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11. 发明申请

US20130209405A1 RECOMBINANT BACTERIUM TO DECREASE TUMOR GROWTH 有权
标题翻译：重组细菌减少肿瘤生长
公开(公告)号：US20130209405A1
公开(公告)日：2013-08-15
申请号：US13700591
申请日：2011-05-31
申请人： Roy Curtiss, III , Wei Kong
发明人： Roy Curtiss, III , Wei Kong
IPC分类号： C12N15/74
CPC分类号： C12N15/74 , A61K35/74 , C12N1/36 , C12R1/42
摘要： A recombinant bacterium capable of reducing tumor growth is provided, wherein said recombinant bacterium is capable of: a. increased expression of a nucleic acid encoding a chemoreceptor that directs chemotaxis towards tumors, b. accumulation in a quiescent tumor, c. hyper-invasion of a tumor, d. reduced fitness in normal tissue, e. enhanced stimulation of the host innate immune responses, f. delivering a tumor specific DNA vaccine vector to a tumor cell, and g. increased bacterium-induced host programmed cell death.
摘要翻译：提供能够降低肿瘤生长的重组细菌，其中所述重组细菌能够：a。增加编码趋化性朝向肿瘤的化学感受器的核酸的表达，b。积聚在静止的肿瘤中，c。肿瘤超侵袭，d。降低正常组织的适应性，增强对宿主先天免疫反应的刺激，f。将肿瘤特异性DNA疫苗载体递送至肿瘤细胞，g。增加细菌诱导的宿主程序性细胞死亡。

12. 发明授权

US07083794B2 Recombinant vaccines comprising immunogenic attenuated bacteria having RpoS positive phenotype 有权
标题翻译：包含具有RpoS阳性表型的免疫原性减毒细菌的重组疫苗
公开(公告)号：US07083794B2
公开(公告)日：2006-08-01
申请号：US10138239
申请日：2002-05-03
申请人： Roy Curtiss, III , Cheryl A. Nickerson
发明人： Roy Curtiss, III , Cheryl A. Nickerson
IPC分类号： A61K39/02 , A61K39/112 , C12N15/74 , C12N1/21
CPC分类号： A61K39/12 , A61K35/74 , A61K39/0006 , A61K39/0275 , A61K39/292 , A61K39/35 , A61K48/00 , A61K2039/522 , A61K2039/523 , A61K2039/542 , A61K2039/543 , A61K2039/545 , A61K2039/57 , C12N1/22 , C12N2730/10134 , Y02A50/482 , Y02A50/484 , Y10S435/879 , Y10S435/897 , A61K2300/00
摘要： Attenuated immunogenic bacteria having an RpoS+ phenotype, in particular, Salmonella enterica serotype Typhi having an RpoS+ phenotype and methods therefor are disclosed. The Salmonella have in addition to an RpoS+ phenotype, an inactivating mutation in one or more genes which render the microbe attenuated, and a recombinant gene capable of expressing a desired protein. The Salmonella are attenuated and have high immunogenicity so that they can be used in vaccines and as delivery vehicles for genes and gene products. Also disclosed are methods for preparing the vaccine delivery vehicles.
摘要翻译：公开了具有RpoS + / / SUP表型的减毒免疫原细菌，特别是具有RpoS +表型的肠炎沙门氏菌血清型Typhi及其方法。沙门氏菌除了具有RpoS 表型外，一种或多种使微生物减毒的基因中的失活突变，以及能够表达所需蛋白质的重组基因。沙门氏菌减毒，免疫原性高，可用于疫苗和作为基因和基因产物的递送载体。还公开了制备疫苗递送载体的方法。

