# US 12,569,572 B2 · Messenger RNA therapy for the treatment of Friedreich's ataxia

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- Number: US 12,569,572 B2
- Document ID: US12569572B2
- Status: Granted
- Kind: B2
- Application number: 17/016,860
- Filed: 2020-09-10
- Published: 2021-06-24
- Granted: 2026-03-10
- Earliest claimed: 2017-06-19
- Assignees: Translate Bio, Inc.
- Applicants: Translate Bio, Inc.
- Inventors: Michael Heartlein; Frank DeRosa; Jonathan Cherry; Paula Lewis; Shrirang Karve; Zarna Patel; Darshan Parekh; Susan Wood; Chi-Sung Chiu; Caroline J. Woo
- Web page: https://patentgrep.com/patent/US12569572B2

## CPC

- A61K 48/005: {characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered}
- 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)}
- A61K 9/0087: {Galenical forms not covered by A61K9/02 - A61K9/7023}
- A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)}
- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 38/02: Peptides of undefined number of amino acids; Derivatives thereof
- A61K 38/1709: {from mammals}
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 15/52: Genes encoding for enzymes or proenzymes
- C12N 15/62: DNA sequences coding for fusion proteins
- C12N 15/88: using microencapsulation, e.g. using {amphiphile} liposome vesicle
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention provides methods and compositions of treating Friedreich's ataxia (FRDA) based on administering an mRNA encoding a frataxin protein.

## Claims

### Claim 1

A pharmaceutical composition for treating Friedreich's ataxia (FRDA), comprising an mRNA encoding a human frataxin protein and wherein the mRNA is encapsulated within a liposome, wherein the mRNA comprises a polynucleotide sequence that is identical to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO. 3, or SEQ ID NO: 4.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the composition is formulated for intravenous (IV) delivery or intrathecal (IT) delivery.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein the composition comprises mRNA at an amount of at least 1, 2, 3, 4, 5, 10, or 20 μg.

### Claim 4 (depends on 1)

The pharmaceutical composition of claim 1, wherein the mRNA further comprises the 5′ untranslated region (UTR) sequence of SEQ ID NO: 6.

### Claim 5 (depends on 1)

The pharmaceutical composition of claim 1, wherein the mRNA comprises a polynucleotide sequence that is identical to SEQ ID NO: 1.

### Claim 6 (depends on 1)

The pharmaceutical composition of claim 1, wherein the mRNA comprises a polynucleotide sequence that is identical to SEQ ID NO: 2.

### Claim 7 (depends on 1)

The pharmaceutical composition of claim 1, wherein the mRNA comprises a polynucleotide sequence that is identical to SEQ ID NO: 3.

### Claim 8 (depends on 1)

The pharmaceutical composition of claim 1, wherein the mRNA comprises a polynucleotide sequence that is identical to SEQ ID NO: 4.

### Claim 9 (depends on 1)

The pharmaceutical composition of claim 1, wherein the mRNA comprises one or more modified nucleotides selected from the group consisting of pseudouridine, N-1-methy 1-pseudouridine, 2-aminoadenosine, 2-thiothymi dine, pyrrolopyrimidine, 3-methyl adenosine, 5-methylcytidine, C-5 propynyl-cytidine, C-5 propynyl-uridine, 2-aminoadenosine, C5-bromouridine, C5-fluorouri dine, C5-iodouridine, C5-propynyl-uridine, C5-propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8-oxoguanosine, O (6)-methylguanine, 2-thiocyti dine, 1-methyl-adenine, 2-methyl-adenine, 2-methylthio-N-6-isopentenyl-adenine, N6-methyl-adenine, N6-isopentenyl-adenine, 2-thio-cytosine, 3-methyl-cytosine, 4-acetyl-cytosine, 5-methyl-cytosine, 2,6-diaminopurine, 1-methyl-guanine, 2-methyl-guanine, 2,2-dimethyl-guanine, 7-methyl-guanine, 1-methyl-inosine, pseudouracil, dihydrouracil, 2-thio-uracil, 4-thio-uracil, 5-carboxymethylaminomethyl-2-thio-uracil, 5-(carboxyhydroxymethyl)-uracil, 5-fluoro-uracil, 5-bromo-uracil, 5-carboxymethylaminomethyl-uracil, 5-methyl-2-thio-uracil, 5-methyl-uracil, N-uracil-5-oxyacetic acid methyl ester, 5-methylaminomethyl-uracil, 5-methoxyaminomethyl-2-thio-uracil, 5-methoxycarbonylmethyl-uracil, 5-methoxy-uracil, uracil-5-oxyacetic acid methyl ester, uracil-5-oxyacetic acid, 1-methyl-pseudouracil, queosine, beta-D-mannosyl-queosine, wybutoxosine, phosphoramidates, phosphorothioates, methylphosphonates, 7-deazaguanosine, 5-methylcytosine and inosine.

### Claim 10 (depends on 1)

The pharmaceutical composition of claim 1, wherein the liposome comprises one or more cationic lipids, one or more non-cationic lipids, and one or more PEG-modified lipids.

### Claim 11 (depends on 10)

The pharmaceutical composition of claim 10, wherein the one or more cationic lipids comprise a cationic lipid selected from the group consisting of C12-200, MC3, DLinDMA, DLinkC2DMA, cKK-E12, ICE (imidazole cholesterol ester), HGT5000, HGT5001, OF-02, DODAC, DDAB, DMRIE, DOSPA, DOGS, DODAP, DODMA and DMDMA, DODAC, DLenDMA, DMRIE, CLinDMA, CpLinDMA, DMOBA, DOcarbDAP, DLinDAP, DLincarbDAP, DLinCDAP, DLin-K-DMA, DLin-K-XTC2-DMA, HGT4003, and combinations thereof.

### Claim 12 (depends on 10)

The pharmaceutical composition of claim 10, wherein the one or more non-cationic lipids comprise a non-cationic lipid selected from the group consisting of DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine), DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine), DOPE (1,2-dioleyl-sn-glycero-3-phosphoethanolamine), DOPC (1,2-dioleyl-sn-glycero-3-phosphotidylcholine) DPPE (1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine), DMPE (1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine), DOPG dioleoylphosphatidylglycerol) and combinations thereof.

### Claim 13 (depends on 10)

The pharmaceutical composition of claim 10, wherein the liposome further comprises one or more cholesterol-based lipids.

### Claim 14 (depends on 10)

The pharmaceutical composition of claim 10, wherein the liposome further comprises a sphingomyelin.