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1. 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'。

2. 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。

3. 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。

4. 发明申请

US20090292107A1 COMPOSITION AND METHOD TO ALTER LEAN BODY MASS AND BONE PROPERTIES IN A SUBJECT 审中-公开
标题翻译：组合物和方法，以提高身体质量和骨质量在一个主题
公开(公告)号：US20090292107A1
公开(公告)日：2009-11-26
申请号：US12018582
申请日：2008-01-23
申请人： Ruxandra Draghia-Akli , Robert J. Schwartz
发明人： Ruxandra Draghia-Akli , Robert J. Schwartz
IPC分类号： C07K14/00
CPC分类号： C07K14/60 , A61K38/25 , A61K48/00 , A61K48/0041 , A61K48/005 , A61K48/0083
摘要： The present invention pertains to a method for decreasing the body fat proportion, increasing lean body mass (“LBM”), increasing bone density, or improving the rate of bone healing, or all, of a subject. Overall, the embodiments of the invention can be accomplished by delivering a heterologous nucleic acid sequence encoding GHRH or functional biological equivalent thereof into the cells of the subject and allowing expression of the encoded gene to occur while the modified cells are within the subject. For instance, when such a nucleic acid sequence is delivered into the specific cells of the subject tissue specific constitutive expression is achieved. Furthermore, external regulation of the GHRH or functional biological equivalent thereof gene can be accomplished by utilizing inducible promoters that are regulated by molecular switch molecules, which are given to the subject. The preferred method to deliver the constitutive or inducible nucleic acid encoding sequences of GHRH or the functional biological equivalents thereof is directly into the cells of the subject by the process of in vivo electroporation. A decrease the body fat proportion and an increase in lean body mass (“LBM”), or both of a subject is achieved by the delivery of GHRH or functional biological equivalent thereof as described herein by into the subject as recombinant proteins. In addition, an increase in bone density and improvement in the rate of bone healing is also achieved.
摘要翻译：本发明涉及一种降低身体脂肪比例，增加瘦体重（“LBM”），增加骨密度或改善受试者的骨愈合速率或全身的方法。总的来说，本发明的实施方案可以通过将编码GHRH的异源核酸序列或其功能生物学等同物递送到受试者的细胞中并且允许在修饰的细胞在受试者内发生编码基因的表达来实现。例如，当这样的核酸序列被递送到对象组织的特定细胞中时，实现了特异性组成型表达。此外，GHRH或其功能生物等效基因的外部调节可以通过利用被给予受试者的由分子开关分子调节的诱导型启动子来实现。递送GHRH的组成型或诱导型核酸编码序列或其功能生物学等价物的优选方法通过体内电穿孔的方法直接进入受试者的细胞。通过将本文所述的GHRH或其功能生物学等同物作为重组蛋白递送到受试者中，可以降低身体脂肪比例和瘦体重增加（“LBM”）或两者。此外，还可以实现骨密度的增加和骨愈合速度的提高。

5. 发明授权

US07338656B2 Composition and method to alter lean body mass and bone properties in a subject 有权
标题翻译：在主体中改变瘦体重和骨骼特性的组合物和方法
公开(公告)号：US07338656B2
公开(公告)日：2008-03-04
申请号：US10281067
申请日：2002-10-25
申请人： Ruxandra Draghia-Akli , Robert J. Schwartz
发明人： Ruxandra Draghia-Akli , Robert J. Schwartz
IPC分类号： A61K48/00 , A01N63/00
CPC分类号： C07K14/60 , A61K38/25 , A61K48/00 , A61K48/0041 , A61K48/005 , A61K48/0083
摘要： A method for decreasing the body fat proportion, increasing lean body mass, increasing bone density, or improving the rate of bone healing, or all, of a subject. Embodiments of the invention include delivering a heterologous nucleic acid sequence encoding GHRH or functional biological equivalent thereof into the cells of the subject and allowing expression of the encoded gene to occur while the modified cells are within the subject.
摘要翻译：或减少身体脂肪比例，增加瘦体重，增加骨密度，或改善受试者骨骼愈合或全身的方法。本发明的实施方案包括将编码GHRH或其功能生物等价物的异源核酸序列递送到受试者的细胞中，并且允许编码基因在修饰的细胞在受试者内时发生。

