. Kern , Robert J. Schwartz , Glen King , Kevin Hahn , Malcolm K. Brenner
发明人： Ruxandra Draghia-Akli , Robert H. Carpenter , Douglas R. Kern , Robert J. Schwartz , Glen King , Kevin Hahn , Malcolm K. Brenner
IPC分类号： A61K38/00 , A61P7/06
CPC分类号： A61K38/25 , A61K48/00
摘要： The present invention pertains to compositions and methods for plasmid-mediated supplementation. The compositions and methods are useful for treating anemia and other effects that are commonly associated in cancer bearing animals. Overall, the embodiments of the invention can be accomplished by delivering an effective amount of a nucleic acid expression construct that encodes a GHRH or functional biological equivalent thereof into a tissue of an animal and allowing expression of the encoded gene in the animal. For example, when such a nucleic acid sequence is delivered into the specific cells of the animal tissue specific constitutive expression is achieved.
摘要翻译：本发明涉及用于质粒介导的补充的组合物和方法。组合物和方法可用于治疗贫血和通常与携带癌症的动物相关的其它作用。总的来说，本发明的实施方案可以通过将有效量的编码GHRH或其功能生物等价物的核酸表达构建体递送到动物的组织中并允许编码的基因在动物中表达来实现。例如，当这种核酸序列被递送到动物组织的特定细胞中时，实现了特异性组成型表达。

2. 发明授权

US08178504B2 Gene therapy expression of GHRH for increasing RBC count in subjects 有权
标题翻译：基因治疗GHRH表达增加受试者的RBC计数
公开(公告)号：US08178504B2
公开(公告)日：2012-05-15
申请号：US11726291
申请日：2007-03-21
申请人： Ruxandra Draghia-Akli , Robert H. Carpenter , Douglas R. Kern , Robert J. Schwartz , Glen King , Kevin Hahn , Malcolm K. Brenner
发明人： Ruxandra Draghia-Akli , Robert H. Carpenter , Douglas R. Kern , Robert J. Schwartz , Glen King , Kevin Hahn , Malcolm K. Brenner
IPC分类号： A61K48/00 , A01N63/00 , A01N65/00
CPC分类号： A61K38/25 , A61K48/00
摘要： The present invention pertains to compositions and methods useful for treating anemia and other effects that are commonly associated in cancer bearing animals. The invention is accomplished by delivering an effective amount of a nucleic acid expression construct that encodes a GHRH or functional biological equivalent thereof into a tissue of an animal and allowing expression of the encoded gene in the animal.
摘要翻译：本发明涉及可用于治疗贫血的组合物和方法以及通常与携带癌症的动物相关的其它作用。本发明通过将有效量的编码GHRH或其功能生物等价物的核酸表达构建体递送到动物的组织中并允许编码的基因在动物中表达来实现。

3. 发明授权

US07241744B2 Treating anemia in subjects by administration of plasmids encoding growth hormone releasing hormone 有权
标题翻译：通过施用编码生长激素释放激素的质粒治疗受试者的贫血
公开(公告)号：US07241744B2
公开(公告)日：2007-07-10
申请号：US10315907
申请日：2002-12-10
申请人： Ruxandra Draghia-Akli , Robert H. Carpenter , Douglas R. Kern , Robert J. Schwartz , Glen King , Kevin Hahn , Malcolm K. Brenner
发明人： Ruxandra Draghia-Akli , Robert H. Carpenter , Douglas R. Kern , Robert J. Schwartz , Glen King , Kevin Hahn , Malcolm K. Brenner
IPC分类号： A01N43/04 , A61K31/70 , A01N63/00 , A01N65/00 , C07H21/02 , C07H21/04 , A61K38/24 , C07K1/00 , C07K17/00
CPC分类号： A61K38/25 , A61K48/00
摘要： The present invention pertains to compositions and methods for plasmid-mediated supplementation. The compositions and method are useful for retarding the growth of the tumor, and retarding cachexia, wasting, anemia and other effects that are commonly associated in cancer bearing animals. Overall, the embodiments of the invention can be accomplished by delivering an effective amount of a nucleic acid expression construct that encodes a GHRH or functional biological equivalent thereof into a tissue of an animal and allowing expression of the encoded. gene in the animal. For example, when such a nucleic acid sequence is delivered into the specific cells of the tissue specific constitutive expression is achieved.
摘要翻译：本发明涉及用于质粒介导的补充的组合物和方法。组合物和方法可用于延缓肿瘤的生长，并缓解通常与携带癌症的动物相关的恶病质，浪费，贫血和其它作用。总的来说，本发明的实施方案可以通过将有效量的编码GHRH或其功能生物等价物的核酸表达构建体递送到动物的组织中并允许编码的表达来实现。基因在动物体内。例如，当这样的核酸序列被递送到组织的特定细胞中时，实现了特异性组成型表达。

