MRNA therapy for phenylketonuria

• US 10,208,295 B2
• Filed: 11/11/2016
• Issued: 02/19/2019
• Est. Priority Date: 10/22/2013
• Status: Active Grant

• Current Assignee: Translate Bio, Inc. (Sanofi )
• Original Assignee: Translate Bio, Inc. (Sanofi )
• Inventors: DeRosa, Frank, Heartlein, Michael, Dias, Anusha
• Primary Examiner(s): Leavitt, Maria G
• Application Number:
  US15/349,720
• Publication Number:
  US 20170073648A1
• Time in Patent Office: 830 Days
• Field of Search: None
• CPC Class Codes: A61K 38/44 Oxidoreductases (1)
• 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 48/0033 the non-active part being non-polymeric
• CPC Class Codes: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• 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: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: C12N 9/0071 acting on paired donors with incorporation of molecular oxygen (1.14)
• CPC Class Codes: C12Y 114/16001 Phenylalanine 4-monooxygenase (1.14.16.1)

Abstract

The present invention provides, among other things, methods of treating phenylketonuria (PKU), including administering to a subject in need of treatment a composition comprising an mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose and an administration interval such that at least one symptom or feature of PKU is reduced in intensity, severity, or frequency or has delayed in onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids.

Claims

1. A composition for treating phenylketonuria (PKU), comprising an mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose amount encapsulated within a liposome,

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 and wherein the liposome has a size less than 100 nm,

wherein serum phenylalanine levels are reduced as compared to baseline serum phenylalanine levels before treatment,

wherein the mRNA comprises SEQ ID NO:

3.

2. A composition for treating phenylketonuria (PKU), comprising an mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose amount encapsulated within a liposome, wherein the mRNA comprises SEQ ID NO:

3, and

further 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 and wherein the liposome has a size less than 100 nm.

3. A composition for treating phenylketonuria (PKU), comprising an mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose amount encapsulated within a liposome,

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 and wherein the liposome has a size less than 100 nm,

wherein serum phenylalanine levels are reduced as compared to baseline serum phenylalanine levels before treatment,

wherein the mRNA encoding phenylalanine hydroxylase (PAH) has a coding sequence 100% identical to SEQ ID NO:

3.