公开(公告)号：US20220265857A1

公开(公告)日：2022-08-25

申请号：US17583674

申请日：2022-01-25

Applicant: ModernaTX,Inc.

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

IPC: A61K48/00 ,  A61K9/127 ,  C12N15/88 ,  A61K31/7115 ,  A61K47/14 ,  A61K47/18 ,  A61K47/54 ,  A61K47/69 ,  A61K47/60 ,  A61K31/713 ,  A61K39/39 ,  A61K47/10 ,  C08G65/332 ,  C08G65/333 ,  C08G65/334 ,  C08G65/335 ,  C12N15/117

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：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：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.

公开(公告)号：US10973917B2

公开(公告)日：2021-04-13

申请号：US16457300

申请日：2019-06-28

Applicant: ModernaTX, Inc.

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

IPC: A61K48/00 ,  A61K39/395 ,  C07K14/54 ,  C07K14/705 ,  C07K16/28 ,  A61K39/39 ,  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：US10646549B2

公开(公告)日：2020-05-12

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: A61K48/00 ,  A61K38/20 ,  A61K9/51 ,  C07K14/54 ,  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：US10406112B2

公开(公告)日：2019-09-10

申请号：US16002376

申请日：2018-06-07

Applicant: ModernaTX, Inc.

Inventor： Paolo Martini ,  Vladimir Presnyak ,  Kerry Benenato

IPC: C12N15/11 ,  A61K9/51 ,  A61K9/127 ,  C12N9/90 ,  A61P3/00 ,  A61P43/00 ,  A61K38/52 ,  A61K48/00 ,  C12N15/52 ,  A61K38/00

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：US20190175517A1

公开(公告)日：2019-06-13

申请号：US16302360

申请日：2017-05-18

Applicant: ModernaTX, Inc.

Inventor： Paolo Martini ,  Stephen Hoge ,  Kerry Benenato ,  Vladimir Presnyak ,  Iain McFadyen ,  Ellalahewage Sathyajith Kumarasinghe ,  Jingsong Cao ,  Lin Tung Guey ,  Staci Sabnis

IPC: A61K9/51 ,  C07K14/47 ,  A61P13/00 ,  A61K9/00

Abstract: The invention relates to mRNA therapy for the treatment of Citrullinemia Type 2 (“CTLN2”). mRNAs for use in the invention, when administered in vivo, encode human Citrin, isoforms thereof, functional fragments thereof, and fusion proteins comprising Citrin. 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 Citrin expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of biomarkers associated with deficient Citrin activity in subjects, namely ammonia and/or triglycerides.

公开(公告)号：US12128113B2

公开(公告)日：2024-10-29

申请号：US16302607

申请日：2017-05-18

Applicant: ModernaTX, Inc.

Inventor： Kerry Benenato ,  Stephen Hoge ,  Paolo Martini ,  Iain Mcfadyen ,  Vladimir Presnyak ,  Ding An ,  Ellalahewage Sathyajith Kumarasinghe

IPC: A61K48/00 ,  A61K9/00 ,  A61K9/51 ,  A61K47/00 ,  A61K47/14 ,  A61K47/16 ,  A61K47/22 ,  A61K47/24 ,  C12N15/88 ,  A61K9/127 ,  A61K47/10 ,  A61K47/28 ,  C07K14/705

CPC classification number: A61K48/0066 ,  A61K9/51 ,  A61K47/14 ,  A61K47/16 ,  A61K47/22 ,  A61K47/24 ,  A61K48/0041 ,  C12N15/88 ,  A61K9/1271 ,  A61K9/5123 ,  A61K47/10 ,  A61K47/28 ,  C07K14/705

Abstract: The invention relates to mRNA therapy for the treatment of Alagille syndrome (ALGS), mRNAs for use in the invention, when administered in vivo, encode JAGGED 1 (JAG1), isoforms thereof functional fragments thereof, and fusion proteins comprising JAG1, 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 JAG1 expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient JAG1 activity in subjects.

公开(公告)号：US20240207444A1

公开(公告)日：2024-06-27

申请号：US18282639

申请日：2022-03-24

Applicant: ModernaTX, Inc.

Inventor： Kerry Benenato ,  Mark Cornebise ,  Edward Hennessy

IPC: A61K48/00 ,  A61K9/127 ,  A61K9/51 ,  C12N9/02

CPC classification number: A61K48/005 ,  A61K9/1271 ,  A61K9/5123 ,  A61K48/0033 ,  A61K48/0075 ,  C12N9/0071 ,  C12Y114/16001

Abstract: This disclosure relates to ionizable amino lipid-based lipid nanoparticles for delivery of mRNA encoding phenylalanine hydroxylase. Lipid nanoparticle/mRNA therapies of the invention increase and/or restore deficient levels of phenylalanine hydroxylase expression and/or activity in subjects and are useful for the treatment of phenylketonuria