# US 2014/0193364 A1 · Tam receptor ligands, metabolites and precursors thereof in the detection and modulation of inflammatory neuropathological disease

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2014/0193364 A1
- Document ID: US20140193364A1
- Status: Published application
- Kind: A1
- Application number: 14/110,685
- Filed: 2012-04-04
- Published: 2014-07-10
- Earliest claimed: 2011-04-08
- Assignees: Howard Florey Institute
- Inventors: Trevor Kilpatrick; Michele Denise Binder; Zhi-Ming Gerry Ma
- Web page: https://patentgrep.com/patent/US20140193364A1

## CPC

- G01N 33/566: using specific carrier or receptor proteins as ligand binding reagents {where possible specific carrier or receptor proteins are classified with their target compounds}
- A61K 38/215: {IFN-beta}
- G01N 33/6863: {Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors}
- G01N 33/86: involving blood coagulating time {or factors, or their receptors}
- G01N 2333/745: Assays involving non-enzymic blood coagulation factors
- G01N 2800/28: Neurological disorders
- G01N 2800/285: Demyelinating diseases; Multipel sclerosis
- G01N 2800/2871: Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event
- G01N 2800/50: Determining the risk of developing a disease
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- 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

The present disclosure relates to the use of TAM receptor ligands, metabolites, precursor and binding partners thereof in the field of inflammatory neuropathology. This includes the early diagnosis and monitoring of an inflammatory neuropathology as well as screening for medicaments used in the treatment and prophylaxis of such a condition. The method comprises screening blood fluid from a subject for a TAM receptor ligand, or metabolite, or precursor thereof wherein an altered level of the ligand or its metabolite or precursor relative to a control is indicative of the presence of an inflammatory neuropathological disease or condition or a likelihood of developing the same. Diagnostic kits, high throughput screening assays and therapeutic compositions for inflammatory neuropathies are also taught herein.

## Claims

### Claim 1

A method for detecting the presence of an inflammatory neuropathological disease or condition in a subject, said method comprising screening blood plasma or other suitable blood fluid from said subject for a TAM receptor ligand or metabolite or precursor thereof wherein an altered level of the ligand or its metabolite or precursor relative to a control is indicative of the presence of an inflammatory neuropathological disease or condition or a likelihood of developing same.

### Claim 2 (depends on 1)

The method of claim 1 wherein the TAM receptor ligand is free ligand.

### Claim 3 (depends on 1)

The method of claim 1 wherein the TAM receptor ligand is Protein S or GAS6 or a metabolite or precursor thereof.

### Claim 4 (depends on 3)

The method of claim 3 wherein the TAM receptor ligand is free Protein S.

### Claim 5 (depends on 1)

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

### Claim 6 (depends on 5)

The method of claim 5 wherein the level of ligand is elevated.

### Claim 7 (depends on 5)

The method of claim 5 wherein the inflammatory neuropathological disease or condition is selected from the group consisting of multiple sclerosis (MS), oligodendrocyte disease, acute disseminated encephalomyelitis, optic neuropathy (including neuromyelitis optic with transient autonomic disturbances), Devic's neuromyelitis optica, tropical spastic paraparesis, non-compressive myelopathies, concentric sclerosis, diffuse sclerosis acute hemorrhagic leukoencephalopathy, metachromatic leukodystrophy, leucoareosis, acute discriminated encephalomyelitis, progressive multifocal leukoencephalopathy, multisystem entrophy and brain trauma resulting in white matter.

### Claim 8 (depends on 7)

The method of claim 7 wherein the inflammatory neuropathological condition or disease is MS, oligodendrocyte disease, stroke or brain trauma.

### Claim 9 (depends on 1)

The method of claim 1 wherein the TAM receptor ligand or is metabolite or precursor is detected by an immunoassay.

### Claim 10 (depends on 9)

The method of claim 9 wherein the immunoassay is a sandwich ELISA.

### Claim 11 (depends on 10)

The method of claim 10 wherein blood plasma or other suitable is contacted with an immobilized antibody or antigen-binding fragment thereof specific for the TAM receptor ligand or its metabolite or precursor for a time and under conditions sufficient for the antibody to capture the ligand and then identifying captured ligand by contacting the captured ligand with an antibody or antigen-binding fragment labeled with a reporter molecule or component of a signal generating pathway or reaction and then detecting the reporter molecule or generated signal.

### Claim 12 (depends on 11)

The method of claim 11 wherein the second antibody or antigen-binding fragment is labeled with an enzyme.

### Claim at position 13

13-23. (canceled)

### Claim 24 (depends on 31)

The method of claim 31, wherein a level of the ligand or metabolite or precursor thereof greater than 105% of the level in a control is indicative of the presence of the inflammatory neuropathological disease or condition or a likelihood of developing same.

### Claim 25 (depends on 24)

The method of claim 24, wherein the TAM receptor ligand is selected from the group consisting of Protein S, GAS6 and a metabolite or precursor thereof.

### Claim 26 (depends on 24)

The method of claim 24, wherein the TAM receptor ligand is selected from the group consisting of Protein S and a metabolite or precursor thereof.

### Claim 27 (depends on 31)

The method of claim 31, wherein a level of the ligand or metabolite or precursor thereof 20% to 95% of the levels in a control is indicative of the presence of the inflammatory neuropathological disease or condition or a likelihood of developing same.

### Claim 28 (depends on 27)

The A method of claim 27, wherein the TAM receptor ligand is selected from the group consisting of Protein S, GAS6 and a metabolite or precursor thereof.

### Claim 29 (depends on 27)

The method of claim 27, wherein the TAM receptor ligand is selected from the group consisting of Protein S and a metabolite or precursor thereof.

### Claim 30

A method for monitoring progression of an inflammatory neuropathological disease or condition in a subject, the method comprising screening blood plasma or other suitable blood fluid in said subject for a TAM receptor ligand or a metabolite or precursor thereof over time wherein a change in levels of ligand within a time period is indicative of disease progression.

### Claim 31

A method for detecting the presence of an inflammatory neuropathological condition or disease or monitoring its progression in a subject, the method comprising screening blood plasma or other suitable blood fluid from said subject for levels of a TAM receptor ligand or a metabolite or precursor thereof, wherein an elevated level of the ligand or a metabolite or precursor thereof compared to a control is indicative of the presence of an inflammatory neuropathological disease or condition or a likelihood of developing same or the continued progression of the disease or condition.

### Claim 32

A method of treating, controlling or preventing development of an inflammatory neuropathological disease or condition, the method comprising measuring the level of a TAM receptor ligand in a subject and comparing the level to a control, the control being a level from a normal, healthy subject or population of subjects or a level from the same subject as being treated taken at an earlier time point, and if the level of the TAM receptor ligand is altered compared to the control administering to the subject an effective amount of an agent selected from the group consisting of:
(i) interferon β or another immunomodulatory agent which influences the clinical course of the inflammatory neuropathological disease or condition;
(ii) an agent which reduces demyelination leading to a reduction in plasma levels of the TAM receptor ligand; and
(iii) an agent which normalizes levels of the TAM receptor ligand while inducing or exacerbating inflammatory neuropathology.