# US 2013/0172263 A1 · Vh4 codon signature for multiple sclerosis

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- Number: US 2013/0172263 A1
- Document ID: US20130172263A1
- Status: Published application
- Kind: A1
- Application number: 13/789,324
- Filed: 2013-03-07
- Published: 2013-07-04
- Earliest claimed: 2008-07-24
- Assignees: Board of Regents, The University of Texas System
- Inventors: Nancy MONSON
- Web page: https://patentgrep.com/patent/US20130172263A1

## CPC

- C12Q 1/686: Polymerase chain reaction [PCR]
- A61K 38/02: Peptides of undefined number of amino acids; Derivatives thereof
- C12Q 1/6883: for diseases caused by alterations of genetic material
- G01N 33/6896: {Neurological disorders, e.g. Alzheimer's disease}
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/136: Screening for pharmacological compounds
- C12Q 2600/156: Polymorphic or mutational markers
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- 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)
- 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)

## Abstract

The present invention provides for the diagnosis and prediction of multiple sclerosis (MS) in subject utilizing a unique a codon signature in VH4 expressing B cells that has now been associated with MS and not with any other autoimmune disease.

## Claims

### Claim 1

A method for identifying a human subject having or at risk of developing multiple sclerosis (MS) comprising assessing the VH4 structure of a VH4-expressing B-cell from said subject, wherein the presence of a codon signature associated with MS identifies said subject as having or at risk of developing MS.

### Claim 2 (depends on 1)

The method of claim 1, wherein said codon signature comprises a mutation at codon 31B, 56 and/or 81.

### Claim 3 (depends on 2)

The method of claim 2, wherein said codon signature comprises mutations at each of 31B, 56 and 81.

### Claim 4 (depends on 2, 3)

The method of claim 2 or 3, wherein said codon signature further comprises mutations at one or more of codons 32, 40, 57, 60 and 89.

### Claim 5 (depends on 4)

The method of claim 4, wherein said codon signature comprises mutations at each of codons 31B, 32, 40, 56, 57, 60, 81 and 89.

### Claim 6 (depends on 1)

The method of claim 1, wherein said codon signature comprises a mutation at codons 31B, 40, 56, 57, 81 and/or 89.

### Claim 7 (depends on 6)

The method of claim 6, wherein said codon signature comprises a mutation at each of codons 31B, 40, 56, 57, 81 and 89.

### Claim 8 (depends on 1)

The method of claim 1, further comprising assessing one or more traditional MS risk factors.

### Claim 9 (depends on 1)

The method claim 1, wherein assessing comprises sequencing.

### Claim 10 (depends on 1)

The method of claim 1, wherein assessing comprises PCR.

### Claim 11 (depends on 1)

The method of claim 1, wherein said B-cell is obtained from cerebrospinal fluid (CSF).

### Claim 12 (depends on 11)

The method of claim 11, further comprising assessing J chain usage, J chain length and/or CDR3 length.

### Claim 13 (depends on 1)

The method of claim 1, wherein said B-cell is obtained from peripheral blood.

### Claim 14 (depends on 13)

The method of claim 13, further comprising assessing J chain usage, J chain length and/or CDR3 length.

### Claim 15 (depends on 1)

The method of claim 1, further comprising making a treatment decision based on the presence of said codon signature.

### Claim 16

A method of screening for an agent useful in treating multiple sclerosis (MS) comprising:
(a) providing an antibody produced by a VH4-expressing B-cell, said antibody comprising mutations at three or more codons selected from the group consisting of 31B, 32, 40, 56, 57, 60, 81 and 89;
(b) contacting said antibody with a candidate ligand; and
(c) assessing binding of said candidate ligand to said antibody,
wherein binding of said candidate ligand to said antibody identifies said candidate ligand as useful in treating MS.

### Claim 17 (depends on 16)

The method of claim 16, wherein said candidate ligand is a peptide or a peptoid.

### Claim 18

A method of treating a subject having or at risk of developing MS comprising administering to said subject a ligand that binds to an antibody VH-4 antibody comprising mutations at three or more codons selected from the group consisting of 31B, 32, 40, 56, 57, 60, 81 and 89.

### Claim 19 (depends on 18)

The method of claim 18, wherein said ligand is a peptide or a peptoid.

### Claim 20 (depends on 18)

The method of claim 18, wherein said ligand is linked to a toxin or B-cell antagonist.
