公开(公告)号：US20240318187A1

公开(公告)日：2024-09-26

申请号：US18477788

申请日：2023-09-29

Applicant: ModernaTX, Inc.

Inventor： Stephen G. HOGE ,  Kerry BENENATO ,  Vladimir PRESNYAK ,  Iain MCFADYEN ,  Ellalahewage Sathyajith KUMARASINGHE ,  Staci SABNIS ,  William BUTCHER

IPC: C12N15/67 ,  A61K31/7115 ,  A61K48/00

CPC classification number: C12N15/67 ,  A61K31/7115 ,  A61K48/0066 ,  C12N2800/22

Abstract: The invention related to polyribonucleotides comprising an open reading frame of linked nucleosides encoding a polypeptide of interest (e.g., a therapeutic polypeptide), isoforms thereof, functional fragments thereof, and fusion proteins comprising the polypeptide. In some embodiments, the open reading frame is sequence-optimized. In particular embodiments, the invention provides sequence-optimized polyribonucleotides comprising nucleotides encoding the sequence of the polypeptide of interest, or sequence having high sequence identity with those sequence optimized polyribonucleotides.

公开(公告)号：US20190000933A1

公开(公告)日：2019-01-03

申请号：US16110833

申请日：2018-08-23

Applicant: ModernaTX, Inc.

Inventor： Paolo MARTINI ,  Stephen G. HOGE ,  Kerry BENENATO ,  Vladimir PRESNYAK ,  Iain MCFADYEN ,  Ellalahewage Sathyajith KUMARASINGHE ,  Xuling ZHU ,  Lin Tung GUEY ,  Staci SABNIS

IPC: A61K38/47 ,  A61K9/51 ,  A61P3/00

Abstract: The invention relates to mRNA therapy for the treatment of Fabry disease. mRNAs for use in the invention, when administered in vivo, encode human the α-galactosidase A (GLA), isoforms thereof, functional fragments thereof, and fusion proteins comprising GLA. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of GLA expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient GLA activity in subjects, namely Gb3 and lyso-Gb3.

公开(公告)号：US20230013773A1

公开(公告)日：2023-01-19

申请号：US17162061

申请日：2021-01-29

Applicant: ModernaTX, Inc.

Inventor： Stephen G. HOGE ,  Tirtha CHAKRABORTY ,  Joshua P. FREDERICK ,  Matthias JOHN ,  Antonin DE FOUGEROLLES

IPC: C07K14/47 ,  A61K48/00 ,  C12N15/85 ,  C12N15/113 ,  A61K31/7105 ,  A61K31/711

Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of signal-sensor polynucleotides, primary transcripts and mmRNA molecules.

公开(公告)号：US20220111079A1

公开(公告)日：2022-04-14

申请号：US17329368

申请日：2021-05-25

Applicant: ModernaTX, Inc.

Inventor： Stephen G. HOGE ,  Eric Yi-Chun HUANG ,  Tirtha CHAKRABORTY

IPC: A61K48/00 ,  C12N15/11 ,  C12N9/16 ,  C12N15/90

Abstract: The present invention relates to compositions comprising and methods of using synthetic polynucleotides, e.g., modified mRNA, encoding CRISPR related proteins including dCAS9 and synthetic sgRNAs targeting a gene of interest.

公开(公告)号：US20190382774A1

公开(公告)日：2019-12-19

申请号：US16300223

申请日：2017-05-18

Applicant: ModernaTX, Inc.

Inventor： Stephen G. HOGE ,  Kerry BENENATO ,  Vladimir PRESNYAK ,  Iain MCFADYEN ,  Ellalahewage Sathyajith KUMARASINGHE ,  Staci SABNIS ,  William BUTCHER

IPC: C12N15/67 ,  A61K31/7115 ,  A61K48/00

Abstract: The invention related to polyribonucleotides comprising an open reading frame of linked nucleosides encoding a polypeptide of interest (e.g., a therapeutic polypeptide), isoforms thereof, functional fragments thereof, and fusion proteins comprising the polypeptide. In some embodiments, the open reading frame is sequence-optimized. In particular embodiments, the invention provides sequence-optimized polyribonucleotides comprising nucleotides encoding the sequence of the polypeptide of interest, or sequence having high sequence identity with those sequence optimized polyribonucleotides.

公开(公告)号：US20190314291A1

公开(公告)日：2019-10-17

申请号：US16262758

申请日：2019-01-30

Applicant: ModernaTX, Inc.

