MRNA therapy for Fabry disease

• US 9,308,281 B2
• Filed: 06/18/2014
• Issued: 04/12/2016
• Est. Priority Date: 06/08/2011
• Status: Active Grant

• Current Assignee: Translate Bio, Inc. (Sanofi )
• Original Assignee: Shire Human Genetic Therapies, Inc. (Shire plc)
• Inventors: Guild, Braydon Charles, DeRosa, Frank, Heartlein, Michael
• Primary Examiner(s): Kelly, Robert M
• Application Number:
  US14/308,546
• Publication Number:
  US 20140294938A1
• Time in Patent Office: 664 Days
• Field of Search: None
• US Class Current: 1/1
• 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 of treating Fabry disease, comprising administering to a human subject in need of treatment an mRNA encoding a human alpha-galactosidase (hGLA) protein such that the hGLA protein is secreted extracellularly after expression and systemically distributed, and such that serum hGLA protein level is increased for at least 72 hours as compared to the baseline serum hGLA level before treatment,

wherein the mRNA is administered via intravenous or pulmonary administration, and

wherein the Fabry disease is treated.

2. The method of claim 1, wherein the mRNA comprises SEQ ID NO:

4.

3. The method of claim 1, wherein the mRNA is encapsulated within a liposome.

4. The method of claim 3, wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

5. The method of claim 1, wherein the mRNA comprises a non-naturally occurring nucleotide.

6. The method of claim 5, wherein the non-naturally occurring nucleotide is pseudouridine.

7. The method of claim 1, wherein the administering to a subject is achieved via intravenous injections.

8. The method of claim 1, wherein the administration of mRNA results in reduction of globotrioasylceramide (Gb3) level in the human subject as compared to the Gb3 level before treatment.