4. 发明授权

US07664545B2 Electrode assembly for constant-current electroporation and use 有权
标题翻译：用于恒流电穿孔和使用的电极组件
公开(公告)号：US07664545B2
公开(公告)日：2010-02-16
申请号：US11495021
申请日：2006-07-28
申请人： Allan Westersten , William R. Wilkinson , Ruxandra Draghia-Akli , Robert H. Carpenter , Douglas R. Kern
发明人： Allan Westersten , William R. Wilkinson , Ruxandra Draghia-Akli , Robert H. Carpenter , Douglas R. Kern
IPC分类号： A61N1/30
CPC分类号： A61N1/327
摘要： The present invention relates to a modular electrode system, and its use, for facilitating the introduction of a macromolecule into cells of a selected tissue in a body or plant. The modular electrode system comprises a non-symmetrically arranged plurality of needle electrodes; a hypodermic needle; an electrical connector that provides a conductive link from a programmable constant-current pulse controller to the plurality of needle electrodes; and a power source. In a preferred embodiment of the present invention, an operator can grasp the plurality of needle electrodes that are mounted on a support structure and firmly insert the them into the selected tissue in a body or plant. The macromolecules are then delivered via the hypodermic needle into the selected tissue. The programmable constant-current pulse controller is activated and constant-current electrical pulse is applied to the plurality of needle electrodes. The applied constant-current electrical pulse facilitates the introduction of the macromolecule into the cell between the plurality of electrodes. Cell death due to overheating of cells is minimized by limiting the power dissipation in the tissue by virtue of constant-current pulses.
摘要翻译：本发明涉及一种模块化电极系统及其用途，用于促进将大分子引入体内或选定组织中的细胞中。模块化电极系统包括非对称布置的多个针电极; 皮下注射针电连接器，其从可编程恒定电流脉冲控制器提供到多个针电极的导电连接; 和电源。在本发明的优选实施例中，操作者可以抓住安装在支撑结构上的多个针电极并将其牢固地插入到身体或植物中的所选择的组织中。然后通过皮下注射针将大分子递送到选定的组织中。可编程恒定电流脉冲控制器被激活，并且多个针电极施加恒流电脉冲。施加的恒流电脉冲有助于将大分子引入多个电极之间的电池中。由于通过恒定电流脉冲限制组织中的功率消耗，使由于细胞过热引起的细胞死亡被最小化。