6. 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。

7. 发明授权

US08927508B2 Antibody production elicited by a DNA vaccine delivered by electroporation 有权
标题翻译：由通过电穿孔递送的DNA疫苗引起的抗体生产
公开(公告)号：US08927508B2
公开(公告)日：2015-01-06
申请号：US12271603
申请日：2008-11-14
申请人： Ruxandra Draghia-Akli , Amir S. Khan
发明人： Ruxandra Draghia-Akli , Amir S. Khan
IPC分类号： A61K48/00 , C12N13/00 , A61K39/12 , A61K39/145 , C12N15/87 , A61K39/00
CPC分类号： A61K39/12 , A61K39/0011 , A61K39/145 , A61K48/00 , A61K2039/53 , A61K2039/54 , A61K2039/545 , A61K2039/55577 , A61K2039/70 , C12N13/00 , C12N15/87 , C12N2740/16134 , C12N2760/16134
摘要： There are provided methods of generating antibodies in a mammal against recombinant antigens using DNA plasmids capable of expressing said antigens in cells of said mammal, comprising: injecting into tissue of said mammal a DNA plasmid comprising an encoding sequence operably linked to a promoter, electroporating said tissue with an electroporation device capable of delivering an electrical pulse effective to electroporate cells of said tissue to allow entry of said DNA plasmid and expression of said antigen, and allowing said mammal to respond to said expressed antigen in order to generate antibodies to said antigen. Furthermore, there are provided methods of isolating antibodies specific against desired antigens wherein said antibodies are generated in a mammal using DNA plasmids capable of expressing said antigens.
摘要翻译：提供了在哺乳动物中使用能够在所述哺乳动物细胞中表达所述抗原的DNA质粒产生抗体的方法，包括：向所述哺乳动物的组织注射包含可操作地连接于启动子的编码序列的DNA质粒，将编码序列电穿孔所述具有电穿孔装置的组织，其能够递送有效地电穿孔所述组织的细胞的电脉冲，以允许所述DNA质粒的进入和所述抗原的表达，并允许所述哺乳动物响应所述表达的抗原以产生针对所述抗原的抗体。此外，提供了分离针对所需抗原特异性的抗体的方法，其中所述抗体在哺乳动物中使用能够表达所述抗原的DNA质粒产生。

