公开(公告)号：US20190125839A1

公开(公告)日：2019-05-02

申请号：US16192274

申请日：2018-11-15

Applicant: ModernaTX, Inc.

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

IPC: A61K38/20 ,  A61K9/51 ,  A61P35/00 ,  A61K9/00

Abstract: The present disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human interleukin-12 (IL12), functional fragments thereof, and fusion proteins comprising IL12. In some embodiments, the open reading frame is sequence-optimized. In particular embodiments, the disclosure provides sequence-optimized polynucleotides comprising nucleotides encoding the polypeptide sequence of human IL12, or sequences having high sequence identity with those sequence optimized polynucleotides.

公开(公告)号：US20170362627A1

公开(公告)日：2017-12-21

申请号：US15525826

申请日：2015-11-04

Applicant: MODERNATX, INC.

Inventor： John van Wicheren REYNDERS, III ,  Tirtha CHAKRABORTY ,  Stephen HOGE ,  Iain James MCFADYEN

IPC: C12P21/02 ,  A61K38/02 ,  C07K14/00

CPC classification number: C12P21/02 ,  A61K38/02 ,  C07K14/00 ,  C07K2319/00

Abstract: The present disclosure provides multiparametric codon optimization methods to improve at least a property in a candidate nucleic acid sequence. Such parameters include improving nucleic acid stability (e.g., mRNA stability), increasing translation efficacy in the target tissue, reducing the number of truncated proteins expressed, improving the folding or prevent misfolding of the expressed proteins, reducing toxicity of the expressed products, reducing cell death caused by the expressed products, and increasing or decreasing protein aggregation. After such optimization, the resulting optimized nucleic acid sequence has at least one optimized property with respect to the candidate nucleic acid sequence.

公开(公告)号：US20230146324A1

公开(公告)日：2023-05-11

申请号：US17683235

申请日：2022-02-28

Applicant: ModernaTX, Inc.

Inventor： John van Wicheren REYNDERS, III ,  Tirtha CHAKRABORTY ,  Stephen HOGE ,  Iain James MCFADYEN

IPC: C12P21/02 ,  A61K31/7088 ,  A61K38/02

CPC classification number: C12P21/02 ,  A61K31/7088 ,  A61K38/02 ,  C07K14/00

Abstract: The present disclosure provides multiparametric codon optimization methods to improve at least a property in a candidate nucleic acid sequence, for example the translation efficacy of a therapeutic mRNA.

公开(公告)号：US20230026381A1

公开(公告)日：2023-01-26

申请号：US17930369

申请日：2022-09-07

Applicant: ModernaTX, Inc.

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

IPC: A61K9/51 ,  A61K48/00 ,  A61K38/17 ,  A61K38/20 ,  A61K9/00 ,  A61K39/39 ,  A61K45/06 ,  A61K9/127 ,  C07K14/54 ,  C07K14/545 ,  C07K14/705 ,  A61K31/7088 ,  A61K31/7115 ,  A61P35/00 ,  A61K39/395

Abstract: The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36γ (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).

公开(公告)号：US20220265774A1

公开(公告)日：2022-08-25

申请号：US17721583

申请日：2022-04-15

Applicant: ModernaTX, Inc.

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

IPC: A61K38/20 ,  A61K9/51 ,  C07K14/54 ,  A61K31/7088 ,  A61K31/7115 ,  A61K48/00 ,  C12N15/62 ,  A61P35/00 ,  A61K9/00

Abstract: The present disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human interleukin-12 (IL12), functional fragments thereof, and fusion proteins comprising IL12. In some embodiments, the open reading frame is sequence-optimized. In particular embodiments, the disclosure provides sequence-optimized polynucleotides comprising nucleotides encoding the polypeptide sequence of human IL12, or sequences having high sequence identity with those sequence optimized polynucleotides.

公开(公告)号：US20210260097A1

公开(公告)日：2021-08-26

申请号：US17036374

申请日：2020-09-29

Applicant: ModernaTX, Inc.

Inventor： Stephen HOGE ,  Tirtha CHAKRABORTY ,  Gilles BESIN ,  Ruchi JAIN

IPC: A61K31/7115 ,  C12N15/67 ,  A61K9/00 ,  A61K9/127 ,  C12N15/113

Abstract: The disclosure features methods of reducing or inhibiting an anti-drug antibody response in a subject, as well as methods of reducing or inhibiting unwanted immune cell activation in a subject to be treated with a messenger RNA (mRNA), comprising administering to the subject a mRNA, e.g., a chemically modified messenger RNA (mmRNA), encoding a polypeptide of interest, wherein the mRNA comprises at least one microRNA (miR) binding site for a miR expressed in immune cells, such as miR-126 binding site and/or miR-142 binding site, such that an anti-drug antibody response to the polypeptide or interest, or unwanted immune cell activation (e.g., B cell activation, cytokine secretion), is reduced or inhibited in the subject. The disclosure further provides therapeutic treatment regimens designed to reduce or inhibit ADA or unwanted immune cell activation (e.g., B cell activation, cytokine secretion) in a subject being treated with mRNA-based therapeutics.

