公开(公告)号：US10335486B2

公开(公告)日：2019-07-02

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: A61K39/39 ,  A61K39/395 ,  C07K14/54 ,  C07K14/705 ,  C07K16/28 ,  A61K45/06 ,  A61K31/713 ,  A61K39/00 ,  A61P35/00

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.

公开(公告)号：US20180271795A1

公开(公告)日：2018-09-27

申请号：US16002376

申请日：2018-06-07

Applicant: ModernaTX, Inc.

Inventor： Paolo Martini ,  Vladimir Presnyak

IPC: A61K9/51 ,  A61P3/00 ,  C12N9/90

CPC classification number: A61K9/5123 ,  A61K9/1272 ,  A61K38/00 ,  A61K38/52 ,  A61K48/005 ,  A61P3/00 ,  A61P43/00 ,  C12N9/90 ,  C12N15/52 ,  C12Y504/99002

Abstract: The disclosure relates to polynucleotides comprising an open reading frame of linked nucleosides encoding human methylmalonyl-CoA mutase precursor, human methylmalonyl-CoA mutase (MCM) mature form, or functional fragments thereof. In some embodiments, the disclosure includes methods of treating methylmalonic acidemia in a subject in need thereof comprising administering an mRNA encoding an MCM polypeptide.

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：US20240269248A1

公开(公告)日：2024-08-15

申请号：US18560498

申请日：2022-05-19

Applicant: ModernaTX, Inc.

Inventor： Husain Attarwala ,  Kimberly Ann Coughlan ,  Ruchi Jain ,  Matthew Lumley ,  Vladimir Presnyak

IPC: A61K38/52 ,  A61K9/00 ,  A61K9/51 ,  A61K31/167 ,  A61K48/00 ,  A61P3/00

CPC classification number: A61K38/52 ,  A61K9/0019 ,  A61K9/5123 ,  A61K31/167 ,  A61K48/0033 ,  A61P3/00

Abstract: This disclosure relates to mRNA therapy for the treatment of methylmalonic acidemia (MMA). mRNAs for use in the invention, when administered in vivo, encode methylmalonyl-CoA mutase (MUT). mRNA therapies of the disclosure increase and/or restore deficient levels of MUT expression and/or activity in subjects.

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.

公开(公告)号：US11485972B2

公开(公告)日：2022-11-01

申请号：US16614245

申请日：2018-05-18

Applicant: ModernaTX, Inc.

Inventor： Melissa J. Moore ,  Caroline Köhrer ,  Ruchi Jain ,  Vladimir Presnyak

IPC: C07H21/02 ,  C07H21/04 ,  C12N15/11 ,  A61K47/69 ,  C12N15/85 ,  C12N15/88

Abstract: The present disclosure provides messenger RNAs (mRNAs) having chemical and/or structural modifications, including RNA elements and/or modified nucleotides, which provide a desired translational regulatory activity to the mRNA.

公开(公告)号：US11344504B1

公开(公告)日：2022-05-31

申请号：US17352904

申请日：2021-06-21

Applicant: ModernaTX, Inc.

Inventor： Joshua P. Frederick ,  Ailin Bai ,  Vladimir Presnyak ,  Stephen G. Hoge ,  Kerry Benenato ,  Iain McFadyen ,  Ellalahewage Sathyajith Kumarasinghe ,  Susannah Hewitt

IPC: A61K38/20 ,  A61K9/51 ,  A61K48/00 ,  A61K38/17 ,  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：US11311602B2

公开(公告)日：2022-04-26

申请号：US17308686

申请日：2021-05-05

Applicant: ModernaTX, Inc.

Inventor： Joshua Frederick ,  Susannah Hewitt ,  Ailin Bai ,  Stephen Hoge ,  Vladimir Presnyak ,  Iain 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.

公开(公告)号：US20220054653A1

公开(公告)日：2022-02-24

申请号：US17276112

申请日：2019-09-13

Applicant: ModernaTX, Inc.

Inventor： Paolo Martini ,  Vladimir Presnyak ,  Jingsong CAO

IPC: A61K48/00 ,  A61K9/51 ,  C07K14/705 ,  A61P1/16

Abstract: The present disclosure provides compositions of nucleic acids relating to biliary epithelial transporters. For example, the present disclosure relates to nucleic acids capable of regulating the biliary secretion of phospholipids, including phosphatidylcholine, e.g., those encoded by ATP binding cassette subfamily B member 4 (ABCB4) or a biologically active fragment thereof, in a target cell. In a preferred embodiment, the present disclosure provides compositions comprising modified mRNA encoding ABCB4 formulated in a lipid nanoparticle (LNP) carrier and derivative constructs, which are useful for treating or preventing progressive familial intrahepatic cholestasis type 3 (PFIC3).

公开(公告)号：US11000573B2

公开(公告)日：2021-05-11

申请号：US16842300

申请日：2020-04-07

Applicant: ModernaTX, Inc.

Inventor： Joshua Frederick ,  Susannah Hewitt ,  Ailin Bai ,  Stephen Hoge ,  Vladimir Presnyak ,  Iain 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.