公开(公告)号：US11559561B2

公开(公告)日：2023-01-24

申请号：US16736417

申请日：2020-01-07

申请人： Translate Bio, Inc.

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

IPC分类号： A61K9/127 ,  A61K31/7105 ,  A61K38/17 ,  A61K9/00 ,  A61P11/00 ,  A61K31/711

摘要： 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：US11547666B2

公开(公告)日：2023-01-10

申请号：US17058334

申请日：2019-05-30

申请人： Translate Bio, Inc.

发明人： Yi Zhang ,  Shrirang Karve ,  Frank DeRosa ,  Michael Heartlein

IPC分类号： A61K9/127 ,  A61K9/00 ,  C07J41/00 ,  A61K39/00 ,  A61K38/45 ,  A61K38/52 ,  A61K39/385

摘要： 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：US11497716B2

公开(公告)日：2022-11-15

申请号：US17003105

申请日：2020-08-26

申请人： TRANSLATE BIO, INC.

发明人： Frank DeRosa ,  Braydon Charles Guild ,  Michael Heartlein

IPC分类号： A61K9/127 ,  C12N15/11 ,  A61K38/44 ,  A61K47/28 ,  A61K48/00

摘要： Disclosed herein are novel lipids and liposomal compositions prepared using such compounds and related methods of neutralizing or otherwise modifying such liposomal compositions. The lipids described herein are useful for example, as liposomal vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and the subsequent transfection of such target cells. In certain embodiments, one or more of the compounds that comprise the liposomal delivery vehicle may be neutralized or further modified such that the properties of the liposomal delivery vehicle are modified.

公开(公告)号：US20220347099A1

公开(公告)日：2022-11-03

申请号：US17162656

申请日：2021-01-29

申请人： Translate Bio, Inc. ,  Massachusetts Institute of Technology

发明人： Michael Heartlein ,  Daniel Anderson ,  Yizhou Dong ,  Frank DeRosa

IPC分类号： A61K9/127 ,  A61K48/00 ,  A61K38/17 ,  A61K38/48 ,  A61K38/53

摘要： The present invention provides, among other things, methods of delivering mRNA in vivo, including administering to a subject in need of delivery a composition comprising an mRNA encoding a protein, encapsulated within a liposome such that the administering of the composition results in the expression of the protein encoded by the mRNA in vivo, wherein the liposome comprises a cationic lipid of formula I-c: or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20220324926A1

公开(公告)日：2022-10-13

申请号：US17693120

申请日：2022-03-11

申请人： Translate Bio, Inc.

发明人： Shrirang Karve ,  Frank DeRosa ,  Michael Heartlein ,  Zarna Patel

IPC分类号： C07K14/47 ,  A61K9/00 ,  A61K9/51 ,  A61K9/127 ,  A61K9/19 ,  A61K47/26 ,  A61K45/06 ,  B82Y5/00 ,  A61P11/00

摘要： The present invention provides, among other things, an improved method of treating cystic fibrosis (CF) in a human subject. The method comprises administering a composition comprising an mRNA encoding a Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein at a concentration of 0.5 mg/mL or greater to a human subject via nebulization. The composition is aerosolized using a nebulizer and a nominal dose of the mRNA is administered to the human subject via the nebulizer over a period of time, typically at least 30 minutes, at a suitable nebulization rate, e.g., at least 0.2 mL/minute.

公开(公告)号：US20220287966A1

公开(公告)日：2022-09-15

申请号：US17534956

申请日：2021-11-24

申请人： Translate Bio, Inc.

发明人： Shrirang Karve ,  Ashish Sarode ,  Natalia Vargas Montoya ,  Priyal Patel ,  Frank DeRosa

IPC分类号： A61K9/127 ,  A61K39/00

摘要： The present invention provides, among other things, a liquid lipid nanoparticle (LNP) formulation encapsulating mRNA encoding a peptide or polypeptide, that is resistant to aggregation and to mRNA degradation following multiple rounds of freezing at −20° C. and rethawing.

公开(公告)号：US11433144B2

公开(公告)日：2022-09-06

申请号：US17141744

申请日：2021-01-05

申请人： Translate Bio, Inc.

发明人： Frank DeRosa ,  Michael Heartlein

IPC分类号： C07D319/12 ,  A61K48/00 ,  C12N15/11 ,  A61K9/127 ,  A61K38/18 ,  A61K38/48

摘要： The present invention provides, in part, a biodegradable compound of formula I, and sub-formulas thereof:Formula (I) or a pharmaceutically acceptable salt thereof, where each X independently is O or S, each Y independently is O or S, and each R1 independently is defined herein; and a liposome composition comprising the cationic lipid of formula I or a sub-formula thereof, and methods of delivering agents, such as nucleic acids including mRNA, in vivo, by administering to a subject the liposome comprising the cationic lipid of formula I or a sub-formula thereof, where the agent is encapsulated within the liposome.

公开(公告)号：US20220226236A1

公开(公告)日：2022-07-21

申请号：US17389016

申请日：2021-07-29

申请人： TRANSLATE BIO, INC. ,  Ethris GmbH

发明人： Michael Heartlein ,  Braydon Charles Guild ,  Frank DeRosa ,  Carsten Rudolph ,  Christian Plank

IPC分类号： A61K9/00 ,  C12N15/88 ,  A61K31/7088 ,  A61M15/00 ,  A61M16/14

摘要： Compositions comprising mRNA formulated for pulmonary administration and related methods for delivery of the mRNA and/or encoded protein to a non-lung cell or tissue. The compositions and methods may be used to prevent or ameliorate the symptoms of diseases associated with the mRNA encoded protein.

公开(公告)号：US11377642B2

公开(公告)日：2022-07-05

申请号：US16245828

申请日：2019-01-11

申请人： Translate Bio, Inc.

发明人： Frank DeRosa ,  Michael Heartlein ,  Anusha Dias

IPC分类号： A61K38/44 ,  C12N15/00 ,  C12N9/02 ,  A61K9/127 ,  A61K48/00

摘要： 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：US20220193247A1

公开(公告)日：2022-06-23

申请号：US17570352

申请日：2022-01-06

申请人： Translate Bio, Inc.

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

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

摘要： 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.