公开(公告)号：US11692189B2

公开(公告)日：2023-07-04

申请号：US17835725

申请日：2022-06-08

Applicant: Translate Bio, Inc.

Inventor： Frank DeRosa ,  Anusha Dias ,  Michael Heartlein ,  Shrirang Karve

IPC: C12N15/10 ,  C07H21/02

CPC classification number: C12N15/10 ,  C07H21/02 ,  C12N15/1017

Abstract: The present invention provides, among other things, methods of purifying messenger RNA (mRNA) including the steps of subjecting an impure preparation comprising in vitro synthesized mRNA to a denaturing condition, and purifying the mRNA from the impure preparation from step (a) by tangential flow filtration, wherein the mRNA purified from step (b) is substantially free of prematurely aborted RNA sequences and/or enzyme reagents used in in vitro synthesis.

公开(公告)号：US20220364145A1

公开(公告)日：2022-11-17

申请号：US17746657

申请日：2022-05-17

Applicant: Translate Bio, Inc.

Inventor： Frank DeRosa ,  Anusha Dias ,  Michael Heartlein

IPC: C12Q1/68 ,  C12Q1/6823 ,  C07K14/505 ,  C12N9/02

Abstract: The present invention provides, among other things, methods of quantitating mRNA capping efficiency, particularly for mRNA synthesized in vitro. In some embodiments, the methods comprise chromatographic methods of quantifying capping efficiency and methylation status of the caps.

公开(公告)号：US20220087935A1

公开(公告)日：2022-03-24

申请号：US17420346

申请日：2020-01-07

Applicant: Translate Bio, Inc.

Inventor： Anusha Dias ,  Darshan Parekh ,  Jeffrey S. Dubins ,  Christian Cobaugh ,  Shrirang Karve ,  Zarna Patel ,  Sara J. Dunaj ,  Frank DeRosa ,  Michael Heartlein

IPC: A61K9/127 ,  A61K31/711 ,  A61P11/00

Abstract: The present invention provides, among other things, methods and compositions for treating primary ciliary dyskinesia (PCD) based on mRNA therapy. The compositions used in treatment of PCD comprise an mRNA comprising a dynein axonemal heavy chain 5 (DNAH5) coding sequence and are administered at an effective dose and an administration interval such that at least one symptom or feature of PCD is reduced in intensity, severity, or frequency or has a delayed onset. mRNAs with optimized DNAH5 coding sequences are provided that can be administered without the need for modifying the nucleotides of the mRNA to achieve sustained in vivo function.

公开(公告)号：US11253605B2

公开(公告)日：2022-02-22

申请号：US15907131

申请日：2018-02-27

Applicant: Translate Bio, Inc.

Inventor： Anusha Dias ,  Jonathan Abysalh ,  Brian Bettencourt ,  Frank DeRosa ,  Michael Heartlein

IPC: A61K47/69 ,  A61K47/64 ,  A61K9/127 ,  C12N15/10 ,  A61K38/17 ,  C07K14/47 ,  A61P11/00 ,  A61K9/00 ,  A61K31/7105

Abstract: The present invention provides, among other things, improved methods and pharmaceutical compositions for treating cystic fibrosis based on codon optimized mRNA encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein.

公开(公告)号：US20210371900A1

公开(公告)日：2021-12-02

申请号：US17325092

申请日：2021-05-19

Applicant: Translate Bio, Inc.

Inventor： Michael Heartlein ,  Frank DeRosa ,  Anusha Dias

IPC: C12Q1/6804

Abstract: The present invention provides, among other things, methods of quantitating mRNA capping efficiency, particularly mRNA synthesized in vitro. In some embodiments, methods according to the present invention comprise providing an mRNA sample containing capped and uncapped mRNA, providing a cap specific binding substance under conditions that permit the formation of a complex between the cap specific binding substance and the capped mRNA, and quantitatively determining the amount of the complex as compared to a control, thereby quantifying mRNA capping efficiency.