8. 发明申请

US20110305664A1 NOVEL VACCINES AGAINST MULTIPLE SUBTYPES OF INFLUENZA VIRUS 有权
标题翻译：新鲜疫苗对多种流感病毒亚型
公开(公告)号：US20110305664A1
公开(公告)日：2011-12-15
申请号：US13158150
申请日：2011-06-10
申请人： Ruxandra Draghia-Akli , David B. Weiner , Jian Yan , Dominick Laddy
发明人： Ruxandra Draghia-Akli , David B. Weiner , Jian Yan , Dominick Laddy
IPC分类号： A61K39/145 , A61K38/20 , A61P31/16 , A61P37/04 , A61P31/12 , A61K39/395 , C12N15/63
CPC分类号： A61K39/145 , A61K9/0019 , A61K38/208 , A61K38/2086 , A61K39/12 , A61K47/34 , A61K2039/53 , A61K2039/54 , A61K2039/58 , A61K2039/70 , C07K14/005 , C12N7/00 , C12N2760/16034 , C12N2760/16122 , C12N2760/16134 , A61K2300/00
摘要： An aspect of the present invention is directed towards DNA plasmid vaccines capable of generating in a mammal an immune response against a plurality of influenza virus subtypes, comprising a DNA plasmid and a pharmaceutically acceptable excipient. The DNA plasmid is capable of expressing a consensus influenza antigen in a cell of the mammal in a quantity effective to elicit an immune response in the mammal, wherein the consensus influenza antigen comprises consensus hemagglutinin (HA), neuraminidase (NA), matrix protein, nucleoprotein, M2 ectodomain-nucleo-protein (M2e-NP), or a combination thereof. Preferably the consensus influenza antigen comprises HA, NA, M2e-NP, or a combination thereof. The DNA plasmid comprises a promoter operably linked to a coding sequence that encodes the consensus influenza antigen. Additionally, an aspect of the present invention includes methods of eliciting an immune response against a plurality of influenza virus subtypes in a mammal using the DNA plasmid vaccines provided.
摘要翻译：本发明的一个方面涉及能够在哺乳动物中产生针对多种流感病毒亚型的免疫应答的DNA质粒疫苗，其包含DNA质粒和药学上可接受的赋形剂。 DNA质粒能够以有效引发哺乳动物免疫应答的量在哺乳动物细胞中表达共有流感抗原，其中共有流感抗原包含共有血凝素（HA），神经氨酸酶（NA），基质蛋白，核蛋白，M2胞外域 - 核蛋白（M2e-NP）或其组合。优选地，共有流感抗原包含HA，NA，M2e-NP或其组合。 DNA质粒包含与编码共有流感抗原的编码序列可操作地连接的启动子。此外，本发明的一个方面包括使用提供的DNA质粒疫苗在哺乳动物中引发针对多种流感病毒亚型的免疫应答的方法。

9. 发明申请

US20090156787A1 ANTIBODY PRODUCTION ELICITED BY A DNA VACCINE DELIVERED BY ELECTROPORATION 有权
标题翻译：通过电泳提供的DNA疫苗有效的抗体生产
公开(公告)号：US20090156787A1
公开(公告)日：2009-06-18
申请号：US12271603
申请日：2008-11-14
申请人： Ruxandra Draghia-Akli , Amir S. Khan
发明人： Ruxandra Draghia-Akli , Amir S. Khan
IPC分类号： C07K16/18 , A61K39/395 , C07K16/08
CPC分类号： A61K39/12 , A61K39/0011 , A61K39/145 , A61K48/00 , A61K2039/53 , A61K2039/54 , A61K2039/545 , A61K2039/55577 , A61K2039/70 , C12N13/00 , C12N15/87 , C12N2740/16134 , C12N2760/16134
摘要： There are provided methods of generating antibodies in a mammal against recombinant antigens using DNA plasmids capable of expressing said antigens in cells of said mammal, comprising: injecting into tissue of said mammal a DNA plasmid comprising an encoding sequence operably linked to a promoter, electroporating said tissue with an electroporation device capable of delivering an electrical pulse effective to electroporate cells of said tissue to allow entry of said DNA plasmid and expression of said antigen, and allowing said mammal to respond to said expressed antigen in order to generate antibodies to said antigen. Furthermore, there are provided methods of isolating antibodies specific against desired antigens wherein said antibodies are generated in a mammal using DNA plasmids capable of expressing said antigens.
摘要翻译：提供了在哺乳动物中使用能够在所述哺乳动物细胞中表达所述抗原的DNA质粒产生抗体的方法，包括：向所述哺乳动物的组织注射包含可操作地连接于启动子的编码序列的DNA质粒，将编码序列电穿孔所述具有电穿孔装置的组织，其能够递送有效地电穿孔所述组织的细胞的电脉冲，以允许所述DNA质粒的进入和所述抗原的表达，并允许所述哺乳动物响应所述表达的抗原以产生针对所述抗原的抗体。此外，提供了分离针对所需抗原特异性的抗体的方法，其中所述抗体在哺乳动物中使用能够表达所述抗原的DNA质粒产生。

10. 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。

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