# US 2010/0168210 A1 · T-Cell Cytokine-Inducing Surface Molecules and Methods of Use

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- Number: US 2010/0168210 A1
- Document ID: US20100168210A1
- Status: Published application
- Kind: A1
- Application number: 12/663,328
- Filed: 2008-06-05
- Published: 2010-07-01
- Earliest claimed: 2007-06-05
- Inventors: Carl Keith Edwards, III; Li Li; Karen R. Jonscher; David Norris
- Web page: https://patentgrep.com/patent/US20100168210A1

## CPC

- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/4015: having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
- A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
- A61K 31/4406: only substituted in position 3, e.g. zimeldine (nicotinic acid A61K31/455)
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 5/16: for decreasing, blocking or antagonising the activity of the thyroid hormones
- A61P 11/06: Antiasthmatics
- A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers
- A61P 17/06: Antipsoriatics
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- 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 31/12: Antivirals
- A61P 31/18: for HIV
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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

## Abstract

The invention provides cytokine modulators and methods for using the same to modulate cytokine production in monocyte lineage-derived cells. In particular, cytokine modulators of the invention selectively bind to a T-cell cytokine-inducing surface molecule (TCISM)-ligand of T lymphocytes or the corresponding TCISM-receptor of monocyte lineage-derived cells, thereby modulating cytokine production in monocyte lineage-derived cells.

## Claims

### Claim 1

A method for modulating cytokine production in monocyte lineage-derived cells of a subject comprising administering a cytokine modulator to said subject, wherein the cytokine modulator selectively binds to a T-cell cytokine-inducing surface molecule (TCISM)-ligand of a T lymphocyte or the corresponding TCISM-receptor of a monocyte lineage-derived cell, whereby binding of the cytokine modulator to the TCISM-ligand or the TCISM-receptor modulates cytokine production in monocyte lineage-derived cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein the TCISM-ligand comprises at least one of the TCISM-ligand listed in Table 1.

### Claim 3 (depends on 2)

The method of claim 2, wherein TCISM-ligand comprises CD81, CD21, CD316, α-Enolase, FKBP4, other members of the FKBP multigene family, or a combination thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein monocyte lineage-derived cells comprise monocyte lineage-derived macrophages, antigen-presenting cells (APC), dendritic cells, Langerhans cells, Kuppfer Cells, or a combination thereof.

### Claim 5 (depends on 1)

The method of claim 1, wherein the T lymphocyte is CD3+ T lymphocyte.

### Claim 6 (depends on 1)

The method of claim 1, wherein the modulated cytokine comprises Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-32 (IL-32), or a combination thereof.

### Claim 7 (depends on 1)

The method of claim 1, wherein TCISM-ligand is a TCISM-ligand that is present on a CD3+ lymphocyte.

### Claim 8 (depends on 7)

The method of claim 7, wherein TCISM-ligand comprises CD81, CD21, CD315, CD316, α-Enolase, FKBP, or a combination thereof.

### Claim 9 (depends on 1)

The method of claim 1, wherein the TCISM-receptor comprises a TCISM-receptor that is present on a CD68+ antigen-presenting cell.

### Claim 10 (depends on 9)

The method of claim 9, wherein the TCISM-receptor comprises a receptor for CD81, a receptor for CD21, a receptor for CD315, a receptor for CD316, a receptor for α-Enolase, a receptor for FK binding protein, or a combination thereof.

### Claim 11 (depends on 10)

The method of claim 10, wherein the TCISM-receptor comprises a receptor for a TCISM-ligand that is present on CD19, CD21, CD225, CD315, CD316, C3dR, CD19, CD81, BCR, CD9, CD81, KAI1/CD82, or a combination thereof.

### Claim 12

A method for treating a clinical condition mediated by acute or chronic inflammation in a subject comprising administering a cytokine modulator to said subject, wherein the cytokine modulator selectively binds to a T-cell cytokine-inducing surface molecule (TCISM)-ligand of T lymphocytes or the corresponding TCISM-receptor of monocyte lineage-derived cells, whereby modulation of cytokine production by the cytokine modulator is used to treat the clinical condition mediated by acute or chronic inflammation.

### Claim 13 (depends on 12)

The method of claim 12, wherein the cytokine modulator binds selectively to a TCISM-ligand that is present on the surface of CD3+ lymphocytes.

### Claim 14 (depends on 12)

The method of claim 12, wherein the cytokine modulator binds selectively to a TCISM-receptor that is present on the surface of a CD68+ monocytic cell.

### Claim 15 (depends on 12)

The method of claim 12, wherein the clinical condition comprises an autoimmune disease.

### Claim 16 (depends on 15)

The method of claim 15, wherein the T-lymphocyte-mediated autoimmune disease comprises Rheumatoid Arthritis, Multiple Sclerosis, Crohn's Disease, Psoriasis, Psoriatic Arthritis, Graves Disease, Autoimmune Polyendocrine Syndromes, Hereditary Proteinuria Syndrome, Type I Diabetes, Systemic Lupus Erythematosus, Primary Bilary Cirrhosis, Autoimmune Thyroiditis, Hepatitis, Acquired Immunodeficiency Disease (HIV), Graft versus Host Disease, Allograft Disease, Asthma, or a combination thereof.

### Claim 17 (depends on 12)

The method of claim 12, wherein the clinical condition comprises cancer.

### Claim 18 (depends on 12)

The method of claim 12, wherein the clinical condition comprises a Cutaneous T-Cell Lymphoma, HTLV-I-Associated Cutaneous T-Cell Lymphoma, HTLV-II-Associated Lymphoma, Hairy Cell Leukemia, Idiopathic CD4+ T-Lymphocytopenia, Melanoma, or a combination thereof.

### Claim 19

A method for treating an autoimmune disease in a subject comprising administering a therapeutically effective amount of an antagonist to a TCISM-ligand or an antagonist to the corresponding TCISM-receptor to the subject in need of such treatment.

### Claim 20

A method for modulating cytokine production in monocyte lineage-derived cells of a subject comprising administering a siRNA to said subject, wherein the siRNA inhibits transcription of a gene for a T-cell cytokine-inducing surface molecule (TCISM)-ligand of a T lymphocyte, whereby inhibition of transcription of the TCISM-ligand reduces cytokine production in the subject.