公开(公告)号：US20190298657A1

公开(公告)日：2019-10-03

申请号：US16302298

申请日：2017-05-18

Applicant: MODERNATX, INC.

Inventor： Paolo MARTINI ,  Stephen HOGE ,  Kerry BENENATO ,  Vladimir PRESNYAK ,  Iain McFADYEN ,  Ellalahewage Sathyajith KUMARASINGHE ,  Evan Lockwood RACHLIN ,  Staci SABNIS

IPC: A61K9/51 ,  C12N9/02 ,  A61K48/00

Abstract: The invention relates to mRNA therapy for the treatment of VLCADD. mRNAs for use in the invention, when administered in vivo, encode human acyl-CoA dehydrogenase, very longchain (ACADVL), isoforms thereof, functional fragments thereof, and fusion proteins comprising ACADVL. 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 ACADVL expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient ACADVL activity in subjects, namely acylcarnitine and acylcarnitine metabolites.

公开(公告)号：US20190105280A1

公开(公告)日：2019-04-11

申请号：US16219418

申请日：2018-12-13

Applicant: ModernaTX, Inc.

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

IPC: A61K9/51 ,  A61K9/00 ,  C07K14/54 ,  A61K38/17 ,  A61K38/20 ,  C07K14/705 ,  A61P35/00 ,  A61K39/395

Abstract: The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36γ (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).

公开(公告)号：US20180318229A1

公开(公告)日：2018-11-08

申请号：US15995889

申请日：2018-06-01

Applicant: ModernaTX, Inc.

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

IPC: A61K9/51 ,  A61P35/00 ,  A61K38/20 ,  A61K38/17 ,  C07K14/54 ,  C07K14/705 ,  A61K39/395 ,  A61K9/00

CPC classification number: A61K9/5123 ,  A61K9/00 ,  A61K9/0019 ,  A61K9/1272 ,  A61K9/5146 ,  A61K38/177 ,  A61K38/1774 ,  A61K38/20 ,  A61K38/2006 ,  A61K38/208 ,  A61K38/2086 ,  A61K39/39 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  A61K2039/51 ,  A61K2039/53 ,  A61K2039/54 ,  A61K2039/545 ,  A61K2039/585 ,  A61P35/00 ,  B82Y5/00 ,  C07K14/54 ,  C07K14/5434 ,  C07K14/5443 ,  C07K14/5446 ,  C07K14/545 ,  C07K14/70575 ,  C07K2319/00 ,  C12N15/88 ,  A61K2300/00

Abstract: The disclosure relates to compositions and methods for the preparation, manufacture and therapeutic use of combinations of immunomodulatory polynucleotides (e.g., mRNAs) encoding an immune response primer polypeptide (e.g., an interleukin 23 (IL-23) polypeptide or an interleukin 36γ (IL-36-gamma) polypeptide), and an immune response co-stimulatory signal polypeptide (e.g., an OX40L polypeptide).

公开(公告)号：US20180256628A1

公开(公告)日：2018-09-13

申请号：US15761220

申请日：2016-10-05

Applicant: ModernaTX, Inc.

Inventor： Stephen HOGE ,  Tirtha CHAKRABORTY ,  Gilles BESIN ,  Ruchi JAIN

IPC: A61K31/7115 ,  C12N15/67 ,  A61K9/127 ,  A61K9/00 ,  C12N15/113

CPC classification number: A61K31/7115 ,  A61K9/0019 ,  A61K9/127 ,  C12N15/113 ,  C12N15/67 ,  C12N2310/141 ,  C12N2800/107 ,  C12N2800/22

Abstract: The disclosure features methods of reducing or inhibiting an anti-drug antibody response in a subject, as well as methods of reducing or inhibiting unwanted immune cell activation in a subject to be treated with a messenger RNA (mRNA), comprising administering to the subject a mRNA, e.g., a chemically modified messenger RNA (mmRNA), encoding a polypeptide of interest, wherein the mRNA comprises at least one microRNA (miR) binding site for a miR expressed in immune cells, such as miR-126 binding site and/or miR-142 binding site, such that an anti-drug antibody response to the polypeptide or interest, or unwanted immune cell activation (e.g., B cell activation, cytokine secretion), is reduced or inhibited in the subject. The disclosure further provides therapeutic treatment regimens designed to reduce or inhibit AD A or unwanted immune cell activation (e.g., B cell activation, cytokine secretion) in a subject being treated with mRNA-based therapeutics.