公开(公告)号：US11660341B2

公开(公告)日：2023-05-30

申请号：US17202829

申请日：2021-03-16

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

CPC classification number: A61K39/39558 ,  A61K31/713 ,  A61K39/0011 ,  A61K39/39 ,  A61K45/06 ,  A61K48/005 ,  C07K14/54 ,  C07K14/5434 ,  C07K14/5443 ,  C07K14/705 ,  C07K14/70503 ,  C07K14/70532 ,  C07K14/70575 ,  C07K14/70596 ,  C07K16/2818 ,  A61K2039/505 ,  A61K2039/51 ,  A61K2039/53 ,  A61K2039/585 ,  A61P35/00 ,  C07K2317/76 ,  C07K2319/30 ,  C07K2319/32 ,  A61K31/713 ,  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.

公开(公告)号：US11001861B2

公开(公告)日：2021-05-11

申请号：US16302341

申请日：2017-05-18

Applicant: ModernaTX, Inc.

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

IPC: C12N15/88 ,  A61K9/51 ,  B82Y5/00 ,  C07K14/14 ,  C12N9/12 ,  G01N33/68 ,  A61K48/00

Abstract: The invention relates to mRNA therapy for the treatment of galactosemia type 1 (Gal-1). mRNAs for use in the invention, when administered in vivo, encode human galactose-1-phosphate uridylyltransferase (GALT), isoforms thereof, functional fragments thereof, and fusion proteins comprising GALT. 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 GALT expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient GALT activity in subjects, namely galactose-1-phosphate (Gal-1-P).

公开(公告)号：US10406113B2

公开(公告)日：2019-09-10

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: 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：US10172808B2

公开(公告)日：2019-01-08

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: A61K48/00 ,  A61K31/7115 ,  A61K9/51 ,  A61K38/20 ,  A61K38/17 ,  C07K14/54 ,  C07K14/705 ,  A61K39/395 ,  A61K9/00 ,  A61P35/00 ,  A61K39/00

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：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：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：US20210217484A1

公开(公告)日：2021-07-15

申请号：US17145164

申请日：2021-01-08

Applicant: ModernaTX, Inc.

Inventor： Andrew Giessel ,  Athanasios Dousis ,  Iain McFadyen

IPC: G16B5/20 ,  G16B20/20 ,  G16B40/00

Abstract: Techniques for manufacturing a variant of a target protein. The techniques may include accessing a latent variable statistical model (LVSM) configured to generate output indicating one or more biological sequences corresponding to one or more variants of the target protein and using the LVSM to generate a first output indicating a first biological sequence associated with a first variant of the target protein. The techniques further include manufacturing, using the first biological sequence, a first biological molecule to produce the first variant of the target protein.

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.