5. 发明授权

US07245963B2 Electrode assembly for constant-current electroporation and use 有权
标题翻译：用于恒流电穿孔和使用的电极组件
公开(公告)号：US07245963B2
公开(公告)日：2007-07-17
申请号：US10360768
申请日：2002-03-07
申请人： Ruxandra Draghia-Akli , Robert H. Carpenter , Douglas R. Kern , Allan Westersten , William R. Wilkinson
发明人： Ruxandra Draghia-Akli , Robert H. Carpenter , Douglas R. Kern , Allan Westersten , William R. Wilkinson
IPC分类号： A61N1/30
CPC分类号： A61N1/327
摘要： The present invention relates to a modular electrode system, and its use, for facilitating the introduction of a macromolecule into cells of a selected tissue in a body or plant. The modular electrode system comprises a plurality of needle electrodes; a hypodermic needle; an electrical connector that provides a conductive link from a programmable constant-current pulse controller to the plurality of needle electrodes; and a power source. In a preferred embodiment of the present invention, an operator can grasp the plurality of needle electrodes that are mounted on a support structure and firmly insert the them into the selected tissue in a body or plant. The macromolecules are then delivered via the hypodermic needle into the selected tissue. The programmable constant-current pulse controller is activated and constant-current electrical pulse is applied to the plurality of needle electrodes. The applied constant-current electrical pulse facilitates the introduction of the macromolecule into the cell between the plurality of electrodes. Cell death due to overheating of cells is minimized by limiting the power dissipation in the tissue by virtue of constant-current pulses.
摘要翻译：本发明涉及一种模块化电极系统及其用途，用于促进将大分子引入体内或选定组织中的细胞中。模块化电极系统包括多个针电极; 皮下注射针电连接器，其从可编程恒定电流脉冲控制器提供到多个针电极的导电连接; 和电源。在本发明的优选实施例中，操作者可以抓住安装在支撑结构上的多个针电极并将其牢固地插入到身体或植物中的所选择的组织中。然后通过皮下注射针将大分子递送到选定的组织中。可编程恒定电流脉冲控制器被激活，并且多个针电极施加恒流电脉冲。施加的恒流电脉冲有助于将大分子引入多个电极之间的电池中。由于通过恒定电流脉冲限制组织中的功率消耗，使由于细胞过热引起的细胞死亡被最小化。

6. 发明授权

US07316925B2 Codon optimized synthetic plasmids 有权
标题翻译：密码子优化的合成质粒
公开(公告)号：US07316925B2
公开(公告)日：2008-01-08
申请号：US10619939
申请日：2003-07-15
申请人： Ruxandra Draghia-Akli , Ronald V. Abruzzese , Douglas R. Kern
发明人： Ruxandra Draghia-Akli , Ronald V. Abruzzese , Douglas R. Kern
IPC分类号： C12N15/85 , C07H21/04 , A61K48/00
CPC分类号： C12N15/67 , A61K48/00 , C07K14/60 , C12N15/85 , C12N2830/008 , C12N2830/15 , C12N2840/20 , C12N2840/203
摘要： One aspect of the current invention is an optimized synthetic mammalian expression plasmid (e.g. pAV0201). This new plasmid comprise a therapeutic element, and a replication element. The therapeutic element of the new plasmid comprises a eukaryotic promoter; a 5′ untranslated region (“UTR”); a codon-optimized-eukaryotic therapeutic gene sequence; and a poly adenylation signal. The therapeutic elements of this plasmid are operatively linked and located in a first operatively-linked arrangement. Additionally, the optimized synthetic mammalian expression plasmid comprises replication elements, wherein the replication elements are operatively linked and located in a second operatively-linked arrangement. The replication elements comprise a selectable marker gene promoter, a ribosomal binding site, and an origin of replication. The first-operatively-linked arrangement and the second-operatively-linked arrangement comprise a circular structure of the codon optimized synthetic mammalian expression plasmid.
摘要翻译：本发明的一个方面是优化的合成哺乳动物表达质粒（例如pAV0201）。该新质粒包含治疗元件和复制元件。新质粒的治疗元件包含真核启动子; 5'非翻译区（“UTR”）; 密码子优化的真核治疗基因序列; 和聚腺苷酸化信号。该质粒的治疗元件可操作地连接并位于第一可操作连接的布置中。此外，优化的合成哺乳动物表达质粒包含复制元件，其中复制元件可操作地连接并位于第二可操作连接的布置中。复制元件包括选择性标记基因启动子，核糖体结合位点和复制起点。第一操作连接的排列和第二操作连接的排列包括密码子优化的合成哺乳动物表达质粒的圆形结构。

