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41. 发明授权

US09155788B2 Application of mRNA for use as a therapeutic against tumour diseases 有权
标题翻译： mRNA用于治疗肿瘤疾病的应用
公开(公告)号：US09155788B2
公开(公告)日：2015-10-13
申请号：US14325850
申请日：2014-07-08
申请人： CUREVAC GMBH
发明人： Ingmar Hoerr , Florian Von Der Mulbe , Steve Pascolo
IPC分类号： A61K39/00 , A61K38/19
CPC分类号： A61K39/0011 , A61K9/0021 , A61K38/193 , A61K48/00 , A61K2039/53 , A61K2039/54 , A61K2039/55522 , A61K2039/572 , A61K2039/70 , A61K2300/00
摘要： The present invention relates to a pharmaceutical composition comprising at least one mRNA comprising at least one coding region for at least one antigen from a tumor, in combination with an aqueous solvent and preferably a cytokine, e.g. GM-CSF, and a process for the preparation of the pharmaceutical composition. The pharmaceutical composition according to the invention is used in particular for therapy and/or prophylaxis against cancer.
摘要翻译：本发明涉及一种药物组合物，其包含至少一种mRNA，其包含至少一个来自肿瘤的至少一种抗原的编码区，与水性溶剂，优选细胞因子（例如细胞因子）组合。 GM-CSF，以及制备药物组合物的方法。本发明的药物组合物特别用于治疗和/或预防癌症。

42. 发明申请

US20150057340A1 NUCLEIC ACID COMPRISING OR CODING FOR A HISTONE STEM-LOOP AND A POLY(A) SEQUENCE OR A POLYADENYLATION SIGNAL FOR INCREASING THE EXPRESSION OF AN ENCODED THERAPEUTIC PROTEIN 有权
标题翻译：用于组蛋白干扰素的核酸包封或编码，以及用于增加编码的治疗蛋白质的表达的聚（A）序列或聚乙烯化信号
公开(公告)号：US20150057340A1
公开(公告)日：2015-02-26
申请号：US14378606
申请日：2013-02-15
申请人： CureVac GmbH
发明人： Andreas Thess , Thomas Schlake , Jochen Probst
IPC分类号： C12N15/85
CPC分类号： A61K48/0066 , A61K39/00 , A61K48/00 , C07K14/505 , C07K16/32 , C07K2317/14 , C07K2317/24 , C12N15/63 , C12N15/67 , C12N15/85 , C12N2830/50 , C12N2840/105
摘要： The present invention relates to a nucleic acid sequence, comprising or coding for a coding region, encoding at least one peptide or protein comprising a therapeutic protein or a fragment, variant or derivative thereof, at least one histone stem-loop and a poly(A) sequence or a polyadenylation signal. Furthermore the present invention provides the use of the nucleic acid for increasing the expression of said encoded peptide or protein, particularly for the use in gene therapy. It also discloses its use for the preparation of a pharmaceutical composition, e.g. for use in gene therapy, particularly in the treatment of diseases which are in need of a treatment with a therapeutic peptide or protein, preferably as defined herein. The present invention further describes a method for increasing the expression of a peptide or protein comprising a therapeutic protein or a fragment, variant or derivative thereof, using the nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal.
摘要翻译：本发明涉及包含或编码编码区的核酸序列，其编码至少一种包含治疗性蛋白质或其片段，变体或衍生物的肽或蛋白质，至少一种组蛋白茎环和聚（A ）序列或聚腺苷酸化信号。此外，本发明提供了用于增加所述编码的肽或蛋白质的表达的核酸的用途，特别是用于基因治疗。它还公开了其用于制备药物组合物的用途，例如用于基因治疗，特别是用于治疗需要用治疗性肽或蛋白质治疗的疾病，优选如本文所定义。本发明还描述了使用包含或编码组蛋白茎环和聚（A）序列的核酸或增加包含治疗性蛋白或其片段，变体或衍生物的肽或蛋白质的表达的方法，多聚腺苷酸化信号。

