公开(公告)号：WO2022115547A1

公开(公告)日：2022-06-02

申请号：PCT/US2021/060745

申请日：2021-11-24

Applicant: TRANSLATE BIO, INC.

Inventor： KARVE, Shrirang ,  SARODE, Ashish ,  MONTOYA, Natalia, Vargas ,  PATEL, Priyal ,  DEROSA, Frank

IPC: A61K9/00 ,  A61K9/127 ,  A61K31/7088 ,  A61K31/7105 ,  C12N15/88

Abstract: 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：WO2021231901A1

公开(公告)日：2021-11-18

申请号：PCT/US2021/032513

申请日：2021-05-14

Applicant: TRANSLATE BIO, INC.

Inventor： KARVE, Shrirang ,  DEROSA, Frank ,  VARGAS MONTOYA, Natalia ,  KHANMOHAMMED, Asad

IPC: A61K9/00 ,  A61K9/127 ,  A61K9/51 ,  A61K31/7105 ,  C12N15/88

Abstract: The present invention provides, among other things, methods of encapsulating messenger RNA in lipid nanoparticles without the use of flammable solvents, and compositions produced by these methods, for mRNA delivery in therapeutic use. The present invention is, in part, based on the surprising discovery that mRNA can be encapsulated with high efficiency, without using an ethanol solvent, in the presence of an amphiphilic polymer. Thus, the present invention provides safe, cost-effective, and efficient methods of producing LNP formulations from large scale manufacturing processes as well as in low volume formulations for therapeutic applications.

公开(公告)号：WO2021127641A1

公开(公告)日：2021-06-24

申请号：PCT/US2020/066431

申请日：2020-12-21

Applicant: TRANSLATE BIO, INC.

Inventor： KARVE, Shrirang ,  DEROSA, Frank ,  SARODE, Ashish ,  MONTOYA, Natalia, Vargas ,  PATEL, Priyal

IPC: A61K9/127 ,  A61K38/18 ,  A61K31/7105 ,  A61K38/00 ,  A61K9/0019 ,  A61K9/1272 ,  A61K9/5192 ,  B82Y40/00 ,  B82Y5/00

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 combining a solution of preformed lipid nanoparticles with lipid nanoparticles encapsulating mRNA, resulting in a composition of increased potency of mRNA encoded protein expression in vivo.

公开(公告)号：WO2021055609A1

公开(公告)日：2021-03-25

申请号：PCT/US2020/051277

申请日：2020-09-17

Applicant: TRANSLATE BIO, INC.

Inventor： WOOSTER, Richard ,  DEROSA, Frank ,  BOEGLIN, Lianne ,  NANDURI, Priyaanka ,  DIAS, Anusha ,  TRAN, Khang Anh

IPC: C12N15/00 ,  A61K38/00 ,  C07K14/435

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

公开(公告)号：WO2021007278A1

公开(公告)日：2021-01-14

申请号：PCT/US2020/041122

申请日：2020-07-08

Applicant: TRANSLATE BIO, INC.

Inventor： KARVE, Shrirang ,  SARODE, Ashish ,  DEROSA, Frank

IPC: A61K9/127 ,  A61K9/51 ,  A61K38/18 ,  A61K47/69 ,  A61K48/00 ,  C12N15/88

Abstract: The present invention provides an improved lipid nanoparticle formulation encapsulating mRNA comprising DEPE as a helper lipid.

公开(公告)号：WO2020243540A1

公开(公告)日：2020-12-03

申请号：PCT/US2020/035275

申请日：2020-05-29

Applicant: TRANSLATE BIO, INC.

Inventor： ZHANG, Yi ,  KARVE, Shrirang ,  DEROSA, Frank ,  HEARTLEIN, Michael

IPC: C07D321/00 ,  C07D323/00 ,  C07D405/06 ,  C07D493/10 ,  C07C219/06 ,  A61P43/00 ,  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：WO2020106903A1

公开(公告)日：2020-05-28

申请号：PCT/US2019/062504

申请日：2019-11-20

Applicant: TRANSLATE BIO, INC.

Inventor： DEROSA, Frank ,  KARVE, Shrirang ,  ZHANG, Yi

IPC: C07C215/24 ,  A61K9/127 ,  A61K31/7105 ,  A61K35/15 ,  A61K47/18 ,  A61K47/50 ,  A61K48/00 ,  C12N15/88

Abstract: The compounds disclosed herein compound of Formula (I), substructures thereof, and pharmaceutically acceptable salts 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：WO2020097379A3

公开(公告)日：2020-05-14

申请号：PCT/US2019/060339

申请日：2019-11-07

Applicant: TRANSLATE BIO, INC.

Inventor： KARVE, Shrirang ,  ZHANG, Yi ,  DEROSA, Frank ,  HEARTLEIN, Michael

IPC: A61K47/54 ,  A61K47/60 ,  A61K47/69

Abstract: The compounds disclosed herein ( e.g. , compounds having a structure according to Formula (I/ (II)/ (III)/ (IV), and (V)) are polymers wherein an organic polymeric segment ( e.g ., a polyethylene glycol (PEG) group) comprises covalent attachments to two or more lipid substructures, and each lipid substructure independently comprises a hydrophobic moiety and a hydrophilic moiety. 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：WO2019222277A1

公开(公告)日：2019-11-21

申请号：PCT/US2019/032300

申请日：2019-05-14

Applicant: TRANSLATE BIO, INC.

Inventor： KARVE, Shrirang ,  DEROSA, Frank ,  BHAVSAR, Zarna ,  HEARTLEIN, Michael

IPC: A61P43/00 ,  A61K38/47 ,  A61K48/00

Abstract: The present invention provides, among other things, methods of formulating nucleic acid-containing nanoparticles with an mRNA encoding an enzyme to afford efficient delivery of payload to a cell or tissue of interest via subcutaneous administration. The resulting payload can be efficiently delivered to the liver and other organs or tissues of a treated subject.

公开(公告)号：WO2018089790A1

公开(公告)日：2018-05-17

申请号：PCT/US2017/061100

申请日：2017-11-10

Applicant: TRANSLATE BIO, INC.

Inventor： DEROSA, Frank ,  HEARTLEIN, Michael ,  KARVE, Shrirang

IPC: A61K9/00 ,  A61K47/28 ,  A61K9/127 ,  A61K48/00

Abstract: The present invention provides, among other things, compositions and methods of formulating nucleic acid-containing nanoparticles comprising no more than three distinct lipids components, one distinct lipid component being a sterol-based cationic lipid. In some embodiments, the present invention provides compositions and methods in which the lipid nanoparticles further comprise helper lipids and PEG-modified lipids. The resulting formulation comprises a high encapsulation percentage for nucleic acids.

Abstract translation: 本发明提供了包含不多于三种不同脂质组分的含核酸纳米颗粒的组合物和方法，其中一种不同的脂质组分是基于甾醇的阳离子脂质。 在一些实施方案中，本发明提供了其中脂质纳米颗粒进一步包含辅助脂质和PEG修饰的脂质的组合物和方法。 所得到的制剂包含核酸的高包封率。