# US 9,518,104 B2 · Compositions and methods for treating multiple sclerosis

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- Number: US 9,518,104 B2
- Document ID: US9518104B2
- Status: Granted
- Kind: B2
- Application number: 14/370,515
- Filed: 2013-01-04
- Published: 2014-12-25
- Granted: 2016-12-13
- Earliest claimed: 2012-01-05
- Assignees: Centre for Addiction and Mental Health
- Applicants: Centre for Addiction and Mental Health
- Inventors: Fang Liu
- Web page: https://patentgrep.com/patent/US9518104B2

## CPC

- C07K 14/70571: {for neuromediators, e.g. serotonin receptor, dopamine receptor}
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- 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 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2319/00: Fusion polypeptide
- C07K 2319/10: containing a tag for extracellular membrane crossing, e.g. TAT or VP22
- C07K 2319/23: containing a GST-tag
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

Disclosed are polypeptides, compositions and methods for the treatment or prophylaxis of multiple sclerosis. The method involves the steps of administering a polypeptide, or nucleic acid encoding the polypeptide, comprising the GluR2 NTal-3-2 (Y142-K172) amino acid sequence as shown by SEQ ID NO:1 or SEQ ID NO:5 to a subject in need of the treatment.

## Claims

### Claim 1

A method for supressing macrophage infiltration, microglia activation or infiltration of leukocytes in the central nervous system (CNS) of a subject that exhibits multiple sclerosis-like symptoms of axonal damage, oligodendrocyte death, demyelination or a combination thereof comprising administering a polypeptide (a) comprising Asp153-Lys172 of the GluR2 N-terminus (DSDRGLSTLQAVLDSAAEKK (SEQ ID NO:5)) and wherein the polypeptide does not comprise SEQ ID NO:1 or (b) of between 31 and 200 amino acids comprising a GluR2 NT1-3-2 (Y142-K172) amino acid sequence defined by SEQ ID NO:1 to the subject to suppress macrophage infiltration, microglia activation or infiltration of leukocytes in the CNS of the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein said polypeptide consists of SEQ ID NO:1 or SEQ ID NO:5.

### Claim 3 (depends on 1)

The method of claim 1, wherein said polypeptide is covalently attached to a heterologous polypeptide, to form a fusion protein.

### Claim 4 (depends on 3)

The method of claim 3, wherein said fusion protein comprises a protein transduction domain.

### Claim 5 (depends on 3)

The method of claim 3, wherein said heterologous polypeptide does not encompass a GluR2 subunit sequence.

### Claim 6 (depends on 1)

The method of claim 1, wherein said polypeptide is attached covalently or non-covalently to a non-protein substrate, non-protein molecule, non-protein macromolecule, or any combination thereof.

### Claim 7 (depends on 6)

The method of claim 6, wherein the polypeptide, non-protein substrate, non-protein molecule, non-protein macromolecule, or any combination thereof is labelled.

### Claim 8 (depends on 1)

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

### Claim 9 (depends on 1)

The method of claim 1, wherein the polypeptide is administered in the form of a composition comprising the polypeptide and a pharmaceutically acceptable carrier, diluent, or excipient.

### Claim 10 (depends on 1)

The method of claim 1 wherein the subject exhibits demyelination.

### Claim 11

A method for supressing macrophage infiltration, microglia activation or infiltration of leukocytes in the central nervous system (CNS) of a subject that exhibits multiple sclerosis-like symptoms of axonal damage, oligodendrocyte death, demyelination or a combination thereof comprising administering a composition comprising a polypeptide (a) comprising Asp153-Lys172 of the GluR2 N-terminus (DSDRGLSTLQAVLDSAAEKK (SEQ ID NO:5)) and wherein the polypeptide does not comprise SEQ ID NO:1 or (b) of between 31 and 200 amino acids comprising a GluR2 NT1-3-2 (Y142-K172) amino acid sequence defined by SEQ ID NO:1 to the subject to suppress macrophage infiltration, microglia activation or infiltration of leukocytes in the CNS of the subject.

### Claim 12 (depends on 11)

The method of claim 11, wherein said polypeptide consists of SEQ ID NO:1 or SEQ ID NO:5.

### Claim 13 (depends on 11)

The method of claim 11, wherein said polypeptide is covalently attached to a heterologous polypeptide, to form a fusion protein.

### Claim 14 (depends on 13)

The method of claim 13, wherein said fusion protein comprises a protein transduction domain.

### Claim 15 (depends on 13)

The method of claim 13, wherein said heterologous polypeptide does not encompass a GluR2 subunit sequence.

### Claim 16 (depends on 11)

The method of claim 11, wherein said polypeptide is attached covalently or non-covalently to a non-protein substrate, non-protein molecule, non-protein macromolecule, or any combination thereof.

### Claim 17 (depends on 16)

The method of claim 16, wherein the polypeptide, non-protein substrate, non-protein molecule, non-protein macromolecule, or any combination thereof is labelled.

### Claim 18 (depends on 16)

The method of claim 16, wherein said polypeptide consists of SEQ ID NO:1 or SEQ ID NO:5.

### Claim 19 (depends on 11)

The method of claim 11, wherein the subject is a human.

### Claim 20 (depends on 11)

The method of claim 11, wherein the composition further comprises a pharmaceutically acceptable carrier, diluent, or excipient.

### Claim 21

A method for supressing macrophage infiltration, microglia activation or infiltration of leukocytes in the central nervous system (CNS) of a subject that exhibits multiple sclerosis-like symptoms of axonal damage, oligodendrocyte death, demyelination or a combination thereof comprising administering a polypeptide (a) comprising Asp153-Lys172 of the GluR2 N-terminus (DSDRGLSTLQAVLDSAAEKK (SEQ ID NO:5)) and wherein the polypeptide does not comprise SEQ ID NO:1 or (b) of between 31 and 200 amino acids comprising a GluR2 NT1-3-2 (Y142-K172) amino acid sequence defined by SEQ ID NO:1 to the subject to suppress macrophage infiltration, microglia activation or infiltration of leukocytes in the CNS of the subject, and wherein the method increases neuronal survival in the subject.