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1. 发明专利

CA3017285A1 TRANS-REPLICATING RNA 未知
公开(公告)号：CA3017285A1
公开(公告)日：2017-09-28
申请号：CA3017285
申请日：2017-03-13
申请人： BIONTECH RNA PHARMACEUTICALS GMBH , TRON TRANSLATIONALE ONKOLOGIE AN DER UNIV DER JOHANNES GUTENBERG UNIV MAINZ GEMEINNUTZIGE GMBH
发明人： BEISSERT TIM , SAHIN UGUR , PERKOVIC MARIO
IPC分类号： C12N15/86 , A61K48/00 , C12N5/10 , C12N15/40
摘要： The present invention generally relates to systems and methods suitable for high-level protein production. While one or more elements of the present invention are derived from an alphavirus, the present invention does not require propagation of virus particles. In particular, a system comprising two separate RNA molecules is foreseen, each comprising a nucleotide sequence derived from an alphavirus: one RNA molecule comprises a RNA construct for expressing alphavirus replicase, and one RNA molecule comprises a RNA re pi icon that can be replicated by the replicase in trans. The RNA construct for expressing alphavirus replicase comprises a 5'-cap. It was surprisingly found that the 5'-cap is suitable for efficiently driving expression of a transgene from the replicon in trans. The system of the present invention enables expression of a protein of interest in a cell or organism, but is not associated with undesired virus-particle formation. Therefore, the present invention is suitable for efficiently and safely producing a protein of interest, e.g. a therapeutic protein or an antigenic protein, such as a vaccine, in a target organism. Respective methods of protein production in vitro and in vivo as well as medical uses are provided herein. The present invention also provides DNA encoding the RNA molecules of the invention, and cells comprising the RNA molecules of the invention.

2. 发明专利

CA3017272A1 RNA REPLICON FOR VERSATILE AND EFFICIENT GENE EXPRESSION 未知
公开(公告)号：CA3017272A1
公开(公告)日：2017-09-28
申请号：CA3017272
申请日：2017-03-13
申请人： BIONTECH RNA PHARMACEUTICALS GMBH , TRON TRANSLATIONALE ONKOLOGIE AN DER UNIV DER JOHANNES GUTENBERG UNIV MAINZ GEMEINNUTZIGE GMBH
发明人： BEISSERT TIM , SAHIN UGUR , PERKOVIC MARIO
IPC分类号： C12N15/86 , C12N5/10 , C12N15/85
摘要： The present invention embraces a RNA replicon that can be replicated by a replicase of alphavirus origin. The RNA replicon comprises sequence elements required for replication by the replicase, but these sequence elements do not encode any protein or fragment thereof, such as an alphavirus non-structural protein or fragment thereof. Thus, in the RNA replicon according to the invention, sequence elements required for replication by the replicase and protein-coding region(s) are uncoupled. According to the present invention the uncoupling is achieved by the removal of at least one initiation codon compared to a native alphavirus genomic RNA. In particular, the RNA replicon comprises a 5' replication recognition sequence, wherein the 5' replication recognition sequence is characterized in that it comprises the removal of at least one initiation codon compared to a native alphavirus 5' replication recognition sequence. The replicase of alphavirus origin may be encoded by an open reading frame on the RNA replicon or on a separate RNA molecule. The present invention enables efficient and safe expression of a protein of interest in a cell or organism, but is not associated with undesired production of fragments of alphavirus non-structural protein. Methods of protein production in vitro and in vivo, as well as medical uses, are provided herein.

3. 发明专利

MD3433368T2 Trans-replicarea ARN 未知
公开(公告)号：MD3433368T2
公开(公告)日：2021-12-31
申请号：MDE20190126
申请日：2017-03-13
申请人： BIONTECH SE , TRON TRANSLATIONALE ONKOLOGIE AN DER UNIV DER JOHANNES GUTENBERG UNIV MAINZ GEMEINNUTZIGE GMBH
发明人： BEISSERT TIM , SAHIN UGUR , PERKOVIC MARIO
IPC分类号： C12N15/86 , A61K48/00 , C12N5/10 , C12N15/40
摘要： Prezenta invenţie se referă în general la sisteme şi metode adecvate pentru producerea de proteine de nivel înalt. În timp ce unul sau mai multe elemente ale prezentei invenţii sunt derivate dintr-un alfavirus, prezenta invenţie nu necesită propagarea particulelor de virus. În special, este prevăzut un sistem care cuprinde două molecule de ARN separate, fiecare cuprinzând o secvenţă de nucleotide derivată dintr-un alfavirus: o moleculă de ARN cuprinde un construct de ARN pentru exprimarea replicazei alfavirusului şi o moleculă de ARN cuprinde o pictogramă ARN re pi care poate fi replicată prin replicaza în trans. Construcţia ARN pentru exprimarea replicazei alfavirusului cuprinde un capac 5'. S-a descoperit în mod surprinzător că capacul 5' este adecvat pentru a conduce eficient expresia unei transgene din replicon în trans. Sistemul prezentei invenţii permite exprimarea unei proteine de interes într-o celulă sau organism, dar nu este asociat cu formarea nedorită de particule de virus. Prin urmare, prezenta invenţie este adecvată pentru producerea eficientăşi sigură a unei proteine de interes, de ex. o proteină terapeutică sau o proteină antigenică, cum ar fi un vaccin, într-un organism ţintă. Metodele respective de producere a proteinelor in vitro şi in vivo, precum şi utilizări medicale sunt furnizate aici. Prezenta invenţie furnizează de asemenea ADN care codifică moleculele de ARN ale invenţiei şi celule care cuprind molecule de ARN ale invenţiei.

