Compositions and methods targeting the Th2 pathway for the treatment of asthma

Patent metadata

Field	Value
Publication number	US-12091708-B2
Application number	US-201816476703-A
Country	US
Kind code	B2
Filing date	Jan 9, 2018
Priority date	Jan 9, 2017
Publication date	Sep 17, 2024
Grant date	Sep 17, 2024

Abstract

Compositions and methods for diagnosing and treating asthma and asthma patients a Th2 high asthma phenotype are disclosed.

First claim

What is claimed is:

1. A method for detecting and treating asthma with a Th2 high molecular phenotype in a human asthma patient, the method comprising;
a) obtaining a biological sample comprising nucleic acids from the human asthma patient;
b) detecting in said sample, that the nucleic acids harbor a combination of single nucleotide polymorphisms (SNPs): a C at rs2786098 together with a G at rs2014202, said detecting of the combination indicating that said patient has asthma with a Th2 high molecular phenotype; and
c) following said detecting, administering to the patient at least one CRTH2 inhibitor that targets the Th2 inflammation pathway selected from ACT-453859, ACT-463036, ADC-3680, ADC7405, ADC-9971, AM-211, AM-461, AMG-009, AP768, AP 770, AP761, ARRY-005, ARRY-006, ARRY-502, ATX-2286, ATX-2417, AZD-1981, AZD-5985, AZD-9075, BBI-5000, BI-1021958, BI 1060469, BI-671800, thienopyrrole acetic acids, isoquinoline CRTH1 antagonist, SOA-002, 3-indolyl sultams, AM156, AM206, CT133, fevipiprant, IW-1221, MK-1029, KBP-7026, NVP-QAV680, RG-7185, SAR398171, setipiprant, timapiprant, TM-30510, and vidupiprant
wherein said SNPs in said combination are detected by performing a process selected from detection of specific hybridization, measurement of allele size, restriction fragment length polymorphism analysis, allele-specific hybridization analysis, single base primer extension reaction, and sequencing of an amplified polynucleotide.

2. The method of claim 1 , further comprising detecting in said sample that the nucleic acids harbor one or more single nucleotide polymorphism (SNP) having rs numbers selected from a G at rs7522056, an A at rs6673687, a C at rs11240565, a C at rs11240554, a G at rs823116, an A at rs1775146, a C at rs1775143, a T at rs12565321, and a C at rs12567894.

3. The method as claimed in claim 1 , wherein the nucleic acids are amplified prior to detection of the SNPs in the combination.

4. The method of claim 1 , wherein the nucleic acids are obtained from isolated cells from the human patient.

5. A method for treating asthma comprising;
a) obtaining a biological sample comprising nucleic acids from a human patient, or obtaining genetic information from a human patient;
b) detecting in the sample, or determining from the genetic information, that a combination of single nucleotide polymorphisms (SNPs), a C at rs2786098 together with a G at rs2014202, is present in said human patient; and
c) following step (b), administering to said human patient an agent that targets the Th2 inflammation pathway.

6. The method of claim 5 , further comprising detecting in said sample that the nucleic acids harbor one or more single nucleotide polymorphism (SNP) having rs numbers selected from a G at rs7522056, an A at rs6673687, a C at rs11240565, a C at rs11240554, a G at rs823116, an A at rs1775146, a C at rs1775143, a T at rs12565321, and a C at rs12567894.

7. The method of claim 6 , wherein said agent is selected from CRTH2 inhibitors ACT-453859, ACT-463036, ADC-3680, ADC7405, ADC-9971, AM-211, AM-461, AMG-009, AP768, AP 770, AP761, ARRY-005, ARRY-006, ARRY-502, ATX-2286, ATX-2417, AZD-1981, AZD-5985, AZD-9075, BBI-5000, BI-1021958, BI 1060469, BI-671800, thienopyrrole acetic acids, isoquinoline CRTH1 antagonist, SOA-002, 3-indolyl sultams, AM156, AM206, CT133, fevipiprant, IW-1221, MK-1029, KBP-7026, NVP-QAV680, RG-7185, SAR398171, setipiprant, timapiprant, TM-30510, and vidupiprant.

8. A method for treating Th2 high molecular phenotype asthma in a human patient, comprising,
a) obtaining a biological sample comprising nucleic acids from a human subject, or obtaining genetic information relating to the human patient;
b) detecting in the sample, or determining from the genetic information, that the human patient has: a C at rs2786098 together with a G at rs2014202; and
c) following b), administering an effective amount of one or more agents that target the Th2 inflammation pathway thereby treating Th2-high asthma wherein said one or more agents is selected from ACT-453859, ACT-463036, ADC-3680, ADC7405, ADC-9971, AM-211, AM-461, AMG-009, AP768, AP 770, AP761, ARRY-005, ARRY-006, ARRY-502, ATX-2286, ATX-2417, AZD-1981, AZD-5985, AZD-9075, BBI-5000, BI-1021958, BI 1060469, BI-671800, thienopyrrole acetic acids, isoquinoline CRTH1 antagonist, SOA-002, 3-indolyl sultams, AM156, AM206, CT133, fevipiprant, IW-1221, MK-1029, KBP-7026, NVP-QAV680, RG-7185, SAR398171, setipiprant, timapiprant, TM-30510, and vidupiprant.

9. The method of claim 8 , wherein said one or more agents includes AP768 or AP770.

10. The method of claim 8 , further comprising detecting in said sample that the nucleic acids harbor one or more single nucleotide polymorphism (SNP) having rs numbers selected from a G at rs7522056, an A at rs6673687, a C at rs11240565, a C at rs11240554, a G at rs823116, an A at rs1775146, a C at rs1775143, a T at rs12565321, and a C at rs12567894.

Assignees

• Childrens Hospital Philadelphia

Inventors

• Hakonarson Hakon
• Sleiman Patrick

Classifications

• C12Q1/6883

  for diseases caused by alterations of genetic material · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• G01N2800/122

  Chronic or obstructive airway disorders, e.g. asthma COPD · CPC title

• C12Q1/6827 Primary

  for detection of mutation or polymorphism · CPC title