43. 发明申请

US20150050302A1 ARTIFICIAL NUCLEIC ACID MOLECULES COMPRISING A 5'TOP UTR 审中-公开
标题翻译：包含5'TOP UTR的人造核酸分子
公开(公告)号：US20150050302A1
公开(公告)日：2015-02-19
申请号：US14388224
申请日：2013-03-27
申请人： CureVac GmbH
发明人： Andreas Thess
IPC分类号： A61K48/00 , A61K39/00
CPC分类号： A61K48/0066 , A61K38/00 , A61K39/00 , C12N15/67 , C12N15/85 , C12N2830/50 , C12N2830/85 , C12N2840/105
摘要： The invention relates to an artificial nucleic acid molecule comprising at least one 5′UTR element which is derived from a TOP gene, at least one open reading frame and optionally at least one 3′UTR element comprising a nucleic acid sequence which is preferably derived from the 3′UTR of a gene providing a stable mRNA, such as an albumin gene, or from a variant of the 3′UTR of a gene providing a stable mRNA. The invention further relates to the use of such an artificial nucleic acid molecule in gene therapy and/or genetic vaccination.
摘要翻译：本发明涉及包含至少一个5'UTR元件的人造核酸分子，其衍生自TOP基因，至少一个开放阅读框和任选的至少一个3'UTR元件，其包含优选衍生自提供稳定mRNA的基因的3'UTR，例如白蛋白基因，或提供稳定mRNA的基因的3'UTR的变体。本发明还涉及这种人工核酸分子在基因治疗和/或基因疫苗接种中的用途。

44. 发明授权

US09669089B2 Nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal for increasing the expression of an encoded pathogenic antigen 有权
公开(公告)号：US09669089B2
公开(公告)日：2017-06-06
申请号：US14378538
申请日：2013-02-15
申请人： CureVac GmbH
发明人： Andreas Thess , Thomas Schlake , Jochen Probst
IPC分类号： A61K48/00 , A61K38/00 , A61K39/145 , A61K39/00 , C12N15/67 , C12N15/63 , A61K39/12 , C12N7/00
CPC分类号： A61K39/145 , A61K39/00 , A61K39/12 , A61K2039/53 , A61K2039/64 , C12N7/00 , C12N15/63 , C12N15/67 , C12N2760/16134 , C12N2830/50 , Y02A50/386 , Y02A50/388 , Y02A50/403 , Y02A50/414 , Y02A50/416 , Y02A50/464 , Y02A50/466 , Y02A50/476 , Y02A50/487 , Y02A50/489 , Y02A50/491 , Y02A50/492
摘要： The present invention relates to a nucleic acid sequence, comprising or coding for a coding region, encoding at least one peptide or protein comprising a pathogenic antigen or a fragment, variant or derivative thereof, at least one histone stem-loop and a poly(A) sequence or a polyadenylation signal. Furthermore the present invention provides the use of the nucleic acid for increasing the expression of said encoded peptide or protein. It also discloses its use for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the treatment of infectious diseases. The present invention further describes a method for increasing the expression of a peptide or protein comprising a pathogenic antigen or a fragment, variant or derivative thereof, using the nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal.

