# US 10,370,718 B2 · Use of HLA genetic status to assess or select treatment of celiac disease

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- Number: US 10,370,718 B2
- Document ID: US10370718B2
- Status: Granted
- Kind: B2
- Application number: 15/515,185
- Filed: 2015-09-29
- Published: 2017-08-03
- Granted: 2019-08-06
- Earliest claimed: 2014-09-29
- Assignees: ImmusanT, Inc.
- Applicants: ImmusanT, Inc.
- Inventors: Robert P. Anderson
- Web page: https://patentgrep.com/patent/US10370718B2

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- A61K 38/168: {from plants}
- 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}
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/156: Polymorphic or mutational markers
- C12Q 2600/158: Expression markers
- C12Q 2600/16: Primer sets for multiplex assays
- G01N 2800/24: Immunology or allergic disorders
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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

Provided herein are methods of adjusting or selecting a gluten peptide therapy based on the human leukocyte antigen (HLA) genotype, in particular HLA-DQ2.5 homozygosity, of a subject having or suspected of having Celiac disease. Also provided herein are methods of identifying (e.g., diagnosing) a subject, such as a subject having or suspected of having Celiac disease and/or assessing the efficacy of treatment of Celiac disease, e.g. by determining responsiveness to a therapeutic gluten peptide composition or cytokine response, and kits relating thereto.

## Claims

### Claim 1

A method, comprising:
assessing a human leukocyte antigen (HLA) genotype of a subject to determine whether the subject has a homozygous genotype or a heterozygous genotype;
selecting or adjusting a dose of a gluten peptide treatment for the subject based on the HLA genotype of the subject, and
administering the selected or adjusted dose of the gluten peptide treatment to the subject, wherein the subject has or is suspected of having Celiac disease, and
wherein the dose is adjusted or selected for the subject such that the amount is sufficient to provide a therapeutic or physiological effect without causing severe adverse effects.

### Claim 2 (depends on 1)

The method of claim 1,
wherein the assessing comprises determining the sequence of each copy of an HLA-DQA gene and each copy of an HLA-DQB gene in the subject.

### Claim 3 (depends on 2)

The method of claim 2, wherein the determining comprises performing a nucleic-acid based assay on each copy of the HLA-DQA gene, or a portion thereof, and each copy of the HLA-DQB gene, or a portion thereof.

### Claim 4 (depends on 3)

The method of claim 3, wherein the nucleic-acid based assay is a probe-based assay or a sequencing assay.

### Claim 5 (depends on 1)

The method of claim 1, wherein the assessing further comprises identifying the subject as having a homozygous HLA-DQ2.5 genotype or a non-homozygous HLA-DQ2.5 genotype.

### Claim 6 (depends on 5)

The method of claim 5, wherein the non-homozygous HLA-DQ2.5 genotype is a heterozygous HLA-DQ2.5 genotype.

### Claim 7 (depends on 6)

The method of claim 6, wherein the heterozygous HLA-DQ2.5 genotype is HLA-DQ2.5/2.2, HLA-DQ2.5/7, or HLA-DQ2.5/8.

### Claim 8 (depends on 1)

The method of claim 1, wherein the method further comprises:
decreasing a dose of the gluten peptide treatment if the subject has a homozygous HLA-DQ2.5 genotype; or
maintaining or increasing the dose of the gluten peptide treatment if the subject has a non-homozygous HLA-DQ2.5 genotype.

### Claim 9 (depends on 1)

The method of claim 1, wherein the gluten peptide treatment comprises a composition comprising:
a first peptide comprising the amino acid sequence PFPQPELPY (SEQ ID NO:1) and the amino acid sequence PQPELPYPQ (SEQ ID NO:2);
a second peptide comprising the amino acid sequence PFPQPEQPF (SEQ ID NO:3) and the amino acid sequence PQPEQPFPW (SEQ ID NO:4); and
a third peptide comprising the amino acid sequence EQPIPEQPQ (SEQ ID NO:6) and the amino acid sequence PIPEQPQPY (SEQ ID NO:5).

### Claim 10 (depends on 9)

The method of claim 9, wherein the dose is or is decreased to less than 300 micrograms if the subject has a homozygous HLA-DQ2.5 genotype.

### Claim 11 (depends on 10)

The method of claim 10, wherein the dose is or is decreased to less than 150 micrograms if the subject has a homozygous HLA-DQ2.5 genotype.

### Claim 12 (depends on 9)

The method of claim 9, wherein:
the first peptide comprises the amino acid sequence LQPFPQPELPYPQPQ (SEQ ID NO: 62);
the second peptide comprises the amino acid sequence QPFPQPEQPFPWQP (SEQ ID NO: 7); and
the third peptide comprises the amino acid sequence PEQPIPEQPQPYPQQ (SEQ ID NO: 8).

### Claim 13 (depends on 12)

The method of claim 12, wherein:
the first peptide comprises the amino acid sequence ELQPFPQPELPYPQPQ (SEQ ID NO: 9), wherein the N-terminal glutamate is a pyroglutamate and the C-terminal glutamine is amidated;
the second peptide comprises the amino acid sequence EQPFPQPEQPFPWQP (SEQ ID NO:10), wherein the N-terminal glutamate is a pyroglutamate and the C-terminal proline is amidated; and
the third peptide comprises the amino acid sequence EPEQPIPEQPQPYPQQ (SEQ ID NO: 11), wherein the N-terminal glutamate is a pyroglutamate and the C-terminal glutamine is amidated.