IP Library Granted Patent US 11,795,496
Granted Patent B2
US 11,795,496 · App. 15/738,457 · Granted Oct 24, 2023

Epigenetic chromosome interactions

Inventors: Aroul Ramadass (Oxford, GB); Ewan Hunter (Oxford, GB); Alexandre Akoulitchev (Oxford, GB)
Assignee: Oxford Biodynamics PLC
C12Q1/6827C12Q1/6883C12Q1/6886G16B40/00G16H50/70C12Q2521/501C12Q2523/101C12Q2537/159C12Q2600/106
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Quick Facts
Patent No.
US 11,795,496
App. No.
15/738,457
Granted
Oct 24, 2023
Kind
B2
Abstract

A method of determining responsiveness to therapy for rheumatoid arthritis.

Claims (20)

1. A method of selecting a human subject and treating the selected human subject, wherein the selected human subject is responsive to a specific therapy for rheumatoid arthritis and is in need of therapy for rheumatoid arthritis, and wherein the method comprises detecting the presence or absence of a first, second, third, fourth and fifth chromosomal interaction in a sample from the human subject, wherein selecting the human subject as responsive to the specific therapy is based on detection of:

the absence of a first chromosomal interaction,

the presence of a second chromosomal interaction,

the absence of a third chromosomal interaction,

the presence of a fourth chromosomal interaction, and

the presence of a fifth chromosomal interaction;

and treating the selected human subject for rheumatoid arthritis by administering to the selected human subject the specific therapy,

wherein said detecting is carried out by

(a) cross-linking of chromosome regions in the sample from the human subject which have come together in a chromosome interaction;

(b) subjecting said cross-linked regions to cleavage;

(c) ligating said cross-linked cleaved DNA ends to form ligated nucleic acids; and

(d) detecting the presence or absence of the ligated nucleic acids to thereby detect

whether regions have been brought together in a chromosome interaction;

wherein:

the first chromosomal interaction is on chromosome 4 in the CXCL13 gene and the ligated nucleic acid corresponding to the first chromosomal interaction is detected by the probe sequence: TTATATCTCCTACCTCCAAGCCTGGCAGTCGATTCCAAAGTGAAGCAAAAAAAAAAC TTC (SEQ ID NO: 99),

the second chromosomal interaction is on chromosome 21 in the IFNAR1 gene and the ligated nucleic acid corresponding to the second chromosomal interaction is detected by the probe sequence: GTGCAGAGCGAGAGCGGGGCAGAGGCGGTCGAAACTGGGAGAATTCATCTGAAAT GATTA (SEQ ID NO: 75),

the third chromosomal interaction is on chromosome 6 in the IL-17A gene and the ligated nucleic acid corresponding to the third chromosomal interaction is detected by the probe sequence: CCCTCCCTCAACATGCAGGGATTACAATTCGAAGATGGTCTGAAGGAAGCAATTGG GAAA (SEQ ID NO: 103),

the fourth chromosomal interaction is on chromosome 16 in the IL-21R gene and the ligated nucleic acid corresponding to the fourth chromosomal interaction is detected by the probe sequence: GAGGCAGGCAGATCATGAGGTCAGGAGTTCGAGCCCTGGACCCCAGGCCAGCTAAT GAGG (SEQ ID NO: 76), and

the fifth chromosomal interaction is on chromosome 12 in the IL-23 gene and the ligated nucleic acid corresponding to the fifth chromosomal interaction is detected by the probe sequence: AGTGGCATGATCACAGCTCACTGCCACCTCGAAACCAAACCCTGTGACTTCAACACC CAA (SEQ ID NO: 102),

and wherein the specific therapy comprises methotrexate or a pharmaceutically acceptable salt thereof.

Assignments (1)
CHANGE OF NAME Recorded Mar 24, 2022
From: OXFORD BIODYNAMICS LIMITED
To: OXFORD BIODYNAMICS PLC
Reel/Frame 059495/0868 →
Priority Claims (3)
GB 1511079 · Jun 24, 2015 · national
GB 1511080 · Jun 24, 2015 · national
GB 1519555 · Nov 5, 2015 · national
Continuity (1)
Related Publication 20190071715A1 · Mar 7, 2019