# US 9,751,938 B2 · Method of inhibiting activation of a T cell by administering an anti-RGM antibody or an RGM siRNA

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- Number: US 9,751,938 B2
- Document ID: US9751938B2
- Status: Granted
- Kind: B2
- Application number: 15/149,314
- Filed: 2016-05-09
- Published: 2016-08-25
- Granted: 2017-09-05
- Earliest claimed: 2009-12-09
- Assignees: Mitsubishi Tanabe Pharma Corporation
- Applicants: Mitsubishi Tanabe Pharma Corporation
- Inventors: Toshihide Yamashita; Takekazu Kubo
- Web page: https://patentgrep.com/patent/US9751938B2

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- A61K 31/07: Retinol compounds, e.g. vitamin A (retinoic acids A61K31/203)
- A61K 31/122: having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
- A61K 31/355: Tocopherols, e.g. vitamin E
- A61K 31/375: Ascorbic acid, i.e. vitamin C; Salts thereof
- A61K 33/00: Medicinal preparations containing inorganic active ingredients
- A61K 33/04: Sulfur, selenium or tellurium; Compounds thereof
- A61K 33/06: Aluminium, calcium or magnesium; Compounds thereof {, e.g. clay}
- A61K 33/26: Iron; Compounds thereof
- A61K 33/30: Zinc; Compounds thereof
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 7/06: Antianaemics
- A61P 17/00: Drugs for dermatological disorders
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/18: against material from animals or humans
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C12N 15/1136: {against growth factors, growth regulators, cytokines, lymphokines or hormones}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/30: Special therapeutic applications
- 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)
- 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

Provided is a T cell activation inhibitor containing an RGM inhibiting substance such as an anti-RGM neutralizing antibody and the like as an active ingredient. The T cell activation inhibitor is useful as a pharmaceutical composition for the prophylaxis or treatment of autoimmune diseases such as multiple sclerosis and the like, and other diseases caused by T cell activation. In addition, a T cell activation inhibiting substance can be screened for by contacting a test substance with RGM and selecting a test substance that lowers the activity level of RGM.

## Claims

### Claim 1

An in vivo method of inhibiting activation of a T cell by a Repulsive Guidance Molecule (RGM) expressing cell, comprising
a step of contacting an RGM inhibiting substance with an RGM expressing cell in a patient that has rheumatism, multiple sclerosis, Guillain-Barré syndrome, neuro-Behcet's disease, malignant anemia, type I (insulin-dependent) diabetes, systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), Sjogren's syndrome, atopic dermatitis, Goodpasture's syndrome, Graves' disease, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, glomerulonephritis, myasthenia gravis, or Hashimoto's disease,
wherein the RGM inhibiting substance is an anti-RGM neutralizing antibody or an RGM siRNA,
thereby inhibiting activation of a T cell by the RGM expressing cell.

### Claim 2 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the RGM inhibiting substance is an anti-RGM neutralizing antibody.

### Claim 3 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the RGM inhibiting substance is an RGM siRNA.

### Claim 4 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has rheumatism.

### Claim 5 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has multiple sclerosis.

### Claim 6 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has Guillain-Barré syndrome.

### Claim 7 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has neuro-Behcet's disease.

### Claim 8 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has malignant anemia.

### Claim 9 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has type I (insulin-dependent) diabetes.

### Claim 10 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has systemic lupus erythematosus (SLE).

### Claim 11 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has inflammatory bowel disease (IBD).

### Claim 12 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has Sjogren's syndrome.

### Claim 13 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has atopic dermatitis.

### Claim 14 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has Goodpasture's syndrome.

### Claim 15 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has Graves' disease.

### Claim 16 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has autoimmune hemolytic anemia.

### Claim 17 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has autoimmune thrombocytopenic purpura.

### Claim 18 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has glomerulonephritis.

### Claim 19 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has myasthenia gravis.

### Claim 20 (depends on 1)

The method of inhibiting activation of a T cell according to claim 1, wherein the patient has Hashimoto's disease.