13. 发明授权

US06872547B1 Functional balanced-lethal host-vector systems 有权
标题翻译：功能平衡致命的宿主载体系统
公开(公告)号：US06872547B1
公开(公告)日：2005-03-29
申请号：US09686499
申请日：2000-10-11
申请人： Roy Curtiss, III
发明人： Roy Curtiss, III
IPC分类号： A61K39/00 , A61K39/02 , A61K39/112 , A61K48/00 , C07K14/24 , C12N15/70 , C12N15/74 , C12P21/06 , C12N1/12 , C12N1/20 , A61K39/108
CPC分类号： C12N15/74 , A61K39/00 , A61K39/0258 , A61K39/0275 , A61K48/0008 , A61K2039/522 , A61K2039/53 , C07K14/24 , C12N15/70 , Y02A50/474 , Y02A50/482
摘要： The invention encompasses methods of maintaining desired recombinant genes in a genetic population of cells expressing the desired gene. The methods utilize microbial cells that have an inactivating mutation in a native essential gene encoding an enzyme which catalyzes a step in the biosynthesis of diaminopimelic acid (DAP). The cells also have an extrachromosomal vector that includes the desired gene and which is capable of homologous recombination with a chromosome of the microorganism. The vector also has a recombinant complementing gene encoding a functional replacement of the native essential gene. The cells of the invention are particularly useful for components of vaccines, including DNA vaccines.
摘要翻译：本发明包括在表达所需基因的细胞的遗传群体中维持所需重组基因的方法。该方法利用编码催化二氨基庚二酸（DAP）生物合成步骤的酶的天然必需基因中具有失活突变的微生物细胞。细胞还具有包含所需基因并且能够与微生物的染色体同源重组的染色体外载体。载体还具有编码天然必需基因功能性替代的重组补体基因。本发明的细胞特别可用于疫苗的组分，包括DNA疫苗。

14. 发明授权

US06610529B1 Recombinant bacterial system with environmentally limited viability 失效
标题翻译：具有环境有限生命力的重组细菌系统
公开(公告)号：US06610529B1
公开(公告)日：2003-08-26
申请号：US08761769
申请日：1996-12-06
申请人： Roy Curtiss, III , Steven A. Tinge
发明人： Roy Curtiss, III , Steven A. Tinge
IPC分类号： C12N121
CPC分类号： C12N15/64 , C12N15/70 , C12N15/74
摘要： Disclosed is an Environmentally Limited Viability System (ELVS) for microorganisms based on differences between permissive and non-permissive environments. Viability of the microorganisms are limited to a permissive environment by specifically expressing one or more essential genes only in the permissive environment, and/or expressing one or more lethal genes only in the non-permissive environment. Temporary viability in a non-permissive environment can be achieved by temporarily expressing one or more essential genes in a non-permissive environment, and/or temporarily delaying expression of one or more lethal genes in the non-permissive environment. Environmentally Limited Viability Systems are also disclosed involving coordinate expression of a combination of essential genes and lethal genes. Microorganisms containing an Environmentally Limited Viability System are useful for release into permissive and non-permissive environments. Temperature regulated Environmentally Limited Viability Systems and delayed death Environmentally Limited Viability Systems are particularly suited for delivery of expression products, such as antigens, using recombinant avirulent Salmonella by limiting their growth to the warmer environment inside the host, or by allowing growth for only a limited time in the host.
摘要翻译：公开了基于许可和非允许环境之间的微生物的环境有限的生存力系统（ELVS）。通过仅在许可环境中特异性表达一个或多个必需基因，和/或仅在非允许环境中表达一个或多个致死基因，将微生物的活力限制为允许的环境。通过在非允许环境中临时表达一种或多种必需基因，和/或在非允许环境中暂时延缓一种或多种致死基因的表达，可以实现非允许环境中的临时活力。还公开了环境有限的生命力系统，涉及协调基本基因和致死基因组合的表达。含有环境有限生命力系统的微生物对于释放到许可和不允许的环境中是有用的。温度调节环境有限的生存能力系统和延迟死亡环境有限的生存能力系统特别适合于通过将其生长限制在宿主内较温暖的环境中，或通过允许生长仅限于有限的方式，使用重组无毒力沙门氏菌来递送表达产物，如抗原时间在主机。

15. 发明授权

US5468485A Avirulent microbes and uses therefor 失效
标题翻译：无毒微生物及其用途
公开(公告)号：US5468485A
公开(公告)日：1995-11-21
申请号：US20259
申请日：1993-02-18
申请人： Roy Curtiss, III
发明人： Roy Curtiss, III
IPC分类号： C12N15/00 , C12N15/74 , A61K39/00 , A61K39/02 , C12N1/21
CPC分类号： A61K39/099 , A61K39/0258 , A61K39/0275 , C12N15/00 , C12N15/74 , C12R1/42 , A61K2039/523 , A61K2039/552
摘要： This invention provides a vaccine for the immunization of a vertebrate or invertebrate comprising an avirulent derivative of S. choleraesuis. The derivatives being substantially incapable of producing functional adenylate cyclase and/or cyclic AMP receptor protein. The invention also provides a vaccine for the immunization of a vertebrate and invertebrate comprising a virulent derivative of a pathogenic microbe said derivative being substantially incapable of producing functional adenylate cyclase and/or cyclic AMP receptor protein while being capable of expressing a recombinant gene derived from a pathogen of said vertebrate to produce an antigen capable of inducing an immune response in said vertebrate against said pathogen.
摘要翻译：本发明提供了用于免疫脊椎动物或无脊椎动物的疫苗，其包含霍乱病毒的无毒性衍生物。该衍生物基本上不能产生功能性腺苷酸环化酶和/或环AMP受体蛋白。本发明还提供了用于免疫脊椎动物和无脊椎动物的疫苗，其包含病原微生物的有毒衍生物，所述衍生物基本上不能产生功能性腺苷酸环化酶和/或环AMP受体蛋白质，同时能够表达源自所述脊椎动物的病原体产生能够在所述脊椎动物中针对所述病原体诱导免疫应答的抗原。