4. 发明专利

RU2752580C2 ТРАНС-РЕПЛИЦИРУЮЩАЯ РНК 未知
公开(公告)号：RU2752580C2
公开(公告)日：2021-07-29
申请号：RU2018131783
申请日：2017-03-13
申请人： BIONTECH RNA PHARMACEUTICALS GMBH
发明人： BEISSERT TIM , SAHIN UGUR , PERKOVIC MARIO
IPC分类号： C12N15/86 , A61K48/00 , C12N5/10 , C12N15/40
摘要： Изобретениеотноситсяк областибиотехнологии. Описанагруппаизобретений, включающаясистемудляполучениябелка, фармацевтическуюкомпозициюдляэкспрессииальфавируснойрепликазыи/илирепликона, способполучениябелкав клетке, эукариотическуюклетку-хозяиндляполучениябелкаи способполучениябелкау субъекта. ВодномизвариантовреализациисистемасодержитконструкциюРНКдляэкспрессииальфавируснойрепликазыи РНК-репликон, которыйможетбытьреплицированрепликазойin trans, причемконструкцияРНКсодержит 5' UTR, открытуюрамкусчитывания, кодирующуюрепликазу, и 3' UTR, гдеконструкцияРНКсодержит 5’-кэпдлятрансляциирепликазы, иРНК-репликонсодержит 5' репликационнуюпоследовательностьраспознаванияальфавируса, открытуюрамкусчитывания, кодирующуюпредставляющийинтересбелок, и 3' репликационнуюпоследовательностьраспознаванияальфавируса. 5 н. и 10 з.п. ф-лы, 8 ил., 7 пр.

5. 发明专利

HK1259449A1 用於多功能和有效的基因表達的RNA複製子未知
公开(公告)号：HK1259449A1
公开(公告)日：2019-11-29
申请号：HK19101854
申请日：2019-02-01
申请人： BIONTECH RNA PHARMACEUTICALS GMBH , TRON TRANSLATIONALE ONKOLOGIE AN DER UNIV DER JOHANNES GUTENBERG UNIV MAINZ GEMEINNUETZIGE GMBH
发明人： BEISSERT TIM , SAHIN UGUR , PERKOVIC MARIO
IPC分类号： C12N20060101

6. 发明专利

CA3075696A1 METHOD OF ENHANCING RNA EXPRESSION IN A CELL 未知
公开(公告)号：CA3075696A1
公开(公告)日：2019-03-21
申请号：CA3075696
申请日：2018-09-11
申请人： BIONTECH RNA PHARMACEUTICALS GMBH , TRON TRANSLATIONALE ONKOLOGIE AN DER UNIV DER JOHANNEGUTENBERG UNIVERISTAT MAINZ GEMEINNUTZIGE GMBH
发明人： POLEGANOV MARCO ALEXANDER , PERKOVIC MARIO , SAHIN UGUR , BEISSERT TIM , KUHN ANDREAS
IPC分类号： C07K14/005 , C12N5/074
摘要： The present invention describes a virus-derived factor which when provided to cells, e.g., by transfecting the cells with RNA encoding the virus-derived factor, enhances expression of RNA encoding a peptide or protein in the cells. In particular, the virus- derived factor enhances survival of cells, in particular when transfected repetitively with RNA, and reduces an IFN response of cells to transfected RNA. Accordingly, the present invention provides methods and means for enhancing expression of RNA in cells. The cells are preferably transfected with the RNA.

