# US 12,006,547 B2 · Detection of chromosome interactions as indicative of amyotrophic lateral sclerosis

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- Number: US 12,006,547 B2
- Document ID: US12006547B2
- Status: Granted
- Kind: B2
- Application number: 16/652,959
- Filed: 2018-10-01
- Published: 2020-12-31
- Granted: 2024-06-11
- Earliest claimed: 2017-10-02
- Assignees: Oxford Biodynamics PLC
- Applicants: Oxford BioDynamics PLC
- Inventors: Alexandre Akoulitchev; Aroul Selvam Ramadass; Ewan Hunter; Matthew Salter
- Web page: https://patentgrep.com/patent/US12006547B2

## CPC

- C12Q 1/6883: for diseases caused by alterations of genetic material
- C12Q 1/6827: for detection of mutation or polymorphism
- 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 2600/178: miRNA, siRNA or ncRNA
- 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

## Abstract

A process for analysing chromosome regions and interactions relating to ALS and Huntington's disease.

## Claims

### Claim 1

A process for selecting a human individual and treating the selected human individual, wherein the selected human individual is in need of therapy for amyotrophic lateral sclerosis (ALS), wherein selecting the human individual is by:
detecting the absence of a first chromosome interaction,
detecting the presence of a second chromosome interaction,
detecting the presence of a third chromosome interaction,
detecting the presence of a fourth chromosome interaction,
detecting the presence of a fifth chromosome interaction,
detecting the absence of a sixth chromosome interaction,
detecting the absence of a seventh chromosome interaction,
detecting the absence of an eighth chromosome interaction,
detecting the presence of a ninth chromosome interaction,
detecting the absence of a tenth chromosome interaction,
detecting the absence of an eleventh chromosome interaction,
detecting the absence of a twelfth chromosome interaction,
detecting the presence of a thirteenth chromosome interaction,
detecting the presence of a fourteenth chromosome interaction,
detecting the presence of a fifteenth chromosome interaction,
detecting the presence of a sixteenth chromosome interaction, and
detecting the presence of a seventeenth chromosome interaction
in a sample from the human individual;
and treating the selected human individual for amyotrophic lateral sclerosis (ALS) by administering an agent which is therapeutic for amyotrophic lateral sclerosis (ALS);
wherein said detecting comprises:
(i) cross-linking of chromosome regions which have come together in a chromosome interaction;
(ii) subjecting said cross-linked regions to cleavage to form cross-linked cleaved nucleic acid;
(iii) ligating said cross-linked cleaved nucleic acid ends to form ligated nucleic acid; and
(iv) detecting the presence or absence of the ligated nucleic acid;
wherein:
the ligated nucleic acid corresponding to the first chromosome interaction is detected by the probe sequence
(SEQ ID NO: 2)
TCACCACACATCACCCCCTTGCTCCTCCTCGAGTCTTGGTGACCACAAC
AGGGTGCCACC,
the ligated nucleic acid corresponding to the second chromosome interaction is detected by the probe sequence
(SEQ ID NO: 3)
GAGGTGGGTGAATCATGAGGTCAAGGGTTCGACAATAGTTGAGAATCTC
CAACCACCTGG,
the ligated nucleic acid corresponding to the third chromosome interaction is detected by the probe sequence
(SEQ ID NO: 4)
GGCCTTATAGTCAGCTGATCAGGTGAAATCGATTGGTCCTTAGGATCAGC
TACCATTTGC,
the ligated nucleic acid corresponding to the fourth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 5)
GAGGCAGGCGGATCACAAAGTCAAAAGATCGATAACTTCAATAATAGTTA
CAGATGCAAA,
the ligated nucleic acid corresponding to the fifth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 6)
AGCACCATATCTGGGATGTAGCTATTGCTCGAGATTGCAGTGAGCTGTGA
TCACACCTCT,
the ligated nucleic acid corresponding to the sixth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 7)
TCTTCCCTCTTTTTAAAACCACCATTCATCGACCCCACACATCCTGTGCC
ACTCTACTGC,
the ligated nucleic acid corresponding to the seventh chromosome interaction is detected by the probe sequence
(SEQ ID NO: 8)
TAACCATTATGCATCACTAACATAGCATTCGATATGATATGCTCAGTTTA
GTTAGGGAAA,
the ligated nucleic acid corresponding to the eighth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 9)
GGCTCAGGAAGAGAACTATTTGTCTCTTTCGACACGCACATGCAGGACAC
TCACACGTAG,
the ligated nucleic acid corresponding to the ninth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 10)
GTTGGGTGGATCCCTTGAGCTCAGGAATTCGAAGAATGATTTTTCAGCCC
GTGTGGAAGG,
the ligated nucleic acid corresponding to the tenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 11)
ATCAAAAGAAAATAGATACTTGTCTTACTCGAGTTGAATAAAATCCTCAG
CTTTCTGTCC,
the ligated nucleic acid corresponding to the eleventh chromosome interaction is detected by the probe sequence
(SEQ ID NO: 12)
AAAAGAAACTGTGAAAAGTTGTCACATTTCGATTAAATCCAAAAAGGTCT
TCTATGAGGC,
the ligated nucleic acid corresponding to the twelfth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 13)
TTAAAAGTATAGTAGTTGGCATTAACATTCGACCTTTTTCTGTTTCAGTA
ACCAACCCAG,
the ligated nucleic acid corresponding to the thirteenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 14)
CATCAACTAATAGTTAAACATTATAATATCGACTGAAGACCTTTCATACT
GTAAGATTCA,
the ligated nucleic acid corresponding to the fourteenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 15)
CATCAACTAATAGTTAAACATTATAATATCGAGTCTGCAGTGAGCTGAGA
TCACACTGCC,
the ligated nucleic acid corresponding to the fifteenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 16)
TTATTCCTTTCCAAATAGTTAAAATTATTCGAAACTTTTAAGAATCAATA
TAAAATTTCC,
the ligated nucleic acid corresponding to the sixteenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 17)
CATAATTATAAATTAAAAAATGACACTATCGATTATGTCCAGTGTTTCTT
GGTTGGTGTC,
and
the ligated nucleic acid corresponding to the seventeenth chromosome interaction is detected by the probe sequence
(SEQ ID NO: 18)
CAGAGCACTAAGATAGACTTCTAAGGTTTCGAGGCATATAGCTCCAGCTG
TATTGAGGTA.

### Claim 2 (depends on 1)

The process according to claim 1 wherein the detecting comprises specific detection of the ligated nucleic acid by quantitative PCR (qPCR), wherein the probe comprises:
a fluorophore covalently attached to the 5′ end of the probe, and/or
a quencher covalently attached to the 3′ end of the probe.