45. 发明授权

US09447431B2 Nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal for increasing the expression of an encoded therapeutic protein 有权
标题翻译：包含或编码组蛋白茎环的核酸和用于增加编码的治疗性蛋白质的表达的聚（A）序列或多聚腺苷酸化信号
公开(公告)号：US09447431B2
公开(公告)日：2016-09-20
申请号：US14378606
申请日：2013-02-15
申请人： CureVac GmbH
发明人： Andreas Thess , Thomas Schlake , Jochen Probst
IPC分类号： C12N15/67 , C12N15/63 , C12N15/85 , A61K48/00 , C07H21/00 , C12N15/09 , C12N15/74 , C12N15/79 , C12P21/02
CPC分类号： A61K48/0066 , A61K39/00 , A61K48/00 , C07K14/505 , C07K16/32 , C07K2317/14 , C07K2317/24 , C12N15/63 , C12N15/67 , C12N15/85 , C12N2830/50 , C12N2840/105
摘要： The present invention relates to a nucleic acid sequence, comprising or coding for a coding region, encoding at least one peptide or protein comprising a therapeutic protein or a fragment, variant or derivative thereof, at least one histone stem-loop and a poly(A) sequence or a polyadenylation signal. Furthermore the present invention provides the use of the nucleic acid for increasing the expression of said encoded peptide or protein, particularly for the use in gene therapy. It also discloses its use for the preparation of a pharmaceutical composition, e.g. for use in gene therapy, particularly in the treatment of diseases which are in need of a treatment with a therapeutic peptide or protein, preferably as defined herein. The present invention further describes a method for increasing the expression of a peptide or protein comprising a therapeutic protein or a fragment, variant or derivative thereof, using the nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal.
摘要翻译：本发明涉及包含或编码编码区的核酸序列，其编码至少一种包含治疗性蛋白质或其片段，变体或衍生物的肽或蛋白质，至少一种组蛋白茎环和聚（A ）序列或聚腺苷酸化信号。此外，本发明提供了用于增加所述编码的肽或蛋白质的表达的核酸的用途，特别是用于基因治疗。它还公开了其用于制备药物组合物的用途。用于基因治疗，特别是用于治疗需要用治疗性肽或蛋白质治疗的疾病，优选如本文所定义。本发明还描述了使用包含或编码组蛋白茎环和聚（A）序列的核酸或增加包含治疗性蛋白或其片段，变体或衍生物的肽或蛋白质的表达的方法，多聚腺苷酸化信号。

46. 发明申请

US20160082092A1 APPLICATION OF mRNA FOR USE AS A THERAPEUTIC AGAINST TUMOUR DISEASES 审中-公开
公开(公告)号：US20160082092A1
公开(公告)日：2016-03-24
申请号：US14840305
申请日：2015-08-31
申请人： CureVac GmbH
发明人： Ingmar HOERR , Florian VON DER MÜLBE , Steve PASCOLO
IPC分类号： A61K39/00 , A61K38/19
CPC分类号： A61K39/0011 , A61K9/0021 , A61K38/193 , A61K48/00 , A61K2039/53 , A61K2039/54 , A61K2039/55522 , A61K2039/572 , A61K2039/70 , A61K2300/00
摘要： The present invention relates to a pharmaceutical composition comprising at least one mRNA comprising at least one coding region for at least one antigen from a tumour, in combination with an aqueous solvent and preferably a cytokine, e.g. GM-CSF, and a process for the preparation of the pharmaceutical composition. The pharmaceutical composition according to the invention is used in particular for therapy and/or prophylaxis against cancer.

47. 发明申请

US20150320847A1 NUCLEIC ACID COMPRISING OR CODING FOR A HISTONE STEM-LOOP AND A POLY(A) SEQUENCE OR A POLYADENYLATION SIGNAL FOR INCREASING THE EXPRESSION OF AN ENCODED TUMOUR ANTIGEN 有权
标题翻译：包含或编码HISTONE STEM-LOOP和POLY（A）序列或用于增加编码的肿瘤抗原表达的聚苯乙烯信号的核酸
公开(公告)号：US20150320847A1
公开(公告)日：2015-11-12
申请号：US14378572
申请日：2013-02-15
申请人： CureVac GmbH
发明人： Andreas THESS , Thomas SCHLAKE , Jochen PROBST
IPC分类号： A61K39/00 , C12N15/67 , C07K14/47
CPC分类号： A61K39/0011 , A61K38/00 , A61K2039/53 , A61K2039/64 , C07K14/47 , C07K14/4703 , C07K14/4748 , C12N15/63 , C12N15/67 , C12N2830/50
摘要： The present invention relates to a nucleic acid sequence, comprising or coding for a coding region, encoding at least one peptide or protein comprising a tumour antigen or a fragment, variant or derivative thereof, at least one histone stem-loop and a poly(A) sequence or a polyadenylation signal. Furthermore the present invention provides the use of the nucleic acid for increasing the expression of said encoded peptide or protein. It also discloses its use for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the treatment of cancer or tumour diseases. The present invention further describes a method for increasing the expression of a peptide or protein comprising a tumour antigen or a fragment, variant or derivative thereof, using the nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal.
摘要翻译：本发明涉及包含或编码编码区的核酸序列，其编码至少一种包含肿瘤抗原或其片段，变体或衍生物的肽或蛋白质，至少一种组蛋白茎环和聚（A ）序列或聚腺苷酸化信号。此外，本发明提供了用于增加所述编码的肽或蛋白质的表达的核酸的用途。它还公开了其用于制备药物组合物，特别是疫苗的用途。用于治疗癌症或肿瘤疾病。本发明还描述了使用包含或编码组蛋白茎环和聚（A）序列的核酸或增加包含肿瘤抗原或其片段，变体或衍生物的肽或蛋白质的表达的方法，多聚腺苷酸化信号。