7. 发明专利

RU2748892C2 РНК-РЕПЛИКОН ДЛЯ УНИВЕРСАЛЬНОЙ И ЭФФЕКТИВНОЙ ГЕННОЙ ЭКСПРЕССИИ 未知
公开(公告)号：RU2748892C2
公开(公告)日：2021-06-01
申请号：RU2018131966
申请日：2017-03-13
申请人： BIONTECH RNA PHARMACEUTICALS GMBH
发明人： BEISSERT TIM , SAHIN UGUR , PERKOVIC MARIO
IPC分类号： C12N15/86 , C12N5/10 , C12N15/85
摘要： Изобретениеотноситсяк областибиотехнологии. Описанагруппаизобретений, включающаяРНК-репликондляэкспрессиибелка, системутранс-репликациидляэкспрессиибелка, включающуювышеуказанныйРНК-репликон, ДНКдляиспользованияв качествематрицыдлятранскрипцииin vivoилиin vitro, способполученияпредставляющегоинтересбелкав клетке (варианты), клетку-хозяиндляполучениябелка, способполученияпредставляющегоинтересбелкау субъекта (варианты). ВодномизвариантовреализацииРНК-репликонсодержитмодифицированную 5' репликационнуюпоследовательностьраспознаванияальфавируса, причем 5' репликационнаяпоследовательностьраспознаваниямодифицированапосредствомудалениявсехинициирующихтрансляциюкодоновпосравнениюс нативнойальфавирусной 5' репликационнойпоследовательностьюраспознавания, гдеальфавируспредставляетсобойвируслесаСемликииливирусСинбис. Изобретениерасширяетарсеналсредствдлярепликациибелка. 8 н. и 15 з.п. ф-лы, 9 ил., 8 пр.

8. 发明专利

MA44479A ARN TRANSREPLIQUANT 未知
公开(公告)号：MA44479A
公开(公告)日：2021-04-21
申请号：MA44479
申请日：2017-03-13
申请人： BIONTECH RNA PHARMACEUTICALS GMBH , TRON TRANSLATIONALE ONKOLOGIE AN DER UNIV DER JOHANNES GUTENBERG UNIV MAINZ GEMEINNUETZIGE GMBH
发明人： BEISSERT TIM , PERKOVIC MARIO , SAHIN UGUR
IPC分类号： A61K48/00 , C12N5/10 , C12N15/40 , C12N15/86

9. 发明专利

SG11201807374WA RNA REPLICON FOR VERSATILE AND EFFICIENT GENE EXPRESSION 未知
公开(公告)号：SG11201807374WA
公开(公告)日：2018-10-30
申请号：SG11201807374W
申请日：2017-03-13
申请人： BIONTECH RNA PHARMACEUTICALS GMBH , TRON TRANSLATIONALE ONKOLOGIE AN DER UNIV DER JOHANNES GUTENBERG UNIV MAINZ GEMEINNUETZIGE GMBH
发明人： BEISSERT TIM , SAHIN UGUR , PERKOVIC MARIO
IPC分类号： C12N15/86 , C12N5/10 , C12N15/85
摘要： The present invention embraces a RNA replicon that can be replicated by a replicase of alphavirus origin. The RNA replicon comprises sequence elements required for replication by the replicase, but these sequence elements do not encode any protein or fragment thereof, such as an alphavirus non-structural protein or fragment thereof. Thus, in the RNA replicon according to the invention, sequence elements required for replication by the replicase and protein-coding region(s) are uncoupled. According to the present invention the uncoupling is achieved by the removal of at least one initiation codon compared to a native alphavirus genomic RNA. In particular, the RNA replicon comprises a 5' replication recognition sequence, wherein the 5' replication recognition sequence is characterized in that it comprises the removal of at least one initiation codon compared to a native aiphavirus 5' replication recognition sequence. The replicase of alphavirus origin may be encoded by an open reading frame on the RNA replicon or on a separate RNA molecule. The present invention enables efficient and safe expression of a protein of interest in a cell or organism, but is not associated with undesired production of fragments of alphavirus non-structural protein. Methods of protein productionin vitroandin vivo, as well as medical uses, are provided herein.

10. 发明专利

DK3433369T3 RNA-REPLIKON TIL VARIERET OG EFFEKTIV GENEKSPRESSION 未知
公开(公告)号：DK3433369T3
公开(公告)日：2020-03-30
申请号：DK17710528
申请日：2017-03-13
申请人： BIONTECH RNA PHARMACEUTICALS GMBH , TRON TRANSLATIONALE ONKOLOGIE AN DER UNIV DER JOHANNES GUTENBERG UNIV MAINZ GEMEINNUETZIGE GMBH
发明人： BEISSERT TIM , SAHIN UGUR , PERKOVIC MARIO
IPC分类号： C12N15/86 , C12N5/10 , C12N15/85

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