7. 发明申请

US20080194511A1 CODON OPTIMIZED SYNTHETIC PLASMIDS 审中-公开
标题翻译： CODON优化合成PLASMIDS
公开(公告)号：US20080194511A1
公开(公告)日：2008-08-14
申请号：US11941876
申请日：2007-11-16
申请人： Ruxandra Draghia-Akli , Ronald V. Abruzzese , Douglas R. Kern
发明人： Ruxandra Draghia-Akli , Ronald V. Abruzzese , Douglas R. Kern
IPC分类号： A61K31/711
CPC分类号： C12N15/67 , A61K48/00 , C07K14/60 , C12N15/85 , C12N2830/008 , C12N2830/15 , C12N2840/20 , C12N2840/203
摘要： One aspect of the current invention is an optimized synthetic mammalian expression plasmid (e.g. pAV0201). This new plasmid comprise a therapeutic element, and a replication element. The therapeutic element of the new plasmid comprises a eukaryotic promoter; a 5′ untranslated region (“UTR”); a codon-optimized-eukaryotic therapeutic gene sequence; and a poly adenylation signal. The therapeutic elements of this plasmid are operatively linked and located in a first operatively-linked arrangement. Additionally, the optimized synthetic mammalian expression plasmid comprises replication elements, wherein the replication elements are operatively linked and located in a second operatively-linked arrangement. The replication elements comprise a selectable marker gene promoter, a ribosomal binding site, and an origin of replication. The first-operatively-linked arrangement and the second-operatively-linked arrangement comprise a circular structure of the codon optimized synthetic mammalian expression plasmid.
摘要翻译：本发明的一个方面是优化的合成哺乳动物表达质粒（例如pAV0201）。该新质粒包含治疗元件和复制元件。新质粒的治疗元件包含真核启动子; 5'非翻译区（“UTR”）; 密码子优化的真核治疗基因序列; 和聚腺苷酸化信号。该质粒的治疗元件可操作地连接并位于第一可操作连接的布置中。此外，优化的合成哺乳动物表达质粒包含复制元件，其中复制元件可操作地连接并位于第二可操作连接的布置中。复制元件包括选择性标记基因启动子，核糖体结合位点和复制起点。第一操作连接的排列和第二操作连接的排列包括密码子优化的合成哺乳动物表达质粒的圆形结构。

8. 发明申请

US20090005333A1 REDUCING CULLING IN HERD ANIMALS GROWTH HORMONE RELEASING HORMONE (GHRH) 审中-公开
标题翻译：减少激素在动物生长激素释放激素（GHRH）
公开(公告)号：US20090005333A1
公开(公告)日：2009-01-01
申请号：US12044779
申请日：2008-03-07
申请人： Patricia A. Brown , Ruxandra Draghia-Akli , Robert H. Carpenter
发明人： Patricia A. Brown , Ruxandra Draghia-Akli , Robert H. Carpenter
IPC分类号： A61K31/711 , A61P43/00
CPC分类号： A61K38/25 , A61K48/0016 , A61K48/0075 , A61K48/0083 , C07K14/60
摘要： One aspect of the current invention is a method of decreasing an involuntary cull rate in farm animals, wherein the involuntary cull results from infection, disease, morbidity, or mortality. Additionally, milk production, animal welfare, and body condition scores are improved by utilizing methodology that administers the isolated nucleic acid expression construct encoding a GHRH or functional biological equivalent to an animal through a parenteral route of administration. Following a single dose of nucleic acid expression vector, animals are healthier and effects are demonstrated long term without additional administration(s) of the expression construct.
摘要翻译：本发明的一个方面是减少农场动物中的非自愿剔除率的方法，其中非自愿宰杀来自感染，疾病，发病率或死亡率。此外，通过使用通过肠胃外给药途径施用编码GHRH的分离的核酸表达构建体或与动物的功能生物等价物的方法，提高了产奶量，动物福利和身体状况得分。在单剂量的核酸表达载体之后，动物更健康，并且长期表现效果，而没有额外施用表达构建体。