48. 发明申请

US20150141498A1 MANNOSE-CONTAINING SOLUTION FOR LYOPHILIZATION, TRANSFECTION AND/OR INJECTION OF NUCLEIC ACIDS 有权
标题翻译：包含核酸的柠檬酸化，转运和/或注射的含有含水的方法
公开(公告)号：US20150141498A1
公开(公告)日：2015-05-21
申请号：US14492334
申请日：2014-09-22
申请人： CureVac GmbH
发明人： Thorsten MUTZKE
IPC分类号： A61K31/7088 , A61K48/00 , A61K39/00 , A61K47/26 , A61K47/12
CPC分类号： A61K31/7088 , A61K39/0011 , A61K47/12 , A61K47/26 , A61K48/00 , A61K2039/53 , C12N15/87
摘要： The present invention is directed to (the use of) a solution containing at least one nucleic acid (sequence) and free mannose for lyophilization, transfection and/or injection, particularly of RNA and mRNA. The inventive solution exhibits a positive effect on stabilization of the nucleic acid (sequence) during lyophilization and storage but also leads to a considerable increase of the transfection efficiency of a nucleic acid. It thus also increases in vivo expression of a protein encoded by such a nucleic acid upon increased transfection rate. The present invention is furthermore directed to a method of lyophilization using the mannose-containing solution, to pharmaceutical compositions, vaccines, kits, first and second medical uses applying such a mannose-containing solution and/or a nucleic acid (sequence) lyophilized or resuspended with such a solution.
摘要翻译：本发明涉及包含至少一种核酸（序列）和游离甘露糖的溶液（用于）冻干，转染和/或注射，特别是RNA和mRNA的溶液（的用途）。本发明溶液对冷冻干燥和储存期间核酸（序列）的稳定性具有积极作用，但也导致核酸转染效率的显着增加。因此，在增加的转染率时，它也增加了由这种核酸编码的蛋白质的体内表达。本发明还涉及使用含甘露糖的溶液，药物组合物，疫苗，试剂盒，使用这种含甘露糖的溶液和/或冻干或重新悬浮的核酸（序列）的第一和第二医疗用途的冻干方法。用这样的解决方案。