Inventor： Gilles BESIN ,  Luis BRITO ,  Stephen G. HOGE ,  Edward HENNESSY ,  Mark CORNEBISE ,  Kerry BENENATO ,  Staci SABNIS ,  Michael W. DANNEMAN

IPC: A61K9/51 ,  C07K14/525 ,  A61P35/00 ,  C07K14/705 ,  A61K39/245

Abstract: The disclosure features immune cell delivery lipid nanoparticle (LNP) compositions that allow for enhanced delivery of agents, e.g., nucleic acids, such as therapeutic and/or prophylactic RNAs, to immune cells, in particular T cells, as well as B cells, dendritic cells and monocytes. The LNPs comprise an effective amount of an immune cell delivery potentiating lipid such that delivery of an agent by an immune cell delivery LNP is enhanced as compared to an LNP lacking the immune cell delivery potentiating agent. Methods of using the immune cell delivery LNPs for delivery of agents, e.g., nucleic acid delivery, for protein expression, for modulating immune cell activity and modulating immune responses are also disclosed.

公开(公告)号：US20220323482A1

公开(公告)日：2022-10-13

申请号：US17641469

申请日：2020-09-11

Applicant: ModernaTX, Inc.

Inventor： Allison AUGUST ,  Tal ZAKS ,  Stephen G. HOGE

IPC: A61K31/7105 ,  A61K9/00 ,  A61K9/127

Abstract: The disclosure features methods of treatment comprising systemic administration of mRNA encoding a therapeutic protein and delivered by lipid nanoparticle to human subjects.

公开(公告)号：US20190290742A1

公开(公告)日：2019-09-26

申请号：US16152945

申请日：2018-10-05

Applicant: ModernaTX, Inc.

Inventor： Tirtha CHAKRABORTY ,  Stephane BANCEL ,  Stephen G. HOGE ,  Atanu ROY ,  Antonin DE FOUGEROLLES ,  Noubar B. AFEYAN

IPC: A61K39/00 ,  C12N15/67

Abstract: The invention relates to compositions and methods for the manufacture and optimization of modified mRNA molecules via optimization of their terminal architecture.

公开(公告)号：US20190002890A1

公开(公告)日：2019-01-03

申请号：US16110309

申请日：2018-08-23

Applicant: ModernaTX, Inc.

Inventor： Paolo MARTINI ,  Stephen G. HOGE ,  Kerry BENENATO ,  Vladimir PRESNYAK ,  Iain MCFADYEN ,  Ellalahewage Sathyajith KUMARASINGHE ,  Xuling ZHU ,  Lin Tung GUEY ,  Staci SABNIS

IPC: C12N15/67 ,  C12N9/40 ,  A61K9/51

Abstract: The invention relates to mRNA therapy for the treatment of Fabry disease. mRNAs for use in the invention, when administered in vivo, encode human the α-galactosidase A (GLA), isoforms thereof, functional fragments thereof, and fusion proteins comprising GLA. mRNAs of the invention are preferably encapsulated in lipid nanoparticles (LNPs) to effect efficient delivery to cells and/or tissues in subjects, when administered thereto. mRNA therapies of the invention increase and/or restore deficient levels of GLA expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient GLA activity in subjects, namely Gb3 and lyso-Gb3.

公开(公告)号：US20180369374A1

公开(公告)日：2018-12-27

申请号：US15996146

申请日：2018-06-01

Applicant: ModernaTX, Inc.

Inventor： Joshua P. FREDERICK ,  Susannah HEWITT ,  Ailin BAI ,  Stephen G. HOGE ,  Vladimir PRESNYAK ,  Iain MCFADYEN ,  Kerry BENENATO ,  Ellalahewage Sathyajith KUMARASINGHE

IPC: A61K39/395 ,  A61K39/00

CPC classification number: A61K39/39558 ,  A61K31/713 ,  A61K39/0011 ,  A61K39/39 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/53 ,  A61K2039/585 ,  A61P35/00 ,  C07K14/54 ,  C07K14/5434 ,  C07K14/5443 ,  C07K14/705 ,  C07K14/70503 ,  C07K14/70532 ,  C07K14/70575 ,  C07K14/70596 ,  C07K16/2818 ,  C07K2317/76 ,  C07K2319/30 ,  C07K2319/32 ,  A61K2300/00

Abstract: The present disclosure relates to the use of nucleic acid (e.g., mRNA) combination therapies for the treatment of cancer. The disclosure provides compositions, and methods for their preparation, manufacture, and therapeutic use, wherein those compositions comprise at least two polynucleotides (e.g., mRNAs) in combination wherein the at least two polynucleotides are selected from the group consisting of (i) a polynucleotide encoding an immune response primer (e.g., IL23), (ii) a polynucleotide encoding an immune response co-stimulatory signal (e.g., OX40L), (iii) a polynucleotide encoding a checkpoint inhibitor (e.g., an anti CTLA-4 antibody), and, (iv) a combination thereof. The therapeutic methods disclosed herein comprise, e.g., the administration of a combination therapy disclosed herein for the treatment of cancer, e.g., by reducing the size of a tumor or inhibiting the growth of a tumor, in a subject in need thereof. In some aspects, the combination therapies disclosed herein disclosed are administered intratumorally.