# US 11,110,130 B2 · Pharmaceutical carriers containing miRNAs for use in the treatment of fibrotic diseases caused by hyperglycemia

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- Number: US 11,110,130 B2
- Document ID: US11110130B2
- Status: Granted
- Kind: B2
- Application number: 16/788,478
- Filed: 2020-02-12
- Published: 2020-07-16
- Granted: 2021-09-07
- Earliest claimed: 2016-05-06
- Assignees: Unicyte Ev AG
- Applicants: Unicyte Ev AG
- Inventors: Maria Felice Brizzi; Giovanni Camussi
- Web page: https://patentgrep.com/patent/US11110130B2

## CPC

- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 31/7105: Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 35/407: Liver; Hepatocytes
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 2310/141: MicroRNAs, miRNAs
- C12N 2320/30: Special therapeutic applications
- 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 invention relates to a new therapeutic application of pharmaceutically acceptable carriers containing miR222. In particular, the invention relates to the use of extracellular vesicles (EVs) which contain the microRNA miR222, in the treatment of fibrotic disease caused by hyperglycaemia, such as diabetic nephropathy and/or renal fibrosis.

## Claims

### Claim 1

A method for treatment of a fibrotic disease caused by hyperglycaemia found in diabetic patients comprising administering to a patient in need thereof a pharmaceutically acceptable carrier carrying microRNA miR222.

### Claim 2 (depends on 1)

The method of claim 1 wherein the pharmaceutically acceptable carrier further carries microRNA miR100.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the pharmaceutically acceptable carrier is a micro- or nanoparticle and wherein the microRNA is contained inside the micro- or nanoparticle or attached to the surface of the micro- or nanoparticle.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the pharmaceutically acceptable carrier is an extracellular vesicle (EV).

### Claim 5 (depends on 1)

The method according to claim 1, wherein the pharmaceutically acceptable carrier is an extracellular vesicle (EV) derived from a stem cell.

### Claim 6 (depends on 5)

The method according to claim 5, wherein the extracellular vesicle (EV) is derived from an adult stem cell.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the extracellular vesicle (EV) is derived from a mesenchymal stem cell (MSC), a non-oval human liver progenitor cell (HLSC) or an adipose stem cell (ASC).

### Claim 8 (depends on 4)

The method according to claim 4, wherein the extracellular vesicle (EV) is a naturally occurring EV or an EV engineered to contain miR222 and optionally miR100.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the extracellular vesicle (EV) is engineered to contain miR222 and miR100.

### Claim 10 (depends on 1)

The method according to claim 1, wherein the fibrotic disease caused by hyperglycaemia found in diabetic patients is selected from the group consisting of diabetic nephropathy, diabetic renal fibrosis, diabetic cardiomyopathy, diabetic non-alcoholic fatty liver, and diabetic retinopathy.

### Claim 11

A method for treatment of a fibrotic disease caused by hyperglycaemia found in diabetic patients comprising administering to a patient in need thereof at least one extracellular vesicle (EV) engineered to contain miR222 or miR100 in an amount between 1×103 and ×105 molecules/EV higher than the amount present in the naturally-occurring extracellular vesicle (EV), wherein the at least one EV is obtainable by loading miR222 or miR100 ex vivo to an extracellular vesicle isolated from a stem cell or body.

### Claim 12 (depends on 11)

The method according to claim 11, wherein the stem cell is an adult stem cell.

### Claim 13 (depends on 12)

The method according to claim 12, wherein the adult stem cell is a mesenchymal stem cell (MSC), a non-oval human liver progenitor cell (HLSC), or an adipose stem cell (ASC).

### Claim 14 (depends on 11)

The method according to claim 11, wherein the fibrotic disease caused by hypoglycaemia found in diabetic patients is selected from the group consisting of diabetic nephropathy, diabetic renal fibrosis, diabetic cardiomyopathy, and diabetic non-alcoholic fatty liver.

### Claim 15 (depends on 10)

The method according to claim 10, wherein the diabetic non-alcoholic fatty liver is NASH.

### Claim 16 (depends on 14)

The method according to claim 14, wherein the diabetic non-alcoholic fatty liver is NASH.
