Modified polynucleotides for the production of proteins
First Claim
Patent Images
1. An mRNA encoding SEQ ID NO:
- 13267, wherein said mRNA comprises a coding region, said coding region having at least 80% identity to SEQ ID NO;
22033.
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Abstract
The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.
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Citations
14 Claims
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1. An mRNA encoding SEQ ID NO:
- 13267, wherein said mRNA comprises a coding region, said coding region having at least 80% identity to SEQ ID NO;
22033. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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2. The mRNA of claim 1, wherein mRNA comprises a 3′
- tailing sequence of linked nucleosides and wherein the 3′
tailing sequence of linked nucleosides is selected from the group consisting of a poly-A tail of approximately 160 nucleotides and a polyA-G quartet.
- tailing sequence of linked nucleosides and wherein the 3′
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3. The mRNA of claim 1 which is purified.
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4. The mRNA of claim 1, wherein the mRNA comprises at least one 5′
- terminal cap and wherein the at least one 5′
terminal cap is selected from the group consisting of Cap0, Cap1, ARCA, inosine, N1-methyl-guanosine, 2′
fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino-guanosine, LNA-guanosine, and 2-azido-guanosine.
- terminal cap and wherein the at least one 5′
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5. The mRNA of claim 1, wherein the mRNA comprises a 5′
- untranslated region (UTR) at the 5′
terminus of the coding region and a 3′
UTR at the 3′
terminus of the coding region.
- untranslated region (UTR) at the 5′
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6. The mRNA of claim 5, wherein the 5′
- UTR and the 3′
UTR are not derived from the same species.
- UTR and the 3′
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7. The mRNA of claim 5, wherein at least one of the 5′
- UTR or the 3′
UTR is not derived from beta-globin.
- UTR or the 3′
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8. The mRNA of claim 1, wherein the coding region is selected from the group consisting of SEQ ID NO:
- 22033 and 39565.
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9. A pharmaceutical composition comprising the mRNA of claim 1.
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10. The pharmaceutical composition of claim 9, wherein the pharmaceutical composition comprises a pharmaceutically acceptable excipient, wherein the pharmaceutically acceptable excipient is selected from a solvent, aqueous solvent, non-aqueous solvent, dispersion media, diluent, dispersion, suspension aid, surface active agent, isotonic agent, thickening or emulsifying agent, preservative, lipid, lipidoids liposome, lipid nanoparticle, core-shell nanoparticles, polymer, lipoplex peptide, protein, cell, hyaluronidase, and mixtures thereof.
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11. The pharmaceutical composition of claim 10, where the pharmaceutical composition comprises a lipid and wherein said lipid is selected from DLin-DMA, DLin-K-DMA, DLin-KC2-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DODMA, DSDMA, DLenDMA, reLNPs, PLGA and PEGylated lipids and mixtures thereof.
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12. A method of producing a polypeptide of interest in a mammalian cell, tissue or organism comprising administering to said cell, tissue or organism the pharmaceutical composition of claim 9.
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13. The method of claim 12, wherein the mRNA is formulated.
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14. The method of claim 13, wherein the formulation comprises a lipid which is selected from one of DLin-DMA, DLin-K-DMA, DLin-KC2-DMA, 98N12-5, C12-200, DLin-MC3-DMA, DODMA, DSDMA, DLenDMA, reLNPs, PLGA, PEGylated lipids and mixtures or combinations thereof.
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2. The mRNA of claim 1, wherein mRNA comprises a 3′
- 13267, wherein said mRNA comprises a coding region, said coding region having at least 80% identity to SEQ ID NO;
Specification
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Current AssigneeModerna Therapeutics, Inc. (Moderna, Inc.)
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Original AssigneeModerna Therapeutics, Inc. (Moderna, Inc.)
