公开(公告)号：US20220389403A1

公开(公告)日：2022-12-08

申请号：US17835710

申请日：2022-06-08

Applicant: Translate Bio, Inc.

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

IPC: C12N15/10 ,  C07H21/02

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：US20220323542A1

公开(公告)日：2022-10-13

申请号：US17631322

申请日：2020-07-30

Applicant: Translate Bio, Inc.

Inventor： Ann Barbier ,  Michael Heartlein ,  Frank DeRoss ,  Jonathan Abysalh ,  Anusha Dias ,  Shrirang Karve ,  Zama Patel

IPC: A61K38/17 ,  A61P11/00 ,  A61K9/00 ,  A61P43/00 ,  A61K31/47 ,  A61K31/443

Abstract: The present invention provides, among other things, an improved method of treating cystic fibrosis (CF) in a human subject. The method comprises administration of a composition comprising an mRNA encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein by nebulization at a dose between 7 mg and 25 mg. A suitable dose for use in the method of the invention is selected on the basis that it provides the human subject with at least a 3% increase in absolute change in ppFEV1 (percent predicted forced expiratory volume in one second) from baseline ppFEV1 at two days following the administration. In addition or alternatively, the dose is selected to provide the human subject with at least a 2% increase in absolute change in ppFEV1 from baseline ppFEV1 at one week following the administration. In addition or alternatively, the dose is selected to provide the human subject with at least a 4% maximum increase in absolute change in ppFEV1 from baseline ppFEV1 through one week following administration.

公开(公告)号：US20220233444A1

公开(公告)日：2022-07-28

申请号：US17605343

申请日：2020-04-21

Applicant: Translate Bio, Inc.

Inventor： Shrirang Karve ,  Yi Zhang ,  Frank DeRosa

IPC: A61K9/127 ,  C07C327/22 ,  A61K48/00 ,  A61K38/45 ,  A61K38/17

Abstract: The present invention provides, in part, thioester cationic lipid compounds of formula A, and sub-formulas thereof: or a pharmaceutically acceptable salt thereof. The compounds provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

公开(公告)号：US20220226255A1

公开(公告)日：2022-07-21

申请号：US17539659

申请日：2021-12-01

Applicant: Translate Bio, Inc.

Inventor： Frank DeRosa ,  Shrirang Karve ,  Michael Heartlein

IPC: A61K9/50 ,  A61K9/127 ,  A61K31/713

Abstract: The present invention provides an improved process for lipid nanoparticle formulation and mRNA encapsulation. In some embodiments, the present invention provides a process of encapsulating messenger RNA (mRNA) in lipid nanoparticles comprising a step of mixing a mRNA solution and a lipid solution, wherein the mRNA solution and/or the lipid solution are at a pre-determined temperature greater than ambient temperature.

公开(公告)号：US20220226244A1

公开(公告)日：2022-07-21

申请号：US17614096

申请日：2020-05-29

Applicant: Translate Bio, Inc.

Inventor： Yi Zhang ,  Shrirang Karve ,  Frank DeRosa ,  Michael Heartlein

IPC: A61K9/127 ,  A61K38/45 ,  A61K38/17 ,  A61K39/385 ,  C07D321/00 ,  C07D405/06 ,  C07D405/14 ,  C07D493/20 ,  C07C229/12 ,  A61K48/00

Abstract: Disclosed are cationic lipids which are compounds of Formula I. Cationic lipids provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

公开(公告)号：US20220135608A1

公开(公告)日：2022-05-05

申请号：US17344535

申请日：2021-06-10

Applicant: Translate Bio, Inc.

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

IPC: C07H1/06 ,  C07H21/00 ,  C12N15/10 ,  C07H21/02

Abstract: The present invention provides, among other things, methods of purifying messenger RNA (mRNA) including the steps of (a) precipitating mRNA from an impure preparation; (b) subjecting the impure preparation comprising precipitated mRNA to a purification process involving membrane filtration such that the precipitated mRNA is captured by a membrane; and (c) eluting the captured precipitated mRNA from the membrane by re-solubilizing the mRNA, thereby resulting in a purified mRNA solution. In some embodiments, a purification process involving membrane filtration suitable for the present invention is tangential flow filtration.

公开(公告)号：US20220016265A1

公开(公告)日：2022-01-20

申请号：US17292673

申请日：2019-11-08

Applicant: Translate Bio, Inc.

Inventor： John R. Androsavich ,  Frank DeRosa ,  Shrirang Karve

IPC: A61K48/00 ,  A61K9/51 ,  A61K9/00

Abstract: The present invention provides, among other things, a method of ocular delivery of messenger RNA (mRNA), comprising administering into an eye of a subject in need of delivery a composition comprising an mRNA encoding a protein, such that the administration of the composition results in expression of the protein encoded by the mRNA in the eye.

公开(公告)号：US11167043B2

公开(公告)日：2021-11-09

申请号：US16228596

申请日：2018-12-20

Applicant: Translate Bio, Inc.

Inventor： Kim Askew ,  Jou-Ku Chung ,  Frank DeRosa ,  Michael Heartlein ,  Shrirang Karve ,  Thomas McCauley ,  Lianne Smith ,  Ann J. Barbier

IPC: A61K48/00 ,  C12N15/85 ,  C12N15/52 ,  A61K47/69 ,  A61K9/127 ,  A61K9/00 ,  A61K38/45 ,  A61P3/00

Abstract: The present invention provides, among other things, methods of treating ornithine transcarbamylase deficiency, including administering to a subject in need of treatment a composition comprising an mRNA encoding an ornithine transcarbamylase protein at a low dose and at an administration interval such that at least one symptom or feature of the OTC deficiency is reduced.

公开(公告)号：US20210275689A1

公开(公告)日：2021-09-09

申请号：US17185587

申请日：2021-02-25

Applicant: Translate Bio, Inc.

Inventor： Shrirang Karve ,  Ashish Sarode ,  Frank DeRosa

IPC: A61K48/00 ,  A61K47/69 ,  A61K47/60 ,  A61K9/51 ,  B01J13/20 ,  B01F3/08 ,  B01F13/00

Abstract: The present invention provides an improved process for lipid nanoparticle formulation and mRNA encapsulation. In some embodiments, the present invention provides a process of encapsulating messenger RNA (mRNA) in lipid nanoparticles comprising a step of mixing a suspension of preformed lipid nanoparticles and mRNA.

公开(公告)号：US11059841B2

公开(公告)日：2021-07-13

申请号：US16196664

申请日：2018-11-20

Applicant: Translate Bio, Inc.

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

IPC: C12Q1/68 ,  C07H21/00 ,  C07H1/06 ,  C12N15/10 ,  C07H21/02

Abstract: The present invention provides, among other things, methods of purifying messenger RNA (mRNA) including the steps of (a) precipitating mRNA from an impure preparation; (b) subjecting the impure preparation comprising precipitated mRNA to a purification process involving membrane filtration such that the precipitated mRNA is captured by a membrane; and (c) eluting the captured precipitated mRNA from the membrane by re-solubilizing the mRNA, thereby resulting in a purified mRNA solution. In some embodiments, a purification process involving membrane filtration suitable for the present invention is tangential flow filtration.