16. 发明授权

US5387744A Avirulent microbes and uses therefor: Salmonella typhi 失效
标题翻译：无毒性微生物及其用途：伤寒沙门氏菌
公开(公告)号：US5387744A
公开(公告)日：1995-02-07
申请号：US88394
申请日：1993-07-07
申请人： Roy Curtiss, III , Sandra M. Kelly
发明人： Roy Curtiss, III , Sandra M. Kelly
IPC分类号： A61K39/04 , C07K14/255 , C07K14/315 , C07K14/35 , C12N1/21 , C12N9/02 , C12N15/00 , C12N15/01 , C12N15/68 , A61K39/112
CPC分类号： A61K39/099 , A61K39/0275 , A61K39/04 , C07K14/255 , C07K14/315 , C07K14/35 , C12N15/00 , C12N15/01 , C12N15/68 , C12N9/0008 , C12R1/42 , C12Y102/01011 , A61K2039/522 , A61K2039/523 , A61K2039/552 , Y10S435/879
摘要： This invention provides immunogenic compositions for the immunization of a vertebrate or invertebrate comprising an avirulent derivative of S. typhi. The derivatives having a mutation of the cya and/or crp and/or cdt genes. The invention also provides immunogenic compositions for the immunization of a vertebrate and invertebrate comprising an avirulent derivative of the above type which is capable of expressing a recombinant gene derived from a pathogen of said vertebrate or invertebrate individual to produce an antigen capable of inducing an immune response against said pathogen. Other embodiments of the invention include methods of preparing immunogenic compositions from these strains, and strains useful in the preparation of the immunogenic compositions, as well as methods of stimulating the immune system to respond to an immunogenic antigen of S. typhi by administration of the immunogenic composition.
摘要翻译：本发明提供了用于免疫含脊椎动物或无脊椎动物的免疫原性组合物，其包含伤寒沙利氏菌的无毒性衍生物。具有cya和/或crp和/或cdt基因突变的衍生物。本发明还提供用于免疫脊椎动物和无脊椎动物的免疫原性组合物，其包含上述类型的无毒力衍生物，其能够表达源自所述脊椎动物或无脊椎动物个体的病原体的重组基因以产生能够诱导免疫应答的抗原针对所述病原体。本发明的其它实施方案包括从这些菌株制备免疫原性组合物的方法，以及可用于制备免疫原性组合物的菌株，以及通过施用免疫原性刺激免疫系统对伤寒沙门氏菌的免疫原性抗原作出反应的方法组成。

