公开(公告)号：US11596609B2

公开(公告)日：2023-03-07

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 ,  A61K39/00 ,  B82Y5/00 ,  C12N15/88

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：US11590157B2

公开(公告)日：2023-02-28

申请号：US17036374

申请日：2020-09-29

Applicant: ModernaTX, Inc.

Inventor： Stephen Hoge ,  Tirtha Chakraborty ,  Gilles Besin ,  Ruchi Jain

IPC: C07H21/02 ,  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：US10322091B2

公开(公告)日：2019-06-18

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: A61K48/00 ,  A61K9/51 ,  A61K38/17 ,  A61K38/20 ,  A61K9/00 ,  A61K39/39 ,  A61K45/06 ,  A61K9/127 ,  C07K14/54 ,  C07K14/545 ,  C07K14/705 ,  A61P35/00 ,  A61K39/395 ,  A61K39/00 ,  B82Y5/00 ,  C12N15/88

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：US20190105281A1

公开(公告)日：2019-04-11

申请号：US16222155

申请日：2018-12-17

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

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 ,  A61K48/00 ,  A61K48/005 ,  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：US20180363019A1

公开(公告)日：2018-12-20

申请号：US16001786

申请日：2018-06-06

Applicant: ModernaTX, Inc.

Inventor： Stephen Hoge ,  William Issa ,  Edward J. Miracco ,  Jennifer Nelson ,  Amy E. Rabideau ,  Gabor Butora

IPC: C12P19/34

Abstract: The invention relates to improved RNA compositions for use in therapeutic applications. The RNA compositions are particularly suited for use in human therapeutic application (e.g., in RNA therapeutics). The RNA compositions are made by inproved processes, in particular, improved in vitro-transcription (IVT) processes. The invention also relates to methods for producing and purifying RNA (e.g, therapeutic RNAs), as well as methods for using the RNA compositions and therapeutic applications thereof.

公开(公告)号：US20180147298A1

公开(公告)日：2018-05-31

申请号：US15674107

申请日：2017-08-10

Applicant: ModernaTX, Inc.

Inventor： Gilles Besin ,  Stephen Hoge ,  Joseph Senn ,  Kerry Benenato ,  Staci Sabnis

IPC: A61K48/00 ,  A61K47/69 ,  A61K47/60 ,  A61K47/54

Abstract: This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins. These compositions are not subject to accelerated blood clearance and they have an improved toxicity profile in vivo.

公开(公告)号：US12233084B2

公开(公告)日：2025-02-25

申请号：US17523060

申请日：2021-11-10

Applicant: ModernaTX, Inc.

Inventor： Stephen Hoge ,  William Issa ,  Edward J. Miracco ,  Jennifer Nelson ,  Amy E. Rabideau ,  Gabor Butora

IPC: A61K31/7105 ,  A61P31/04 ,  A61P31/12 ,  A61P33/00 ,  A61P35/00 ,  C07K14/505 ,  C12N15/10 ,  C12P19/34 ,  G01N33/68

Abstract: The invention relates to improved RNA compositions for use in therapeutic applications. The RNA compositions are particularly suited for use in human therapeutic application (e.g., in RNA therapeutics). The RNA compositions are made by inproved processes, in particular, improved in vitro-transcription (IVT) processes. The invention also relates to methods for producing and purifying RNA (e.g, therapeutic RNAs), as well as methods for using the RNA compositions and therapeutic applications thereof.

公开(公告)号：US12123030B2

公开(公告)日：2024-10-22

申请号：US16302368

申请日：2017-05-18

Applicant: ModernaTX, Inc.

Inventor： Kerry Benenato ,  Stephen Hoge ,  Paolo Martini ,  Iain McFadyen ,  Vladimir Presnyak ,  Ellalahewage Sathyajith Kumarasinghe

IPC: A61K48/00 ,  A61K9/127 ,  A61K9/51 ,  A61K47/14 ,  C12N9/20 ,  B82Y5/00 ,  B82Y30/00

CPC classification number: C12N9/20 ,  A61K9/1274 ,  A61K9/5123 ,  A61K47/14 ,  B82Y5/00 ,  B82Y30/00 ,  C12Y301/01034

Abstract: The invention relates to mRNA therapy for the treatment of hyperlipidemia. mRNAs for use in the invention, when administered in vivo, encode human lipoprotein lipase (LPL), isoforms thereof, functional fragments thereof, and fusion proteins comprising LPL. 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 LPL expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of triglycerides associated with deficient LPL activity in subjects.

公开(公告)号：US11786607B2

公开(公告)日：2023-10-17

申请号：US16623069

申请日：2018-06-15

Applicant: ModernaTX, Inc.

Inventor： Stephen Hoge ,  Joseph Schariter ,  Charles Bowerman ,  Michael H. Smith ,  Yan Xia

IPC: A61K47/69 ,  A61K47/54 ,  A61K31/7105

CPC classification number: A61K47/6931 ,  A61K31/7105 ,  A61K47/543

Abstract: This disclosure provides improved lipid-based compositions, including lipid nanoparticle compositions, and methods of use thereof for delivering agents in vivo including nucleic acids and proteins.

公开(公告)号：US11571463B2

公开(公告)日：2023-02-07

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: A61K48/00 ,  A61K38/20 ,  A61K9/51 ,  C07K14/54 ,  A61K31/7088 ,  A61K31/7115 ,  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.