49. 发明申请

US20150118264A1 PHARMACEUTICAL COMPOSITION COMPRISING A POLYMERIC CARRIER CARGO COMPLEX AND AT LEAST ONE PROTEIN OR PEPTIDE ANTIGEN 审中-公开
标题翻译：包含聚合物载体复合物和至少一种蛋白质或肽抗原的药物组合物
公开(公告)号：US20150118264A1
公开(公告)日：2015-04-30
申请号：US14375215
申请日：2013-01-31
申请人： CureVac GmbH
发明人： Patrick Baumhof , Thomas Kramps , Söhnke Voss , Karl-Josef Kallen , Mariola Fotin-Mleczek
IPC分类号： A61K39/39 , A61K48/00 , A61K39/35 , A61K39/00 , C12N7/00 , A61K39/145 , A61K39/29 , A61K39/12 , A61K47/48 , A61K39/205
CPC分类号： A61K39/39 , A61K39/0011 , A61K39/12 , A61K39/145 , A61K39/205 , A61K39/29 , A61K39/35 , A61K47/645 , A61K47/646 , A61K48/0041 , A61K2039/5252 , A61K2039/53 , A61K2039/55511 , A61K2039/55516 , A61K2039/55561 , A61K2039/572 , A61K2039/575 , A61K2039/6093 , C12N7/00 , C12N2710/20034 , C12N2710/20071 , C12N2730/10134 , C12N2730/10171 , C12N2760/16134 , C12N2760/16171 , C12N2760/20134 , C12N2760/20171 , Y02A50/416
摘要： The present invention is directed to a pharmaceutical composition including (e.g. for use as an adjuvant) a polymeric carrier cargo complex, comprising as a carrier a polymeric carrier formed by disulfide-crosslinked cationic components; and as a cargo at least one nucleic acid molecule, and at least one antigen that is selected from an antigen from a pathogen associated with infectious disease; an antigen associated with allergy or allergic disease; an antigen associated with autoimmune disease; or an antigen associated with a cancer or tumour disease, or in each case a fragment, variant and/or derivative of said antigen. The pharmaceutical composition allows for efficient induction of an adaptive immune response directed against said antigen. The present invention furthermore provides kits, as well as the use of the pharmaceutical composition or the kit as a vaccine, particularly in the treatment of infectious diseases, allergies, autoimmune diseases and tumour or cancer diseases.
摘要翻译：本发明涉及包含（例如用作佐剂）聚合物载体货物复合物的药物组合物，其包含作为载体的由二硫化物交联的阳离子组分形成的聚合物载体; 以及作为货物至少一种核酸分子和至少一种选自与感染性疾病相关的病原体的抗原的抗原; 与过敏或过敏性疾病相关的抗原; 与自身免疫性疾病相关的抗原; 或与癌症或肿瘤疾病相关的抗原，或在每种情况下都是所述抗原的片段，变体和/或衍生物。药物组合物允许有效诱导针对所述抗原的适应性免疫应答。本发明还提供试剂盒，以及药物组合物或试剂盒作为疫苗的用途，特别是用于治疗感染性疾病，过敏反应，自身免疫性疾病和肿瘤或癌症疾病。

50. 发明申请

US20150104476A1 PHARMACEUTICAL COMPOSITION CONTAINING A STABILISED mRNA OPTIMISED FOR TRANSLATION IN ITS CODING REGIONS 审中-公开
标题翻译：含有稳定化mRNA的药物组合物在其编码区域中进行翻译优化
公开(公告)号：US20150104476A1
公开(公告)日：2015-04-16
申请号：US14487425
申请日：2014-09-16
申请人： CureVac GmbH
发明人： Florian VON DER MÜLBE , Ingmar HOERR , Steve PASCOLO
IPC分类号： C12N15/11 , C07K14/005 , A61K39/108 , A61K39/00 , C12N7/00 , C07K14/245 , A61K39/145
CPC分类号： A61K48/005 , A61K38/1735 , A61K38/1816 , A61K38/19 , A61K38/193 , A61K38/28 , A61K39/00 , A61K39/0011 , A61K39/0258 , A61K39/12 , A61K39/145 , A61K39/21 , A61K47/542 , A61K47/6455 , A61K48/00 , A61K48/0066 , A61K48/0075 , A61K48/0083 , A61K2039/53 , C07K14/005 , C07K14/245 , C07K14/4727 , C07K14/4748 , C12N7/00 , C12N15/11 , C12N15/67 , C12N2310/334 , C12N2310/336 , C12N2740/16022 , C12N2740/16034 , C12N2760/14122 , C12N2760/14134 , C12N2760/16022 , C12N2760/16034 , C12N2760/16071 , C12N2770/24122 , C12N2770/24134 , G16B20/00 , G16B30/00 , Y02A50/386 , Y02A50/388 , Y02A50/416 , Y02A50/464 , A61K2300/00
摘要： The present invention relates to a pharmaceutical composition comprising a modified mRNA that is stabilised by sequence modifications and optimised for translation. The pharmaceutical composition according to the invention is particularly well suited for use as an inoculating agent, as well as a therapeutic agent for tissue regeneration. In addition, a process is described for determining sequence modifications that promote stabilisation and translational efficiency of modified mRNA of the invention.
摘要翻译：本发明涉及一种药物组合物，其包含通过序列修饰稳定并优化翻译的经修饰的mRNA。根据本发明的药物组合物特别适合用作接种剂，以及用于组织再生的治疗剂。此外，描述了用于确定促进本发明的修饰的mRNA的稳定性和翻译效率的序列修饰的方法。

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