9. 发明授权

US08209006B2 Constant current electroporation device and methods of use 有权
标题翻译：恒流电穿孔装置及其使用方法
公开(公告)号：US08209006B2
公开(公告)日：2012-06-26
申请号：US10657725
申请日：2003-09-08
申请人： Louis C. Smith , Ruxandra Draghia-Akli , Amir S. Khan , Robert H. Carpenter , Jeff Darnell
发明人： Louis C. Smith , Ruxandra Draghia-Akli , Amir S. Khan , Robert H. Carpenter , Jeff Darnell
IPC分类号： A61N1/30
CPC分类号： A61N1/0412 , A61N1/0476 , A61N1/327
摘要： An electroporation device which may be used to effectively facilitate the introduction of a macromolecule into cells of a selected tissue in a body or plant. The electroporation device comprises an electro-kinetic device (“EKD”) whose operation is specified by software or firmware. The EKD produces a series of programmable constant-current pulse patterns between electrodes in an array based on user control and input of the pulse parameters and allows the storage and acquisition of current waveform data. The electroporation device also comprises a replaceable electrode disk having an array of needle electrodes, a central injection channel for an injection needle, and a removable guide disk.
摘要翻译：可用于有效促进将大分子引入身体或植物中选定组织的细胞中的电穿孔装置。电穿孔装置包括其动作由软件或固件指定的电动装置（“EKD”）。 EKD基于用户控制和输入脉冲参数，在阵列中的电极之间产生一系列可编程恒定电流脉冲模式，并允许存储和采集电流波形数据。电穿孔装置还包括具有针电极阵列的可替换电极盘，用于注射针的中心注射通道和可移除引导盘。

10. 发明授权

US06423693B1 Growth hormone releasing hormone expression system and methods of use, including use in animals 失效
标题翻译：生长激素释放激素表达系统及使用方法，包括用于动物
公开(公告)号：US06423693B1
公开(公告)日：2002-07-23
申请号：US09122171
申请日：1998-07-24
申请人： Robert J. Schwartz , Ruxandra Draghia-Akli , Xuyang Li , Eric M. Eastman
发明人： Robert J. Schwartz , Ruxandra Draghia-Akli , Xuyang Li , Eric M. Eastman
IPC分类号： A61K3170
CPC分类号： A01K67/0275 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/02 , A01K2267/03 , A61K38/25 , A61K48/00 , A61K48/0008 , A61K48/0058 , C07K14/60 , C07K2319/00 , C12N15/85 , C12N15/8509 , C12N2799/021
摘要： Vectors which establish controlled expression of recombinant GHRH genes within tissues at certain levels. The vector includes a 5′ flanking region which includes necessary sequences for expression of a nucleic acid cassette, a 3′ flanking region including a 3′UTR and/or 3′NCR, and a linker which connects the 5′ flanking region to a nucleic acid sequence. The linker has a position for inserting a nucleic acid cassette. The linker does not contain the coding sequence of a gene that the linker is naturally associated with. The 3′ flanking region is 3′ to the position for inserting the nucleic acid cassette.
摘要翻译：在某些水平的组织内建立重组GHRH基因的受控表达的载体。载体包括5'侧翼区，其包含用于表达核酸盒的必需序列，包含3'UTR和/或3'NCR的3'侧翼区和将5'侧翼区连接到核酸的连接体酸序列。接头具有用于插入核酸盒的位置。接头不包含接头天然相关基因的编码序列。 3'侧翼区域为插入核酸盒的位置3'。

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