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公开(公告)号：US10519455B2
公开(公告)日：2019-12-31
申请号：US16110309
申请日：2018-08-23
申请人： ModernaTX, Inc.
发明人： Paolo Martini , Stephen G. Hoge , Kerry Benenato , Vladimir Presnyak , Iain McFadyen , Ellalahewage Sathyajith Kumarasinghe , Xuling Zhu , Lin Tung Guey , Staci Sabnis
摘要： The invention relates to mRNA therapy for the treatment of Fabry disease. mRNAs for use in the invention, when administered in vivo, encode human the α-galactosidase A (GLA), isoforms thereof, functional fragments thereof, and fusion proteins comprising GLA. 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 GLA expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient GLA activity in subjects, namely Gb3 and lyso-Gb3.
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公开(公告)号：US10335486B2
公开(公告)日：2019-07-02
申请号：US15996146
申请日：2018-06-01
申请人： ModernaTX, Inc.
发明人： Joshua P. Frederick , Susannah Hewitt , Ailin Bai , Stephen G. Hoge , Vladimir Presnyak , Iain McFadyen , Kerry Benenato , Ellalahewage Sathyajith Kumarasinghe
IPC分类号： A61K39/39 , A61K39/395 , C07K14/54 , C07K14/705 , C07K16/28 , A61K45/06 , A61K31/713 , A61K39/00 , A61P35/00
摘要： 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.
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公开(公告)号：US20190192653A1
公开(公告)日：2019-06-27
申请号：US16053839
申请日：2018-08-03
申请人： ModernaTX, Inc.
CPC分类号： A61K39/39 , A61K39/00 , A61K39/0008 , A61K39/001 , A61K39/35 , A61K39/38 , A61K2039/53 , A61K2039/55511 , A61K2039/55516 , A61K2039/572 , C12N15/88
摘要： The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of molecules for tolerizing cellular systems.
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公开(公告)号：US11660341B2
公开(公告)日：2023-05-30
申请号：US17202829
申请日：2021-03-16
申请人： ModernaTX, Inc.
发明人： Joshua P. Frederick , Susannah Hewitt , Ailin Bai , Stephen G. Hoge , Vladimir Presnyak , Iain McFadyen , Kerry Benenato , Ellalahewage Sathyajith Kumarasinghe
IPC分类号： A61K48/00 , A61K39/395 , C07K14/54 , C07K14/705 , C07K16/28 , A61K39/39 , A61K45/06 , A61K31/713 , A61K39/00 , A61P35/00
CPC分类号： 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
摘要： 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.
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公开(公告)号：US11649461B2
公开(公告)日：2023-05-16
申请号：US16570351
申请日：2019-09-13
申请人： ModernaTX, Inc.
发明人： Paolo Martini , Stephen G. Hoge , Kerry Benenato , Vladimir Presnyak , Iain Mcfadyen , Ellalahewage Sathyajith Kumarasinghe , Xuling Zhu , Lin Tung Guey , Staci Sabnis
CPC分类号： C12N15/67 , A61K9/5123 , A61K38/47 , A61P3/00 , C12N9/2465 , C12Y302/01022 , A61K48/00
摘要： The invention relates to mRNA therapy for the treatment of Fabry disease. mRNAs for use in the invention, when administered in vivo, encode human the α-galactosidase A (GLA), isoforms thereof, functional fragments thereof, and fusion proteins comprising GLA. 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 GLA expression and/or activity in subjects. mRNA therapies of the invention further decrease levels of toxic metabolites associated with deficient GLA activity in subjects, namely Gb3 and lyso-Gb3.
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公开(公告)号：US20190185529A1
公开(公告)日：2019-06-20
申请号：US16036170
申请日：2018-07-16
申请人： ModernaTX, Inc.
发明人： Stephen G. Hoge , Tirtha Chakraborty , Joshua P. Frederick , Matthias John , Antonin De Fougerolles
IPC分类号： C07K14/47 , A61K31/711 , C12N15/85 , C12N15/113 , A61K48/00 , A61K31/7105
CPC分类号： C07K14/47 , A61K31/7105 , A61K31/711 , A61K38/00 , A61K48/0058 , C12N15/113 , C12N15/85 , C12N2310/141
摘要： The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of signal-sensor polynucleotides, primary transcripts and mmRNA molecules.
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公开(公告)号：US09597380B2
公开(公告)日：2017-03-21
申请号：US14043927
申请日：2013-10-02
申请人： ModernaTX, Inc.
发明人： Tirtha Chakraborty , Stephane Bancel , Stephen G. Hoge , Atanu Roy , Antonin de Fougerolles , Noubar B. Afeyan
摘要： The invention relates to compositions and methods for the manufacture and optimization of modified mRNA molecules via optimization of their terminal architecture.
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公开(公告)号：US11185510B2
公开(公告)日：2021-11-30
申请号：US16543102
申请日：2019-08-16
申请人： ModernaTX, Inc.
发明人： Joshua P. Frederick , Ailin Bai , Vladimir Presnyak , Stephen G. Hoge , Kerry Benenato , Iain McFadyen , Ellalahewage Sathyajith Kumarasinghe , Susannah Hewitt
IPC分类号： 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
摘要： 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).
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公开(公告)号：US11071716B2
公开(公告)日：2021-07-27
申请号：US17071685
申请日：2020-10-15
申请人： ModernaTX, Inc.
发明人： Joshua Frederick , Ailin Bai , Vladimir Presnyak , Stephen G. Hoge , Kerry Benenato , Iain McFadyen , Ellalahewage Sathyajith Kumarasinghe , Susannah Hewitt
IPC分类号： A61K48/00 , A61K9/51 , 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
摘要： 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).
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公开(公告)号：US09751925B2
公开(公告)日：2017-09-05
申请号：US14960031
申请日：2015-12-04
申请人： ModernaTX, Inc.
发明人： Stephen G. Hoge , William Joseph Issa , Edward John Miracco , Jennifer Nelson , John Reynders , Matthew Stanton
IPC分类号： C07K14/535 , C12P19/34 , C07K14/505 , C12N9/00 , C12N9/02
CPC分类号： C07K14/535 , A61K48/005 , C07K14/505 , C12N9/0069 , C12P19/34 , C12P21/02 , C12Y113/12007
摘要： The present disclosure provides alternative nucleosides, nucleotides, and nucleic acids, and methods of using them. In some aspects, the disclosure provides mRNA wherein the uracil content has been modified and which may be particularly effective for use in therapeutic compositions, because they may benefit from both high expression levels and limited induction of the innate immune response. In some aspects, the disclosure provides methods for the production of pharmaceutical compositions including mRNA without reverse phase chromatography.
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