Lipid nanoparticle compositions and methods for MRNA delivery

• US 10,238,754 B2
• Filed: 04/07/2017
• Issued: 03/26/2019
• Est. Priority Date: 06/08/2011
• Status: Active Grant

• Current Assignee: Translate Bio, Inc. (Sanofi )
• Original Assignee: Translate Bio, Inc. (Sanofi )
• Inventors: Guild, Braydon Charles, DeRosa, Frank, Heartlein, Michael
• Primary Examiner(s): Kelly, Robert M
• Application Number:
  US15/482,117
• Publication Number:
  US 20170239371A1
• Time in Patent Office: 718 Days
• Field of Search: None
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 38/47 acting on glycosyl compounds (3.2), e.g. cellulases, lactases
• CPC Class Codes: A61K 38/4846 Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)
• CPC Class Codes: A61K 38/57 from animals; from humans A61K38/553, A61K38/556 take precedence
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 48/0008 characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61K 48/0091 Purification or manufacturing processes for gene therapy compositions
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/1272 with substantial amounts of non-phosphatidyl, i.e. non-acylglycerophosphate, surfactants as bilayer-forming substances, e.g. cationic lipids with cholesterol as the only non-phosphatidyl surfactant A61K9/127; lipids as modifying agent A61K47/543
• CPC Class Codes: A61K 9/5123 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C07K 14/505 Erythropoietin [EPO]
• CPC Class Codes: C07K 14/8125 Alpha-1-antitrypsin
• CPC Class Codes: C12N 15/52 : Genes encoding for enzymes or proenzymes
• CPC Class Codes: C12N 15/85 : for animal cells
• CPC Class Codes: C12N 9/2465 : acting on alpha-galactose-glycoside bonds, e.g. alpha-galactosidase (3.2.1.22)
• CPC Class Codes: C12N 9/644 : Coagulation factor IXa (3.4.21.22)
• CPC Class Codes: C12Y 302/01022 : Alpha-galactosidase (3.2.1.22)
• CPC Class Codes: C12Y 304/21022 : Coagulation factor IXa (3.4.21.22)

Abstract

Disclosed herein are compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies.

Claims

1. A method for delivery of messenger RNA (mRNA) for in vivo production of a protein, comprising administering to a human, a composition comprising an mRNA that encodes a protein or a peptide, wherein the mRNA is encapsulated within a lipid nanoparticle and wherein the administering of the composition results in expression of the protein or peptide encoded by the mRNA that is detectable in serum at least 72 hours after administration, wherein the lipid nanoparticle comprises one or more PEG-modified lipids.

2. The method of claim 1, wherein the lipid nanoparticle has a size of less than about 100 nm.

3. The method of claim 1, wherein the mRNA comprises at least one modification that enhances the stability of the mRNA relative to its unmodified counterpart.

4. The method of claim 3, wherein the modification comprises a modified nucleotide.

5. The method of claim 4, wherein modified nucleotide is pseudouridine.

6. The method of claim 3, wherein the mRNA comprises a 5′

untranslated region.

7. The method of claim 3, wherein the mRNA comprises a 3′

untranslated region.

8. The method of claim 3, wherein the mRNA comprises a cap structure.

9. The method of claim 3, wherein the mRNA comprises a poly A tail.

10. The method of claim 1, wherein the mRNA is unmodified.

11. The method of claim 1, wherein the composition is administered by intravenous injection.

12. The method of claim 1, wherein the composition is administered by pulmonary delivery.

13. The method of claim 1, wherein the composition is administered by intramuscular delivery.