公开(公告)号：US11104934B2

公开(公告)日：2021-08-31

申请号：US16744985

申请日：2020-01-16

Applicant: Translate Bio, Inc.

Inventor： Michael Heartlein ,  Frank DeRosa ,  Anusha Dias

IPC: C12Q1/68 ,  C12Q1/6804

Abstract: The present invention provides, among other things, methods of quantitating mRNA capping efficiency, particularly mRNA synthesized in vitro. In some embodiments, methods according to the present invention comprise providing an mRNA sample containing capped and uncapped mRNA, providing a cap specific binding substance under conditions that permit the formation of a complex between the cap specific binding substance and the capped mRNA, and quantitatively determining the amount of the complex as compared to a control, thereby quantifying mRNA capping efficiency.

公开(公告)号：US10975369B2

公开(公告)日：2021-04-13

申请号：US15907086

申请日：2018-02-27

Applicant: Translate Bio, Inc.

Inventor： Frank DeRosa ,  Michael Heartlein ,  Jonathan Abysalh ,  Daniel Crawford ,  Anusha Dias ,  Shrirang Karve

IPC: C12Q1/68 ,  C07H21/00 ,  C12N15/10 ,  C07H21/04

Abstract: The present invention relates, in part, to methods for large-scale purification of mRNA. The method includes, at least, a step of centrifuging an mRNA suspension in a centrifuge comprising a porous substrate at a speed sufficient to remove process contaminants and to precipitate purified mRNA composition onto the porous substrate.

公开(公告)号：US20190211314A1

公开(公告)日：2019-07-11

申请号：US16245828

申请日：2019-01-11

Applicant: Translate Bio, Inc.

Inventor： Frank DeRosa ,  Michael Heartlein ,  Anusha Dias

IPC: C12N9/02 ,  A61K48/00 ,  A61K38/44 ,  A61K9/127

CPC classification number: C12N9/0071 ,  A61K9/1272 ,  A61K38/44 ,  A61K48/00 ,  A61K48/0033 ,  A61K48/005 ,  C12Y114/16001

Abstract: The present invention provides, among other things, methods of treating phenylketonuria (PKU), including administering to a subject in need of treatment a composition comprising an mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose and an administration interval such that at least one symptom or feature of PKU is reduced in intensity, severity, or frequency or has delayed in onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

公开(公告)号：US20180333457A1

公开(公告)日：2018-11-22

申请号：US15981757

申请日：2018-05-16

Applicant: Translate Bio, Inc.

Inventor： Michael Heartlein ,  Frank DeRosa ,  Alan Kimura ,  Jonathan Abysalh ,  Anusha Dias ,  Shrirang Karve ,  Zarna Patel

IPC: A61K38/17 ,  A61K9/00 ,  A61K9/127 ,  A61P11/12

CPC classification number: A61K38/1709 ,  A61K9/0078 ,  A61K9/127 ,  A61K48/0075 ,  A61P11/12

Abstract: The present invention provides, among other things, methods of treating cystic fibrosis, comprising a step of administering to a subject in need of treatment a composition comprising an mRNA encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, wherein the mRNA encoding the CFTR protein comprises a polynucleotide sequence at least 80% identical to SEQ ID NO: 1, wherein the mRNA is at a concentration of at least 0.4 mg/mL, and wherein the step of administering comprises inhalation.

公开(公告)号：US20180291425A1

公开(公告)日：2018-10-11

申请号：US15936293

申请日：2018-03-26

Applicant: Translate Bio, Inc.

Inventor： Michael Heartlein ,  Frank DeRosa ,  Anusha Dias

IPC: C12Q1/68 ,  C12N9/02 ,  C07K14/505 ,  C12Q1/6823

Abstract: The present invention provides, among other things, methods of quantitating mRNA capping efficiency, particularly for mRNA synthesized in vitro. In some embodiments, the methods comprise chromatographic methods of quantifying capping efficiency and methylation status of the caps.