17. 发明授权

US4968619A Modified microorganisms and method of preparing and using same 失效
标题翻译：改性微生物及其制备及使用方法
公开(公告)号：US4968619A
公开(公告)日：1990-11-06
申请号：US513237
申请日：1983-10-17
申请人： Roy Curtiss, III
发明人： Roy Curtiss, III
IPC分类号： C12N1/21 , C12N15/00
CPC分类号： C12N15/00 , Y10S435/849
摘要： Microorganisms have been developed which may be characterized as possessing substantially all of the following qualities or capabilities:(a) capable of having foreign genetic information introduced thereinto and recovered therefrom along with its expression with production of useful gene products;(b) the microorganism being dependent for growth and survival upon defined conditions;(c) the microorganism being incapable of establishment or growth or colonization and/or survival under conditions or in ecological niches that are considered to be natural and/or undesirable for said microorganism;(d) the microorganism being capable of causing genetic information incorporated therein to undergo degradation under conditions or ecological niches that are considered to be natural and/or undesirable for said microorganism;(e) the microorganism being capable of permitting cloning vectors incorporated therein to be dependent for their replication, maintenance and/or function on said microorganism;(f) the microorganism being substantially incapable of transmitting cloning vectors or recombinant DNA molecules incorporated therein to other organisms under conditions or ecological niches that are considered to be natural and/or undesirable for said microorganism;(g) the microorganism being capable of being monitored by suitable means and/or techniques without substantial alteration of said microorganism; and(h) the microorganism being susceptible of substantially minimal contamination with other organisms when recombinant DNA molecules are incorporated therein and being substantially incapable of contaminating other organisms when incorporated therein or consumed thereby when recombinant DNA molecules are incorporated in said microorganism.
摘要翻译：已经开发了微生物，其特征在于具有基本上所有以下特征或能力：（a）能够将外源遗传信息与其表达一起引入并从其中回收并产生有用的基因产物; （b）微生物在规定的条件下依赖于生长和存活; （c）微生物在被认为对所述微生物是天然的和/或不期望的条件下或在生态龛内不能建立或生长或定殖和/或存活; （d）能够引入其中遗传信息的微生物在被认为是天然的和/或不希望的所述微生物的条件或生态位下进行降解; （e）能够允许并入其中的克隆载体依赖于其对所述微生物的复制，维持和/或功能的微生物; （f）微生物在被认为对所述微生物是天然的和/或不期望的条件或生态龛处基本上不能将掺入其中的克隆载体或重组DNA分子传输到其他生物体; （g）微生物能够通过适当的手段和/或技术进行监测，而不显着改变所述微生物; 和（h）当重组DNA分子并入其中时，微生物易于受到其他生物体的基本上最小的污染，并且当重组DNA分子并入所述微生物中时基本上不能将其掺入或消耗其它生物体而被污染。

18. 发明授权

US09598697B2 Recombinant bacterium to decrease tumor growth 有权
公开(公告)号：US09598697B2
公开(公告)日：2017-03-21
申请号：US13700591
申请日：2011-05-31
申请人： Roy Curtiss, III , Wei Kong
发明人： Roy Curtiss, III , Wei Kong
IPC分类号： A01N63/00 , C12N1/20 , C12N15/74 , C12R1/42 , A61K35/74 , C12N1/36
CPC分类号： C12N15/74 , A61K35/74 , C12N1/36 , C12R1/42
摘要： A recombinant bacterium capable of reducing tumor growth is provided, wherein said recombinant bacterium is capable of: a. increased expression of a nucleic acid encoding a chemoreceptor that directs chemotaxis towards tumors, b. accumulation in a quiescent tumor, c. hyper-invasion of a tumor, d. reduced fitness in normal tissue, e. enhanced stimulation of the host innate immune responses, f. delivering a tumor specific DNA vaccine vector to a tumor cell, and g. increased bacterium-induced host programmed cell death.

19. 发明授权

US09297015B2 Regulated expression of antigen and/or regulated attentuation to enhance vaccine immunogenicity and/or safety 有权
公开(公告)号：US09297015B2
公开(公告)日：2016-03-29
申请号：US13789665
申请日：2013-03-07
申请人： Roy Curtiss, III , Shifeng Wang , Soo-Young Wanda , Wei Kong
发明人： Roy Curtiss, III , Shifeng Wang , Soo-Young Wanda , Wei Kong
IPC分类号： A61K35/74 , C12N15/74 , C12N1/36 , A61K39/00
CPC分类号： C12N15/74 , A61K35/74 , A61K39/00 , A61K2035/11 , A61K2039/522 , A61K2039/523 , C12N1/36
摘要： The invention relates to compositions and methods for making and using recombinant bacteria that are capable of regulated attenuation and/or regulated expression of one or more antigens of interest.

20. 发明授权

US09255283B2 Compositions and methods for bacterial lysis and neutral lipid production 有权
标题翻译：细菌裂解和中性脂质生成的组成和方法
公开(公告)号：US09255283B2
公开(公告)日：2016-02-09
申请号：US13805733
申请日：2011-07-01
申请人： Roy Curtiss, III , Xinyao Liu
发明人： Roy Curtiss, III , Xinyao Liu
IPC分类号： C12P7/64 , C07K14/195 , C12N9/18 , C12N9/20 , C12N9/36
CPC分类号： C12P7/6463 , C07K14/195 , C12N9/18 , C12N9/20 , C12N9/2462
摘要： The present invention is directed to a cyanobacterium that produces neutral lipids or alkanes. Such neutral lipids or alkanes may be used for biofuel production.
摘要翻译：本发明涉及产生中性脂质或烷烃的蓝细菌。这种中性脂质或烷烃可用于生产生物燃料。

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