公开(公告)号：US20190092828A1

公开(公告)日：2019-03-28

申请号：US16049212

申请日：2018-07-30

Applicant: ModernaTX, Inc.

Inventor： Stephen G. HOGE ,  William Joseph ISSA ,  Edward John MIRACCO ,  Jennifer NELSON ,  John REYNDERS ,  Matthew STANTON

IPC: C07K14/535 ,  C07K14/505 ,  C12P19/34 ,  A61K48/00 ,  C12N9/02 ,  C12P21/02

Abstract: The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them. In some aspects, the disclosure provides mRNA wherein the uracil content has been modified and which may be particularly effective for use in therapeutic compositions, because they may benefit from both high expression levels and limited induction of the innate immune response. In some aspects, the disclosure provides methods for the production of pharmaceutical compositions including mRNA without reverse phase chromatography.

公开(公告)号：US20230203086A1

公开(公告)日：2023-06-29

申请号：US17854187

申请日：2022-06-30

Applicant: ModernaTX, Inc.

Inventor： William Joseph ISSA ,  John Grant AUNINS ,  Stephane BANCEL

IPC: C07H21/02 ,  C12Q1/6806 ,  C12N15/10 ,  C07H1/06 ,  C08B37/00

CPC classification number: C07H21/02 ,  C07H1/06 ,  C08B37/0039 ,  C12N15/1006 ,  C12Q1/6806

Abstract: Disclosed herein are methods for purifying RNA comprising poly A. Also disclosed herein are compositions such as surfaces and oligonucleotides for purifying RNA comprising polyA. Other embodiments are also disclosed. Commercially-available resins having polythymidine oligonucleotide ligands typically contain less than 30 thymidine (2′deoxy) residues and some commercial resin suppliers utilize a distribution of dT chain lengths, not of a discreet length.

公开(公告)号：US20190085368A1

公开(公告)日：2019-03-21

申请号：US16144282

申请日：2018-09-27

Applicant: ModernaTX, Inc.

Inventor： Stephane BANCEL ,  William Joseph ISSA ,  John Grant AUNINS ,  Tirtha CHAKRABORTY

IPC: C12P19/34 ,  C12N15/10 ,  C12Q1/6865

Abstract: Described are methods for production of RNA transcripts using a non-amplified, linearized DNA tempate in an in vitro transcription reaction. Enzymatic 5′ capping and oligo dT purification can also be included in the methods.

公开(公告)号：US20210230578A1

公开(公告)日：2021-07-29

申请号：US17113940

申请日：2020-12-07

Applicant: ModernaTX, Inc.

Inventor： William Joseph ISSA ,  Yuxun WANG ,  Stephane BANCEL

IPC: C12N15/10 ,  C12Q1/6806

Abstract: The present invention describes methods of removing DNA from an RNA transcript during the mRNA production process. The method embodies procedures for obtaining an in vitro transcription product, and removing any DNA from the product. The DNA can be removed by adding either free DNase or a resin containing immobilized DNase to the product, and recovering the RNA transcript. Alternatively, the DNA template used in the in vitro transcription reaction is labeled. After transcription, the product is applied to a resin that is configured to bind the label, and the RNA transcript is recovered. To detect whether any residual impurities are left in the RNA transcript product, the product is subjected to nuclease digestion and subsequently to liquid chromatography-tandem mass spectrometry analysis to quantitate any residual DNA. The present invention demonstrates efficient and effective methods of isolating an RNA transcript from an in vitro transcription product.

公开(公告)号：US20190100748A1

公开(公告)日：2019-04-04

申请号：US16049132

申请日：2018-07-30

Applicant: ModernaTX, Inc.

Inventor： William Joseph ISSA ,  Yuxun WANG ,  Stephane BANCEL

IPC: C12N15/10 ,  C12Q1/6806

Abstract: The present invention describes methods of removing DNA from an RNA transcript during the mRNA production process. The method embodies procedures for obtaining an in vitro transcription product, and removing any DNA from the product. The DNA can be removed by adding either free DNase or a resin containing immobilized DNase to the product, and recovering the RNA transcript. Alternatively, the DNA template used in the in vitro transcription reaction is labeled. After transcription, the product is applied to a resin that is configured to bind the label, and the RNA transcript is recovered. To detect whether any residual impurities are left in the RNA transcript product, the product is subjected to nuclease digestion and subsequently to liquid chromatography-tandem mass spectrometry analysis to quantitate any residual DNA. The present invention demonstrates efficient and effective methods of isolating an RNA transcript from an in vitro transcription product.