# US 2015/0147293 A1 · Uses of interleukin-22(il-22) in treating and preventing nerve damage diseases or neurodegenerative diseases

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- Number: US 2015/0147293 A1
- Document ID: US20150147293A1
- Status: Published application
- Kind: A1
- Application number: 14/369,187
- Filed: 2012-12-27
- Published: 2015-05-28
- Earliest claimed: 2011-12-27
- Assignees: Generon (Shanghai) Corporation Ltd.
- Applicants: Generon ( Shanghai) Corporation LTD.
- Inventors: Dongdong Wu; Zhihua Huang; Heng Liu; Yuliang Huang; Xiaoqiang Yan
- Web page: https://patentgrep.com/patent/US20150147293A1

## CPC

- A61K 38/20: Interleukins [IL]
- A61K 47/55: the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug
- A61K 47/6813: {the drug being a peptidic cytokine, e.g. an interleukin or interferon}
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/14: for treating abnormal movements, e.g. chorea, dyskinesia
- A61P 25/16: Anti-Parkinson drugs
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- 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

## Abstract

This invention discloses the uses of IL-22 in the treatment and prevention of a nerve damage disease or a neurodegenerative disease. In particular, the invention discloses the uses of IL-22 or IL-22 dimers as follows: (i) can protect neurons to recover the functions of injured neurons after ischemic nerve damage in animals in vivo, thus enabling effective treatment of nerve damage diseases, (ii) can significantly inhibit the loss of dopaminergic neurons in substantia nigra in PD model animal, enhance the functions of dopaminergic neurons, significantly reduce neuronal apoptosis in hippocampus, improve learning and memory capacity of AD model rats, and effectively prevent neuronal loss, thereby enabling more effective treatment of neurodegenerative diseases.

## Claims

### Claim 1

A method of treating or preventing a nerve damage disease or a neurodegenerative disease in a subject, comprising administering to the subject an effective amount of an IL-22 or a dimer or multimer thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the nerve damage disease is selected from: stroke, spinal injury, or neurological disorders accompanied with blood brain barrier injury,
and the neurodegenerative disease is selected from: Parkinson's disease (“PD”), Alzheimer's disease (“AD”), Huntington disease, amyotrophic lateral sclerosis, spinal muscular atrophy, primary lateral sclerosis, or spinal cerebellar ataxias.

### Claim 3 (depends on 1)

The method of claim 1, wherein the method comprises administering to the subject an effective amount of an IL-22 dimer, and wherein the IL-22 dimer has a structure represented by Formula I:
M1-L-M2 Formula I
wherein,
M1 is a first monomer of IL-22,
M2 is a second monomer of IL-22,
L is a linker connecting the first monomer and the second monomer and disposed therebetween, and
wherein the IL-22 dimer retains the biological activity of IL-22 and has a serum half-life of longer than twice of that of either the first or the second monomer.

### Claim 4 (depends on 3)

The method of claim 3, wherein the linker L is selected from the group consisting of:
(i) a short peptide comprising 3 to 50 amino acids, and
(ii) a polypeptide of Formula II:
—Z—Y—Z— Formula II
wherein,
Y is a carrier protein,
Z is nothing, or a short peptide comprising 1 to 30 amino acids, and
“—” is a chemical bond or a covalent bond.

### Claim 5 (depends on 3)

The method of claim 3, wherein the first monomer and the second monomer are identical.

### Claim 6 (depends on 3)

The method of claim 3, wherein the biological activity comprises:
(a) activating STAT3 in neurons in vitro,
(b) protecting neurons and reducing the volume of cerebral infarction after ischemic injury in vivo,
(c) activating STAT3 in dopaminergic neurons or hippocampal neurons in vitro,
(d) significantly inhibiting the loss of dopaminergic neurons in substantia nigra in animals of PD model in vivo, or
(e) significantly reducing the apoptosis of neurons in hippocampus in animals of AD model in vivo.

### Claim 7 (depends on 4)

The method of claim 4, wherein the carrier protein is albumin or Fc fragment of human IgG.

### Claim 8 (depends on 1)

The method of claim 1, wherein the method comprises administering to the subject an effective amount of an IL-22 dimer, and wherein the IL-22 dimer is formed by two IL-22 monomers, each comprising an amino acid sequence selected from SEQ ID NOs: 2-5.

### Claim at position 9

9-10. (canceled)

### Claim 11 (depends on 1)

The method of claim 1, wherein the method comprises administering to the subject an effective amount of an IL-22 dimer, wherein the IL-22 dimer is formed by two IL-22 monomers, each comprising IL-22 and an Fc fragment of human IgG.

### Claim 12 (depends on 11)

The method of claim 11, wherein each of the IL-22 monomer comprises amino acids 163-185 of SEQ ID NO:2.

### Claim 13 (depends on 12)

The method of claim 12, wherein each of the IL-22 monomer comprises amino acids 147-385 of SEQ ID NO:2.

### Claim 14 (depends on 12)

The method of claim 12, wherein each of the IL-22 monomer comprises the amino acid sequence of SEQ ID NO:2.

### Claim 15 (depends on 1)

The method of claim 1, wherein the nerve damage disease or neurodegenerative disease is cerebral infarction.

### Claim 16 (depends on 1)

The method of claim 1, wherein the nerve damage disease or neurodegenerative disease is a neurodegenerative disease.

### Claim 17 (depends on 16)

The method of claim 16, wherein the neurodegenerative disease is Parkinson's disease.

### Claim 18 (depends on 16)

The method of claim 16, wherein the neurodegenerative disease is Alzheimer's disease.

### Claim 19 (depends on 1)

The method of claim 1, wherein the subject is human.