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InventorsBancel, Stephane, Chakraborty, Tirtha, de Fougerolles, Antonin, Elbashir, Sayda M., John, Matthias, Roy, Atanu, Whoriskey, Susan, Wood, Kristy M., Hatala, Paul, Schrum, Jason P., Ejebe, Kenechi, Ellsworth, Jeff Lynn, Guild, Justin
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Primary Examiner(s)Gonzalez, Antonio Galisteo
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Application NumberUS14/390,100Publication NumberTime in Patent Office1,067 DaysField of SearchNoneUS Class Current1/1CPC Class CodesA61K 31/7088 Compounds having three or m...A61K 31/7115 Nucleic acids or oligonucle...A61K 38/00 Medicinal preparations cont...A61K 38/17 from animals; from humans e...A61K 38/1767 from invertebratesA61K 38/177 Receptors; Cell surface ant...A61K 38/1816 Erythropoietin [EPO]A61K 38/1866 Vascular endothelial growth...A61K 38/1891 Angiogenesic factors; Angio...A61K 38/191 Tumor necrosis factors [TNF...A61K 38/193 Colony stimulating factors ...A61K 38/212 IFN-alphaA61K 38/215 IFN-betaA61K 38/36 Blood coagulation or fibrin...A61K 38/363 FibrinogenA61K 38/44 Oxidoreductases (1)A61K 38/45 Transferases (2)A61K 38/4833 Thrombin (3.4.21.5)A61K 38/4846 Factor VII (3.4.21.21); Fac...A61K 39/3955 against proteinaceous mater...A61K 47/10 : Alcohols; Phenols; Salts th...A61K 47/34 : Macromolecular compounds ob...A61K 47/54 : the modifying agent being a...A61K 47/542 : Carboxylic acids, e.g. a fa...A61K 47/543 : Lipids, e.g. triglycerides;...A61K 48/00 : Medicinal preparations cont...A61K 48/0033 : the non-active part being n...A61K 48/005 : characterised by an aspect ...A61K 48/0066 : Manipulation of the nucleic...A61K 48/0075 : characterised by an aspect ...A61K 9/0019 : Injectable compositions; In...A61K 9/1271 : Non-conventional liposomes,...A61K 9/1272 : with substantial amounts of...A61K 9/1277 : Processes for preparing; Pr...A61K 9/14 : Particulate form, e.g. powd...A61K 9/145 : with organic compoundsA61K 9/5031 : obtained otherwise than by ...A61K 9/5123 : Organic compounds, e.g. fat...A61K 9/5146 : obtained otherwise than by ...A61K 9/5153 : Polyesters, e.g. poly(lacti...C07K 14/005 : from virusesC07K 14/435 : from animals; from humansC07K 14/47 : from mammalsC07K 14/4705 : stimulating, promoting or a...C07K 14/4713 : Autoimmune diseases, e.g. I...C07K 14/475 : Growth factors; Growth regu...C07K 14/485 : Epidermal growth factor [EG...C07K 14/505 : Erythropoietin [EPO]C07K 14/515 : Angiogenesic factors; Angio...C07K 14/525 : Tumour necrosis factor [TNF]C07K 14/535 : Granulocyte CSF; Granulocyt...C07K 14/56 : IFN-alphaC07K 14/565 : IFN-betaC07K 14/62 : InsulinsC07K 14/705 : Receptors; Cell surface ant...C07K 14/745 : Blood coagulation or fibrin...C07K 14/75 : FibrinogenC07K 16/00 : Immunoglobulins [IGs], e.g....C07K 16/2887 : against CD20C07K 16/32 : against translation product...C07K 19/00 : Hybrid peptides , i.e. pept...C12N 15/11 : DNA or RNA fragments; Modif...C12N 15/52 : Genes encoding for enzymes ...C12N 15/67 : General methods for enhanci...C12N 15/85 : for animal cellsC12N 15/87 : Introduction of foreign gen...C12N 15/88 : using microencapsulation, e...C12N 2840/00 : Vectors comprising a specia...C12N 2840/85 : mammalianC12N 9/0069 : acting on single donors wit...C12N 9/1051 : Hexosyltransferases (2.4.1)C12N 9/16 : acting on ester bonds (3.1)C12N 9/2402 : hydrolysing O- and S- glyco...C12N 9/2445 : Beta-glucosidase (3.2.1.21)C12N 9/644 : Coagulation factor IXa (3.4...C12N 9/6451 : Coagulation factor XIIa (3....C12N 9/88 : Lyases (4.)C12N 9/93 : Ligases (6)C12P 13/04 : Alpha- or beta- amino acids...C12P 21/00 : Preparation of peptides or ...C12P 21/005 : Glycopeptides, glycoproteinsC12Y 113/12007 : Photinus-luciferin 4-monoox...C12Y 304/21005 : Thrombin (3.4.21.5)C12Y 304/21022 : Coagulation factor IXa (3.4...C12Y 603/02019 : Ubiquitin-protein ligase (6...